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CD003390

The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.

5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)

CD002830

This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.

Droperidol in acutely agitated patients. A double-blind placebo-controlled study.

Forty-one acutely agitated patients received an i.v. injection of 4 ml of a double blind solution containing either 10 mg of droperidol or placebo. The need for further medication (5 mg of haloperidol after 3 minutes or individually adapted psychotropics after 30 minutes) was used as a parameter for the evaluation of the results. Three minutes after the injection, haloperidol was needed by only six out of 19 patients of the droperidol group, but by 19 patients of the control group. Thirty minutes after the first injection, further medication was needed by only four droperidol patients and 10 placebo patients. No side effects could be attributed to the double blind medication.

CD002830

This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.

Droperidol vs. haloperidol in the initial management of acutely agitated patients.

In a double-blind clinical study, 27 acutely agitated patients were treated with an intramuscular injection of 5 mg of droperidol or 5 mg of haloperidol from identical appearing vials. At 30 minutes following treatment, 81% of the patients treated with haloperidol but only 36% treated with droperidol required a second injection (p less than .05). Thus, droperidol, a safe butyrophenone neuroleptic, appears to be a drug of choice for rapid and reliable control of acute agitation.

CD002830

This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.

[Droperidol: a double-blind clinical study].

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Evaluation of the effectiveness of a low sodium diet in the treatment of mild to moderate hypertension.

28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial, but who were otherwise unselected, took part in a randomised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package. The general health package did not include any specific hypotensive procedures. Changes in blood pressure were measured at predetermined intervals over the course of a year. Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year, but there was no significant difference between the groups. It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Effects of a low-salt diet and of acute salt loading on blood pressure and intralymphocytic sodium concentration in young subjects with borderline hypertension.

1. Three groups of young patients with borderline hypertension were studied for a 12 months period. The first was on a free sodium diet while the second was on a low-salt diet. The third group of patients underwent acute salt loading. 2. After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted. Five patients who were re-checked after 24 months also had a significant increase in blood pressure. 3. Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure. 4. After acute salt loading, borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

A pilot study to test the feasibility of salt restriction in a community.

Index subjects were selected from the population of Milton studied in the May 1981 survey. Index subjects aged 64 or less with a systolic blood pressure 138-179 mmHg (18.35/23.8 kPa), including those on antihypertensive treatment, were invited to participate with their families. Index subjects were divided into two matched groups. One group was randomly assigned to be the control group and the other to be the salt-restriction group. Age, weight, height and 24-hour urinary excretion of sodium, potassium and creatinine at the start of the study in August 1981 were similar for the control and salt-restriction groups. When tested in November 1981, the salt-restriction group had achieved a reduction in 24-hour sodium excretion to a mean of 84 mmol for men and 70 mmol for women; corresponding values for the control groups were 150 and 120 mmol. A further test in March 1982 showed little further change. Potassium output changed very little. Attitudes to the low-salt diet varied, but 87 percent found it tolerable or actually preferable. There is no doubt that major reductions in sodium intake are feasible. However, if these are to be achieved on a large scale, food, manufacturers will need to offer a variety of low-sodium foods.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

The Hypertension Prevention Trial: three-year effects of dietary changes on blood pressure. Hypertension Prevention Trial Research Group.

A total of 841 healthy men and women aged 25 to 49 years, with diastolic blood pressures of 78 to 89 mm Hg, were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary counseling treatment groups (reduced calories, reduced sodium, reduced sodium and calories, or reduced sodium and increased potassium). Participants were followed for a 3-year period to assess the effect of dietary changes on blood pressure. After 6 months, counseling had resulted in a net (of control) mean overnight urinary sodium reduction of 13%, a potassium increase of 8%, and a decrease in mean body weight of 7%. At 3 years, the sodium and weight reductions were 10% and 4%, respectively; the potassium change was nil. All four dietary counseling treatment groups had lower mean blood pressures than the control group. The largest net reduction in blood pressure occurred in the calorie group: diastolic pressure was 2.8 mm Hg and 1.8 mm Hg and systolic pressure, 5.1 mm Hg and 2.4 mm Hg at 6 months and 3 years, respectively. All four dietary counseling treatment groups experienced fewer hypertensive events; significantly fewer occurred in the sodium groups. The beneficial effects on blood pressure achieved in this trial have implications for the prevention of cardiovascular disease through dietary reduction of calories and sodium.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Sodium restriction can delay the return of hypertension in patients previously well-controlled on drug therapy.

Sodium restriction can reduce blood pressure in hypertensive patients. The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake. The present paper demonstrates that in such patients on a normal salt diet, 90% become hypertensive within 6 months while only 40% of people on a reduced sodium diet become hypertensive. It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Feasibility of a long-term low-sodium diet in mild hypertension.

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Salt restriction and physical activity in treated hypertensives.

To determine the effect on blood pressure from brisk walking with or without salt restriction in a community based sample of treated hypertensives. The intervention was undertaken in a community setting with a factorial randomised controlled trial and blinded assessment of blood pressure. One hundred and eighty one healthy adult volunteers with a sedentary lifestyle and on pharmacological therapy for hypertension briskly walked for 40 minutes three times per week with or without salt restriction. Systolic and diastolic blood pressure were assessed at three and six months. Of the original 208 participants 181 (87%) completed the study. significant reductions of up to 7 mm Hg were found in systolic blood pressure at 3 months for brisk walking alone (p = 0.04) and salt restriction alone (p = 0.03) but not for the combined intervention (p = 0.17). No significant change was found for diastolic blood pressure. There was no significant change in blood pressure at 6 months. Simple advice on exercise and sodium restriction in a community setting can significantly lower systolic blood pressure at least for 3 months. The combination of the two interventions was less effective than each therapy alone.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I.

To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure. Randomized control multicenter trials. Volunteers recruited from the community, treated and followed up at special clinics. Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements. Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months. Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures. Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05). Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group.

Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation. To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension. Randomized controlled trial. A total of 975 [corrected] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication. Four academic health centers. The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention. Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months). The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups. Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

CD003656

Intensive interventions, unsuited to primary care or population prevention programmes, provide only minimal reductions in blood pressure during long-term trials. Further evaluations to assess effects on morbidity and mortality outcomes are needed for populations as a whole and for patients with elevated blood pressure. A low sodium diet may help in maintenance of lower blood pressure following withdrawal of antihypertensives. If this is confirmed, with no increase in cardiovascular events, then targeting of comprehensive dietary and behavioural programmes in patients with elevated blood pressure requiring drug treatment would be justified.

Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group.

To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period. We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided. From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82). In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Chelation therapy in beta-thalassemia major. I. Intravenous and subcutaneous deferoxamine.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Comparative efficacy of desferrioxamine, deferiprone and in combination on iron chelation in thalassemic children.

Ascertainment of an appropriate strategy of iron chelation for multi-transfused thalassemic children in developing countries. Prospective study from May 2000 to April 2001. Urban tertiary care center. Thirty thalassemic children having received more than 20 blood transfusions and a serum ferritin greater than 1500 ng/ml were enrolled and randomized into three groups. Group I received desferrioxamine (DFX) at a dose of 40 mg/kg subcutaneously, 5 days/week. Children in group II received oral deferiprone (L1) at a dose of 75 mg/kg/day daily and group III received a combination of daily L1 at a dose of 75 mg/kg/day and DFX at a dose of 40 mg/kg/day two times per week. The assessment of chelation was done by 24-hr urinary iron excretion (UIE) and measurement of serum ferritin levels at start and after 6 months of follow up. Statistical difference of serum ferritin levels between the three groups was assessed by applying analysis of variance. Analysis of covariance was applied to find out the urinary iron excretion keeping serum ferritin values same in each groups. Ferritin levels after 6 months of intervention were maximally decreased in group I. There was a significant difference between groups I and II however, no difference was noted between groups I and group III. There was no statistically significant difference in mean urinary iron excretion by keeping the initial serum ferritin levels equal though it was found to be more in group III as compared to other groups. DFX is the most effective chelating drug in iron overloaded multi-transfused thalassemic patients. In view of cost and unacceptability of daily DFX injections, combination therapy is an effective method of chelation thus increasing the compliance and cost effectiveness. Deferiprone (L1) alone is not an effective mode of chelation when used for a short period.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial.

Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willing to undergo liver biopsy before and after treatment. The mean serum ferritin reduction was 222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine group (P = 0.81). No difference in the reduction of liver and heart iron content was found by magnetic resonance between the two groups. Thirty-six patients accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511 microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in variation of the Ishak fibrosis stage was observed between the two groups. Treatment was discontinued because of reversible side effects in 5 patients in the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none in the deferoxamine group. These findings suggest that deferiprone may be as effective as deferoxamine in the treatment of thalassemia major with few mild and reversible side effects.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients.

The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was compared with that of subcutaneous desferrioxamine in 26 patients with transfusional iron overload. Immediately after red-cell transfusion, 20 patients were randomised to receive either desferrioxamine (50 mg/kg daily as a 12 h subcutaneous infusion), or L1 (50 mg/kg daily by mouth). Patients were evaluated during treatment with the other drug after transfusion the next month. Mean (SD) daily urinary iron excretion was lower during L1 than during desferrioxamine (12.3 [6.7] vs 18.2 [15.3] mg/day). In 5 patients the dose of L1 was raised from 50 to 75 mg/kg daily; mean urinary iron excretion rose from 13.8 (7.0) mg/day to 26.7 (17.8) mg/day, comparable with that during desferrioxamine (24.9 [24.3] mg/day). Faecal iron excretion rose slightly over baseline in 6 patients studied during L1 administration (from 8.5 [0.9] mg/day to 12.2 [0.9] mg/day). Pharmacokinetic studies showed an elimination half-life for L1 of 117-237 min. Studies in dogs and in volunteers showed no absorption of the L1-iron complex, excluding a contribution of absorption of intraluminal complexes of L1 and food iron to urinary iron excretion. Further animal toxicity testing is needed before L1 can be studied in a broader group of patients.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Evaluation of a new method of administration of the iron chelating agent deferoxamine.

We compared the effectiveness of deferoxamine administered by twice-daily subcutaneous injections with conventional administration by prolonged subcutaneous infusion in 20 patients with thalassemia. Urinary iron excretion was comparable with the two methods but decreased significantly when the total daily dose was administered as a single injection. Local reactions were similar with infusion and injection. Subcutaneous injections of deferoxamine may be considered as an alternative to conventional infusions.

CD004450

We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients.

Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

A randomized prospective study on the effect of short and long buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response.

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I--long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II--short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P less than 0.01). Cancellation rate was significantly lower in Group I than in Group II (P less than 0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos transferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Ovarian response and outcome of in-vitro fertilization in patients treated with gonadotrophin-releasing hormone analogues in different phases of the menstrual cycle.

Gonadotrophin-releasing hormone analogues (GnRH-a) are currently used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). The present study evaluates follicular recruitment and outcome of IVF in patients treated with GnRH-a, starting in different phases of the menstrual cycle. Ovarian quiescence was achieved by s.c. injection of a GnRH-a (600 micrograms/day). Three groups of patients were randomly established. Patients in group 1 (n = 14) started GnRH-a treatment 4-7 days after ovulation. Women in group 2 (n = 15) started GnRH-a 8-10 days after ovulation. Patients in group 3 (n = 15) began the analogue 1-3 days after the onset of menses. Multiple follicular development was achieved by a combination of pure follicle-stimulating hormone and human menopausal gonadotrophin. Oocyte collection was performed 35 h after administration of human chorionic gonadotrophin. Luteolysis was successfully induced in 15% of cases in group 1 and 40% in group 2. Ovarian arrest was achieved in a significantly (P less than 0.01) shorter period of time in group 3 in comparison to groups 1 and 2. There was no difference between groups in the dose of gonadotrophins necessary to reach an optimal response. Patients in group 1 showed a significant decrease (P less than 0.05) in the number and size of follicles developed in comparison to groups 2 and 3. Fertilization and cleavage rates were similar in all three groups. The pregnancy rate was 40% in group 3, while it decreased to 14.3 and 13.3% in groups 1 and 2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Prospective study of short and long regimens of gonadotropin-releasing hormone agonist in in vitro fertilization program.

To assess the usefulness of a short regimen in ovulation induction in an in vitro fertilization (IVF) program. A prospective randomized trial was set up to compare long and short regimens of gonadotropin-releasing hormone agonist administration for ovulation induction in IVF. Aberdeen Assisted Reproduction Unit. Eighty-seven patients undergoing IVF were randomized between the two protocols. Stimulation regimen was the only variable being tested. Stimulation response and occurrence of luteinizing hormone (LH) surges. There was no difference in the stimulation requirements, response to stimulation, number of follicles aspirated, or the number of oocytes obtained. The fertilization rates, number of embryos transferred, and pregnancy rates were also similar in both groups. Like the long regimen, it prevents the occurrence of a premature LH surge. The short regimen is a useful and cheaper alternative in ovarian stimulation of patients undergoing IVF.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Comparison between flare up and down regulation effects of luteinizing hormone-releasing hormone agonists in an in vitro fertilization program.

Luteinizing hormone-releasing hormone (LH-RH) agonists are being increasingly used in ovulation stimulation protocols in IVF programs. The results of two methods of utilization of LH-RH agonists are compared. In the long protocol, gonadotropin stimulation was commenced only after a preliminary period of pituitary desensitization with LH-RH agonist. In the short protocol, exogenous gonadotropins were administered shortly after the start of LH-RH agonist therapy, benefiting from the gonadotropin flare up effect. One hundred eighty-six patients were equally divided between the two treatments. There was no difference in the ovarian response on the day of human chorionic gonadotropin (hCG) or the number of mature oocytes recovered. The cleavage rate of mature oocytes was higher in the short protocol (70% versus 56% P less than 0.01). The ongoing pregnancy rate per treatment cycle was similar in both groups (18% in the long protocol and 16% in the short protocol). Analysis of the luteal phases revealed a trend for higher progesterone values in the long protocol although this was only significant on the 2nd day following oocyte retrieval. As the clinical results were similar, other factors should be taken into account when deciding therapy. These include patient convenience, cost, and side effects. Other schedules of ovulation stimulation with LH-RH agonists are discussed.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Effect of halving the daily dose of triptorelin at the start of ovarian stimulation on hormone serum levels and the outcome of in vitro fertilization.

Halving the standard daily dose of triptorelin at the start of ovarian stimulation in down-regulated women stimulated with recombinant FSH is enough for pituitary suppression and was associated with higher LH serum concentrations in the follicular phase. However, this did not translate into higher serum concentrations of androstenedione and E2 and had no significant effect on ovarian response and the outcome of IVF/intracytoplasmic sperm injection.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Midluteal buserelin is superior to early follicular phase buserelin in combined gonadotropin-releasing hormone analog and gonadotropin stimulation in in vitro fertilization.

To establish whether time to down-regulation and pregnancy and live birth rates were different when buserelin acetate was started in the midluteal phase or early follicular phase in IVF-ET patients. Prospective, controlled, randomized, parallel-group multicenter clinical study. Women attending seven infertility clinics. One hundred twenty-four women with tubal or unexplained infertility with normal menstruation and fertile partners. Intranasal buserelin acetate started in the midluteal or early follicular phase combined with standard hMG and hCG stimulation after achievement of down-regulation. Established IVF-ET methods. Duration of down-regulation; clinical pregnancy and live birth rates. Kaplan-Meier estimations of the duration of down-regulation were 15.5 days when buserelin acetate was started in the early follicular phase (127 cycles) and 14.6 days when it was started in the midluteal phase (96 cycles). This difference was statistically significant. The pregnancy rates per first treatment cycle, treatment cycle, oocyte retrieval, and ET were significantly higher when buserelin acetate was started in the midluteal phase. The live birth rates were also higher, but only significantly so for the rate per first treatment cycle. Clinical pregnancy and live birth rates are better when buserelin acetate is started in the midluteal phase rather than the early follicle phase before hMG and hCG stimulation in preparation for IVF-ET.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Effect of reduced dose of triptorelin at the start of ovarian stimulation on the outcome of IVF: a randomized study.

Partial pituitary desensitization using gonadotrophin-releasing hormone (GnRH) agonists may be sufficient in women undergoing controlled ovarian hyperstimulation for assisted reproduction. However, the minimal effective agonist dose remains to be determined. The aim of the study was to investigate the effect of a reduced daily dose of triptorelin, administered at the start of ovarian stimulation, on the results of IVF and intracytoplasmic sperm injection. A total of 132 patients was randomized in two groups. Pituitary desensitization was obtained in group 1 (66 patients) with a single 3.75 mg injection (i.m.) of triptorelin. In group 2, 66 patients received 100 microg triptorelin daily, which was then reduced to 50 microg at the start of follicle-stimulating hormone (FSH) stimulation. No significant differences were found in terms of pregnancy rate per transfer (38% in group 1 versus 34.9% in group 2), implantation rate (20.2 versus 18%) and abortion rate (8.3 versus 9.1%). The number of FSH ampoules used, as well as the number of days stimulation required, was significantly reduced in group 2 (41 +/- 26 versus 46.6 +/- 25.3, P < 0.03 and 11 +/- 1.3 versus 11.8 +/- 1.5, P < 0.002 respectively). No significant differences were seen in oestradiol concentrations and in follicle number, in the quantity of oocytes collected and fertilized, or in the number of embryos obtained or transferred. A reduced dose of triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation. The possibility of a shorter treatment protocol requiring lower amounts of gonadotrophins should be considered in view of its economic advantage.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

[Systematic inhibition of the luteinizing hormone with a gonadoliberin analog, triptorelin, during ovarian stimulation for fertilization in vitro. Choice of protocol].

The quality of ovarian stimulation for in vitro fertilization with or without an LH-RH analogue was investigated in a randomized trial involving 30 women divided into 3 groups. Group I women were treated with the conventional clomiphene citrate-human menopausal gonadotropin combination without LH-RH analogue. Group II women (long regimen) received a slow-release preparation of triptorelin (DTRp6-LH-RH), an LH-RH analogue, and human menopausal gonadotropin. Group II women (short regimen) were given triptorelin with human menopausal gonadotropin. Inhibition of the endogenous luteinizing hormone using triptorelin improved the results of in vitro fertilization in group II and group III women, but the short regimen was distinctly less compelling and less expensive than the long regimen.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial.

Recent evidence suggests that early cessation of gonadotrophin releasing hormone analogue (GnRHa) administration may offer some benefit to low responder patients undergoing IVF. A prospective, randomized controlled trial was designed to evaluate whether early cessation of GnRHa in an ovarian stimulation regimen is more beneficial than just increasing the doses of gonadotrophins. Seventy low responder patients (less than three mature follicles in a previous cycle) with normal basal follicle stimulating hormone concentrations and a previous cancelled IVF cycle were randomly allocated into two protocols: (i) non-stop protocol: long GnRHa suppression with high doses of gonadotrophins, and (ii) stop protocol, in which GnRHa administration is stopped with the onset of menses, while gonadotrophin doses remained similar to the non-stop protocol. A significantly higher number of mature oocytes were obtained in the study group (stop protocol) compared to the control group (non-stop protocol) (8.7 +/- 0.9 versus 6.2 +/- 0.7, P: = 0. 027). The stop protocol reduced the number of ampoules of gonadotrophins required (56.6 +/- 2.7 versus 68.0 +/- 3.5, P: = 0. 013). Both protocols resulted in a similar cancellation rate (2.7 versus 5.8%) (with no cycles cancelled due to ovulation), pregnancy rate (14.3 versus 18.7%), and implantation rate (12.1 versus 8.8%). The early cessation of GnRHa combined with high doses of gonadotrophins permitted the retrieval of a significantly higher number of oocytes.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. Prospective randomized study. Ninety-one patients having their first attempt at IVF. Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study.

To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage. Prospective randomized study. Three hundred eight patients having their first ever IVF attempt. Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n = 81); clomiphene citrate and hMG (group B, n = 77); a 3-day ultrashort course of GnRH-a and hMG (group C, n = 74); or pituitary desensitization with GnRH-a followed by hMG (group D, n = 76). The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer. The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization.

To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. A prospective, randomized controlled trial. Hospital-based IVF Unit. Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. Ovarian stimulation patterns and IVF outcome. A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Hormonal changes induced by short-term administration of gonadotropin-releasing hormone agonist during ovarian hyperstimulation for in vitro fertilization and their consequences for embryo development.

Several regimens have been developed to administer gonadotropin-releasing hormone agonists in association with human menopausal gonadotropins (hMG) during follicular growth stimulation for in vitro fertilization. The aim of this study was to characterize hormonal changes induced by short-term administration of agonist, and to evaluate a putative impact of the flare-up effect on follicular recruitment and subsequent IVF. Eighteen highly selected patients were randomely divided in two groups. Nine patients received a short-term administration of Buserelin (Hoechst, AG, Franfurt/Main, FRG) (day 1). They were compared with 9 patients who were exposed to a long-term protocol (day 21), and 13 control patients. Agonist-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increase, in early follicular phase, stimulated follicular growth, shortened follicular phase, and induced a transient rise in progesterone. This was followed by a phase of reduced LH secretion associated with a significant modification of LH immunoreactivity. The short-term regimen did not improve the follicular recruitment, and appeared to reduce the oocytes fertilization rate and embryo quality when compared with prolonged administration of peptide.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Comparison of ovarian stimulation regimens for in vitro fertilization (IVE) with and without a gonadotropin-releasing hormone (GnRH) agonist: results of a randomized study.

In order to diminish the cancellation rate due to a premature endogeneous LH surge and/or to a poor ovarian response and thus increasing the pregnancy rate, a GnRH agonist (Buserelin) was applied in patients starting their first ovarian stimulation with gonadotropins for IVF. All patients suffered from tubal infertility and were not older than 40 years. Each woman was allocated randomly to one of three groups: the conventional treatment with hMG alone (group I), patients from group II started the hMG treatment shortly after the LH rise caused by the GnRH agonist and patients in group III commenced the hMG treatment when an hypogonadotropic state was achieved after a long treatment of Buserelin. All male partners had a normal spermiogram. A reduction of poor responders to the superovulation is seen in the short-term group (6%), compared with the other two groups (14%). In some cases from group III ovarian cyst formation led to the cancellation of the treatment. The long-term group differs significantly from the other two in the duration of the gonadotropin stimulation and the number of ampoules hMG used. A severe ovarian overstimulation syndrome was not observed. There is no difference in the number of retrieved oocytes and the fertilization rate among the three groups. The pregnancy rate per cycle or per patient in the group with a short-term GnRH-agonist regimen is significantly higher compared to that of the group using the conventional hMG treatment.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation.

To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). A prospective randomized trial. The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France. One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period. Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. Response to COH, pregnancy rate (PR), tolerance. In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization.

A randomized prospective study was undertaken to compare low and standard luteinizing hormone-releasing hormone agonist (LHRHa) dosage used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). A total of 42 ovulatory patients with mechanical infertility were administered 0.5 mg/day LHRHa (Decapeptyl) from day 21 of their cycles for 14 days. Following down-regulation, patients were randomly allocated to continue with the same dose of LHRHa (22 patients, group A) or to receive a lower dose of 0.1 mg/day LHRHa (20 patients, group B) during folliculogenesis. Luteal phase was supported by daily i.m. progesterone (50 mg) injections and human chorionic gonadotrophin (HCG; 1500 IU) every 4 days. Ovarian response, human menopausal gonadotrophin (HMG) dosage used for induction of ovulation, evidence of premature luteinization, and clinical and laboratory IVF outcome, were compared between groups A and B. The two groups were comparable in respect of: age (32.6 +/- 0.7 and 33.0 +/- 0.9 years), HMG dosage (33.0 +/- 1.6 and 36.0 +/- 2.5 ampoules), day of HCG (11.2 +/- 0.3 and 12.2 +/- 0.4), oocytes/patient (13.3 +/- 1.0 and 12.9 +/- 1.3), fertilization rate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryo transfer (32 and 35%) and implantation rate (10.8 and 10.5%), for groups A and B respectively. There was no evidence of premature luteinization or luteolysis in either group. It was concluded that lowering the dose of LHRHa to 0.1 mg/day during folliculogenesis had no adverse effect on ovarian response or clinical results. However, it had no advantage in reducing the HMG dose used for ovulation induction.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Is long-protocol gonadotropin releasing hormone agonist administration superior to the short protocol in ovarian stimulation for in vitro fertilization?

To compare the long and short protocols of gonadotropin releasing hormone agonist (GnRH-a) administration for ovarian stimulation. University hospital. 90 patients on their first attempt at in vitro fertilization and embryo transfer (IVF-ET). The results of two stimulation protocols were compared with respect to number of follicles greater than 17 mm, peak serum estradiol level, number of oocytes retrieved and fertilized, fertilization rate per oocyte, number of embryos transferred, and pregnancy rate per initiated cycle. The number of follicles greater than 17 mm and the peak estradiol level were significantly (P < .05) higher in the long protocol than those in the short protocol. The number of oocytes retrieved and fertilized, the number of embryos transferred, and the pregnancy rate per initiated cycle were also significantly (P < .001) higher in the long protocol than those in the short protocol. The fertilization rates per oocyte retrieved did not differ significantly between groups. The long protocol of gonadotropin releasing hormone agonist administration for ovarian stimulation in IVF-ET may be the preferred method when GnRH-a is used.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

A randomized prospective study of early follicular or midluteal initiation of long protocol gonadotropin-releasing hormone in an in vitro fertilization program.

To determine the optimum menstrual cycle time to initiate a long-protocol gonadotropin-releasing hormone agonist (GnRH-a) down-regulation regimen before hMG stimulation before IVF. Randomized, prospective, single, first cycle study. University teaching hospital. Eighty-six infertile couples undergoing IVF-ET attempt under rules for Ireland. Gonadotropin-releasing hormone agonist administered intranasally from day 1 or 21 of menstrual cycle. Human menopausal gonadotropin commenced when pituitary down-regulation was confirmed. Ovarian response, cancellation, fertilization, and pregnancy rates. No significant differences found between day 1 and day 21 initiation. But starting on day 1 is more easily recognizable by patients and avoids the possibility of administering GnRH-a in the presence of an unsuspected pregnancy. Both follicular and luteal phase initiation of GnRH-a long-protocol down-regulation are equally efficacious. In our clinical context, patients and management favor commencing on day 1.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Consequences on gonadotrophin secretion of an early discontinuation of gonadotrophin-releasing hormone agonist administration in short-term protocol for in-vitro fertilization.

Administration of gonadotrophin-releasing hormone (GnRHa) agonists, used in IVF short-term protocols to initiate follicular recruitment, may be restricted to the early follicular phase without any further risk of LH surge. However, consequences of an early discontinuation upon residual endogenous gonadotrophin secretion are still unknown. Here, the effects of early cessation of GnRH agonist upon gonadotrophin secretion and ovarian parameters of IVF cycles were investigated. A total of 230 normo-ovulatory women were prospectively allocated to one of the two regimens: decapeptyl-GnRH (100 microgram) was daily injected either from day 1 to the triggering of ovulation (group 1) or for the first 7 days (group 2). Exogenous gonadotrophins (150 IU) were administered on day 4 and 5 with a subsequent adjustment. Detections of free alpha subunit and dimeric LH were performed by highly specific 'two site' monoclonal immunoradiometric assays. The results show that early discontinuation of GnRH agonist administration was associated with a sharp decrease in both plasma free alpha subunit and dimeric LH concentrations while plasma oestradiol response to exogenous gonadotrophins was reduced. Other ovarian parameters and pregnancy rate were unchanged. These data indicate that endogenous LH secretion is maintained by a daily administration of GnRH agonist and may contribute to the final follicular maturation.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embryo transfer.

To compare two stimulation protocols designed for low responders undergoing IVF. Randomized, prospective study. University hospital IVF unit. Sixty low responders who were recruited on the basis of results in previous cycles. Modified flare protocol in which a high dose of GnRH agonist was administered for the first 4 days, followed by a standard agonist dose, or a modified long protocol in which a standard agonist dose was used until pituitary down-regulation, after which the agonist dose was halved during stimulation. Number of oocytes retrieved. Twenty-nine cycles were performed with the modified flare protocol and 31 were performed with the modified long protocol. Significantly more oocytes were obtained with the modified long protocol than the modified flare protocol (4.42 +/- 2.6 vs. 3.07 +/- 2.15). The number and quality of embryos available for transfer was similar in both groups. One clinical pregnancy (3.4%) was achieved with the modified flare protocol, and 7 pregnancies (22.5%) were achieved using the modified long protocol. These preliminary results substantiate the poor prognosis and outcome for low responders undergoing IVF. A modified long "mini-dose" protocol appears to be superior to a modified mega-dose flare protocol in terms of oocyte yield and cycle outcome.

CD006919

The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

The comparison of early follicular and midluteal administration of long-acting gonadotropin-releasing hormone agonist.

Long-acting GnRH-a (D-Trp6 microcapsules, 3.2 mg) was intramuscularly injected, either in early follicular phase (group A) or midluteal phase (group B). Two hundred sixteen cycles were randomly allocated. Ovarian suppression was significantly more prompt in group B. Follicle cysts were diagnosed in 19% and 16% of groups A and B, respectively; their appearance and regression were significantly more rapid in group B cycles. More ampules of human menopausal gonadotropin were needed in group B. The number of oocytes retrieved was not significantly different between the groups. However, in group A more mature oocytes and more embryos with good morphology were achieved in the patients. Cancellation rate was 2.8% in groups A and B. Pregnancy rate and outcome were similar in both groups.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder.

This study examines the therapeutic effect of fluoxetine, a selective serotonin reuptake inhibitor, added to dialectical behavior therapy (DBT), an empirically supported psychosocial therapy, for the treatment of borderline personality disorder. This is a 12-week, randomized, double-blind, placebo-controlled study of patients with borderline personality disorder (identified using the Structured Clinical Interview for DSM-IV Axis II Disorders). All subjects received individual and group DBT. Of the 20 subjects that completed treatment, 9 were randomly assigned to receive up to 40 mg/day of fluoxetine and 11 were randomly assigned to the placebo condition. Subjects were evaluated at baseline and at week 10 or 11 on self-report measures of depression, anxiety, anger expression, dissociation, and global functioning. The study was conducted between January 1998 and February 2000. Time-by-group interaction effects revealed no significant group differences in scores from pre-treatment to posttreatment on any measure. However, within the DBT/placebo group, there were significant pretreatment/posttreatment differences in the direction of improvement on all measures. No significant pre-treatment/posttreatment differences were found within the DBT/fluoxetine condition. The data suggest that adding fluoxetine to an efficacious psychosocial treatment does not provide any additional benefits. Further studies with larger sample sizes are warranted.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial.

Trials have demonstrated benefits of long-chain omega-3 essential fatty acid (n-3 EFA) supplementation in a variety of psychiatric disorders. To assess the efficacy of n-3 EFAs in improving psychological well-being in patients with recurrent self-harm. Patients (n=49) presenting after an act of repeated self-harm were randomised to receive 1.2 g eicosapentaenoic acid plus 0.9 g decosahexaenoic acid (n=22) or placebo (n=27) for 12 weeks in addition to standard psychiatric care. Six psychological domains were measured at baseline and end point. At 12 weeks, the n-3 EFA group had significantly greater improvements in scores for depression, suicidality and daily stresses. Scores for impulsivity, aggression and hostility did not differ. Supplementation achieved substantial reductions in surrogate markers of suicidal behaviour and improvements in well-being. Larger studies are warranted to determine if insufficient dietary intake of n-3 EFAs is a reversible risk factor for self-harm.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Topiramate treatment for women with borderline personality disorder: a double-blind, placebo-controlled study.

Borderline personality disorder is a common and severe psychiatric illness. The goal of this study was to determine whether topiramate can influence patients' borderline psychopathology, health-related quality of life, and interpersonal problems. Women meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Structured Clinical Interview II criteria for borderline personality disorder were randomly assigned in a 1:1 ratio to topiramate titrated from 25 to 200 mg/d (n = 28) or placebo (n = 28) for 10 weeks. Primary outcome measures were changes on the Symptom-Checklist, on the SF-36 Health Survey, and on the Inventory of Interpersonal Problems. Body weight and additional side effects were assessed weekly. According to the intent-to-treat principle, significant changes (all P < 0.001) on the somatization, interpersonal sensitivity, anxiety, hostility, phobic anxiety, and Global Severity Index scales of the Symptom Checklist were observed in the topiramate-treated subjects after 10 weeks (no significant changes on the obsessive-compulsive, depression, paranoid ideation, and psychoticism scales). In the SF-36 Health Survey, significant differences were observed on all 8 scales (all P < 0.01 or P < 0.001). In the Inventory of Interpersonal Problems, significant differences (all P < 0.001) were found in the scales for overly autocratic, overly competitive, overly introverted, and overly expressive (no significant differences in the scales for overly cold, overly subassertive/subservient, overly exploitable/compliant, and overly nurturant/friendly). Weight loss was additionally observed (p < 0.001). Topiramate appears to be a safe and effective agent in the treatment in women with borderline personality disorder. Additional weight loss can be expected.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Response of borderline patients to loxapine and chlorpromazine.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder.

The objective of this study was to evaluate the effectiveness of lamotrigine in reducing affective instability in borderline personality disorder (BPD). We conducted a 12-week, double-blind, placebo-controlled study of 28 patients who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for BPD. Patients could not meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for bipolar disorder. Patients could be taking one antidepressant during the study. Patients were randomly assigned to treatment with flexible-dose lamotrigine or placebo in a 1 : 1 manner. The primary outcome measures were: (i) the Affective Lability Scale total score; and (ii) the Affective Instability Item of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The study randomized 15 patients to receive lamotrigine and 13 patients to receive placebo. Patients in the lamotrigine group had significantly greater reductions in the total Affective Lability Scale scores (P<0.05) and significantly greater reductions in scores on the affective instability item of the ZAN-BPD (P<0.05). A secondary finding was that patients in the lamotrigine group had significantly greater reductions in scores on the ZAN-BPD impulsivity item (P = 0.001). Results from the study suggest that lamotrigine is an effective treatment for affective instability and for the general impulsivity characteristic of BPD.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Amitriptyline versus haloperidol in borderlines: final outcomes and predictors of response.

The authors report the final results of a 4-year study of amitriptyline and haloperidol in 90 symptomatic borderline inpatients. Medication trials were double-blind and placebo controlled and lasted 5 weeks. Haloperidol (4-16 mg/day) produced significant improvement over placebo in global functioning, depression, hostility, schizotypal symptoms, and impulsive behavior. Significant effects of amitriptyline (100-175 mg/day) were generally limited to measures of depression. Factor analysis identified three symptom change patterns: a global depression, hostile depression, and schizotypal symptom pattern. Medication effects favoring haloperidol were most prominent for hostile depression. Variables predicting favorable response to haloperidol included severity of schizotypal symptoms, hostility, and suspiciousness. Schizotypal symptoms and paranoia predicted poor outcome on both depression patterns with amitriptyline. Placebo effects were most prominent on acute state symptoms, with severe character traits predicting poor response.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: a double-blind placebo-controlled pilot study.

The intent of this study was to compare the efficacy and safety of divalproex sodium and placebo in the treatment of women with borderline personality disorder and comorbid bipolar II disorder. We conducted a placebo-controlled double-blind study of divalproex sodium in 30 female subjects aged 18 to 40 years who met Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder and DSM-IV criteria for bipolar II disorder. Subjects were randomly assigned to divalproex sodium or placebo in a 2:1 manner. Treatment duration was 6 months. Primary outcome measures were changes on the interpersonal sensitivity, anger/hostility, and depression scales of the Symptom Checklist 90 (SCL-90) as well as the total score of the modified Overt Aggression Scale (MOAS). Twenty subjects were randomly assigned to divalproex sodium; 10 subjects to placebo. Using a last-observation-carried-forward paradigm and controlling for baseline severity, divalproex sodium proved to be superior to placebo in diminishing interpersonal sensitivity and anger/hostility as measured by the SCL-90 as well as overall aggression as measured by the MOAS. Adverse effects were infrequent. The results of this study suggest that divalproex sodium may be a safe and effective agent in the treatment of women with criteria-defined borderline personality disorder and comorbid bipolar II disorder, significantly decreasing their irritability and anger, the tempestuousness of their relationships, and their impulsive aggressiveness.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.

The aim of this study was to determine the efficacy and safety of dialectical behavior therapy plus olanzapine compared with dialectical behavior therapy plus placebo in patients with borderline personality disorder. Sixty patients with borderline personality disorder were included in a 12-week, double-blind, placebo-controlled study. All patients received dialectical behavior therapy and were randomly assigned to receive either olanzapine or placebo following a 1-month baseline period. Seventy percent of the patients completed the 4-month trial. Combined treatment showed an overall improvement in most symptoms studied in both groups. Olanzapine was associated with a statistically significant improvement over placebo in depression, anxiety, and impulsivity/aggressive behavior. The mean dose of olanzapine was 8.83 mg/day. A combined psychotherapeutic plus pharmacological approach appears to lower dropout rates and constitutes an effective treatment for borderline personality disorder.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Treatment of aggression with topiramate in male borderline patients: a double-blind, placebo-controlled study.

Borderline personality disorder (BPD) is a complex mental disease associated with severe serious functional impairment, affective instability, and impulsive aggression. The aim of this study was to compare the efficacy of topiramate versus placebo in the treatment of aggression in men with borderline personality disorder. We conducted an 8-week, double-blind, placebo-controlled study of topiramate in 42 male subjects (42 of 44) meeting DSM-IV criteria for BPD. The Structured Clinical Interview (SCID I and II) was carried out. The subjects were randomly assigned to topiramate (n = 22) or placebo (n = 20). Significant changes on four STAXI scales (State Anger, p < .01; Trait Anger, p < .05; Anger Out, p < .01; Anger Control, p < .01) were observed in the subjects treated with topiramate. A nonsignificant difference was found on the Anger In scale (p = .86). Additional significant weight loss was observed (difference in weight loss between the both groups was 5.0 kg, p < .01, 95% confidence interval = [-6.5 to 3.4]). All subjects tolerated topiramate relatively well. Topiramate appears to be an effective agent in the treatment of anger in men with BPD. Mild weight loss can be expected.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Ziprasidone in the treatment of borderline personality disorder: a double-blind, placebo-controlled, randomized study.

The aim of this double-blind, placebo-controlled study was to evaluate the efficacy and tolerability of ziprasidone in the treatment of adult patients with borderline personality disorder. Sixty DSM-IV borderline personality disorder patients were included from March 2004 to April 2006 in a 12-week, single-center, double-blind, placebo-controlled study. The subjects were randomly assigned to ziprasidone or placebo in a 1:1 ratio following a 2-week baseline period. The Clinical Global Impressions scale for use in borderline personality disorder patients (CGI-BPD) was the primary outcome measure, and other scales and self-reports related to affect, behavior, psychosis, general psychopathology domains, and clinical safety were included. Analysis of variance indicated no statistically significant differences between ziprasidone and placebo in the CGI-BPD. Nor were significant differences observed between groups in depressive, anxiety, psychotic, or impulsive symptoms. The mean daily dose of ziprasidone was 84.1 mg/day (SD = 54.8; range, 40-200). The drug was seen to be safe, and no serious adverse effects were observed. This trial failed to show a significant effect of ziprasidone in patients with borderline personality disorder. clinicaltrials.gov Identifier: NCT00635921.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Olanzapine versus placebo in the treatment of borderline personality disorder.

Atypical antipsychotics are increasingly used in clinical practice in the management of borderline personality disorder (BPD), and a small but growing body of literature supports their efficacy. Here, we report the results of a double-blind, placebo-controlled study of olanzapine as a treatment for BPD. Forty BPD patients (25 female, 15 male) were randomly assigned in equal numbers to olanzapine and placebo. Diagnoses were made using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Mini-International Neuropsychiatric Interview. Patients with schizophrenia, bipolar disorder, or current major depression were excluded. Olanzapine dosage was flexible, and the dose range was 2.5 to 20 mg/day, with most patients receiving 5 to 10 mg/day. No concomitant psychotropic medications were allowed. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks. The primary outcome was change in the total score for the 9 BPD criteria on a 1-to-7 Likert scale, the Clinical Global Impressions scale modified for borderline personality disorder (CGI-BPD), using an analysis of covariance model including baseline score as covariate. Data were collected from July 2000 to April 2002. Olanzapine was found to be significantly (p <.05) superior to placebo on the CGI-BPD at endpoint, with separation occurring as early as 4 weeks. Similar results were found for the single-item Clinical Global Impressions scale. Weight gain was significantly (p =.027) greater in the olanzapine group. This study supports the efficacy of olanzapine for symptoms of BPD in a mixed sample of women and men. Further studies with olanzapine and other atypical antipsychotics are needed.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Efficacy of phenelzine and haloperidol in borderline personality disorder.

To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. Randomized, double-blind, placebo-controlled trial. Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study.

The purpose of this study was to compare the efficacy of ethyl-eicosapentaenoic acid (E-EPA) and placebo in the treatment of female subjects with borderline personality disorder. The authors conducted an 8-week, placebo-controlled, double-blind study of E-EPA in 30 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder. Twenty subjects were randomly assigned to 1 g of E-EPA; 10 subjects were given placebo. Ninety percent of those in both groups completed all 8 weeks of the trial. Analyses that used random-effects regression modeling and controlled for baseline severity showed E-EPA to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms. The results of this study suggest that E-EPA may be a safe and effective form of monotherapy for women with moderately severe borderline personality disorder.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study.

The intent of this study was to compare the efficacy and safety of olanzapine versus placebo in the treatment of women meeting criteria for borderline personality disorder (BPD). We conducted a double-blind, placebo-controlled study of olanzapine in 28 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for BPD. The subjects were randomly assigned to olanzapine or placebo in a 2:1 manner. Treatment duration was 6 months. Primary outcome measures were self-reported changes on anxiety, depression, paranoia, anger/hostility, and interpersonal sensitivity scales of the Symptom Checklist-90. Nineteen subjects were randomly assigned to olanzapine; 9. to placebo. When random effects regression modeling of panel data was used, controlling for baseline level of severity, olanzapine was associated with a significantly (p < .05) greater rate of improvement over time than placebo in all of the symptom areas studied except depression. Weight gain was modest in the olanzapine-treated group but was significantly higher than in those treated with placebo (p < .02). In addition, no serious movement disorders were noted. Olanzapine appears to be a safe and effective agent in the treatment of women with criteria-defined BPD, significantly affecting all 4 core areas of borderline psychopathology (i.e., affect, cognition, impulsivity, and interpersonal relationships).

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

A preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapine-fluoxetine combination in women with borderline personality disorder.

The intent of this study was to compare the efficacy and safety of fluoxetine, olanzapine, or the olanzapine-fluoxetine combination (OFC) in the treatment of women meeting criteria for borderline personality disorder (without concurrent major depressive disorder). We conducted a randomized double-blind study of these agents in female subjects meeting Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-IV criteria for borderline personality disorder. Treatment duration was 8 weeks. Outcome measures were clinician-rated scales measuring depression (the Montgomery-Asberg Depression Rating Scale) and impulsive aggression (the Modified Overt Aggression Scale). Data were collected from August 2001 through March 2003. Fourteen subjects were randomized to fluoxetine; 16, to olanzapine; and 15, to OFC. Forty-two of these subjects (93.3%) completed all 8 weeks of the trial. Using random-effects regression modeling of panel data of change-from-baseline scores and controlling for time, olanzapine monotherapy and OFC were associated with a significantly greater rate of improvement over time than fluoxetine on both outcome measures. However, it should be noted that fluoxetine treatment led to a substantial reduction in impulsive aggression and severity of depression. Weight gain was relatively modest in all 3 groups but significantly greater in the olanzapine-treated group than in the groups treated with fluoxetine alone or OFC. All 3 compounds studied appear to be safe and effective agents in the treatment of women with borderline personality disorder, significantly ameliorating the chronic dysphoria and impulsive aggression common among borderline patients. However, olanzapine monotherapy and OFC seem to be superior to fluoxetine monotherapy in treating both of these dimensions of borderline psychopathology.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder.

Clinical data and uncontrolled observations have suggested that fluoxetine is helpful in some patients with borderline personality disorder. This article describes the results of a 13-week double-blind study of volunteer subjects with mild to moderately severe borderline personality disorder. Thirteen fluoxetine recipients and nine placebo recipients received treatment. Pretreatment and posttreatment measures were obtained for global mood and functioning, anger, and depression. The most striking finding from this study was a clinically and statistically significant decrease in anger among the fluoxetine recipients. This decrease was independent of changes in depression. These data support previous observations that fluoxetine may reduce anger in patients with borderline personality disorder. The number of subjects in this study was small, the placebo responsiveness was high, and the clinical characteristics of the patients were in the mild to moderate range of severity. The data cannot be extrapolated to more severely ill borderline patients, but further study of fluoxetine and other selective serotonin reuptake inhibitors is indicated in this population.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Borderline and schizotypal personality disorders treated with low-dose thiothixene vs placebo.

Fifty outpatients with borderline and/or schizotypal personality disorder were randomly allocated to thiothixene (Navane) or placebo treatment that was continued for 12 weeks. The mean daily dosage of thiothixene hydrochloride in the final week of the study was 8.7 mg, a lower dosage than is used in outpatient schizophrenics. Significant drug-placebo differences were found, regardless of diagnosis, on "illusions," "ideas of reference," "psychoticism," "obsessive-compulsive symptoms," and "phobic anxiety," but not on "depression." Thiothixene seems to have more than an antipsychotic effect. Since response to treatment studies are a means for reformulating diagnostic concepts, we suggest a subdiagnosis defined by those symptoms that are drug-responsive, some of which are not included in current diagnostic criteria. Patients with borderline and schizotypal disorder without the foregoing symptoms probably would not profit from thiothixene and might needlessly be placed at risk for adverse drug effects.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder.

Borderline personality disorder is characterized by affective instability, impulsivity, and aggression and is associated with considerable morbidity and mortality. Since anticonvulsant agents may be helpful in such symptomatology, we compared divalproex sodium with placebo in patients with borderline personality disorder. A 10-week, parallel, double-blind design was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM-IV Axis II Personality Disorders criteria for borderline personality disorder were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12). Change was assessed in global symptom severity (Clinical Global Impressions-Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as well as in specific core symptoms (depression, aggression, irritability, and suicidality). There was significant improvement from baseline in both global measures (CGI-I and GAS) following divalproex sodium treatment. A high dropout rate precluded finding significant differences between the treatment groups in the intent-to-treat analyses, although all results were in the predicted direction. Treatment with divalproex sodium may be more effective than placebo for global symptomatology, level of functioning, aggression, and depression. Controlled trials with larger sample sizes are warranted to confirm these preliminary results.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study.

Aripiprazole is a relatively new atypical antipsychotic agent that has been successfully employed in therapy for schizophrenia and schizoaffective disorders. A few neuroleptics have been used in therapy for patients with borderline personality disorder, which is associated with severe psychopathological symptoms. Aripiprazole, however, has not yet been tested for this disorder, and the goal of this study was to determine whether aripiprazole is effective in the treatment of several domains of symptoms of borderline personality disorder. Subjects meeting criteria for the Structured Clinical Interview for DSM-III-R Personality Disorders for borderline personality disorder (43 women and 9 men) were randomly assigned in a 1:1 ratio to 15 mg/day of aripiprazole (N=26) or placebo (N=26) for 8 weeks. Primary outcome measures were changes in scores on the symptom checklist (SCL-90-R), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and the State-Trait Anger Expression Inventory and were assessed weekly. Side effects and self-injury were assessed with a nonvalidated questionnaire. According to the intent-to-treat principle, significant changes in scores on most scales of the SCL-90-R, the HAM-D, the HAM-A, and all scales of the State-Trait Anger Expression Inventory were observed in the subjects treated with aripiprazole after 8 weeks. Self-injury occurred in the groups. The reported side effects were headache, insomnia, nausea, numbness, constipation, and anxiety. Aripiprazole appears to be a safe and effective agent in the treatment of patients with borderline personality disorder.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study.

Anger and aggression are typical in borderline patients. The goal of this study was to compare the efficacy of lamotrigine versus placebo in the treatment of aggression in women meeting the criteria for borderline personality disorder (BPD). We conducted a randomized, double-blind, placebo-controlled study of lamotrigine in 24 female subjects meeting Structured Clinical Interview for DSM-IV (SCID) criteria for BPD. The subjects were randomly assigned in a 2: 1 manner ratio to lamotrigine (n = 18) or placebo (n = 9). Treatment duration was 8 weeks. Primary outcome measures were self-reported changes on the anger scales of the Trait Anger Expression Inventory (STAXI). In comparison with the placebo group, and according to the intention-to-treat principle, highly significant (p < 0.01) changes on four STAXI scales (State-Anger, Trait-Anger, Anger-Out, Anger-Control) were observed in those subjects treated with lamotrigine after 8 weeks. The only exception (p < 0.05) was found on the Anger-In scale, where a difference of only 8.5% (p < 0.2) was found. All the patients tolerated lamotrigine relatively well. Lamotrigine appears to be a safe and effective agent in the treatment of anger in women with criteria-defined BPD as defined by SCID criteria. It did not produce any clinically significant effect on body weight.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Topiramate treatment of aggression in female borderline personality disorder patients: a double-blind, placebo-controlled study.

The goal of this study was to compare the efficacy and safety of topiramate versus placebo in the treatment of aggression in women who meet the criteria for borderline personality disorder. We conducted a double-blind, placebo-controlled study of topiramate in 29 female subjects (response rate 93.5%) meeting SCID (Structured Clinical Interview for DSM-IV) criteria for borderline personality disorder. The subjects were randomly assigned in a 2:1 ratio to topiramate (N = 21, analysis based on N = 19) or placebo (N = 10). Treatment lasted 8 weeks (November 2003-January 2004). Primary outcome measures were self-reported changes on the anger subscales of the State-Trait Anger Expression Inventory (STAXI). Significant improvements on 4 subscales of the STAXI (state-anger, trait-anger, anger-out, anger-control) were observed in the topiramate-treated subjects after 8 weeks, in comparison with the placebo group. The difference in improvement in score between the 2 groups for state-anger, trait-anger, and anger-out ranged from 21% to 24%, and the difference for anger-control was -13%. As an exception, a difference of only 8.5% (p < .2) was found on the anger-in subscale. Significantly greater weight loss was observed in the topiramate-treated group than in those treated with placebo (difference in weight loss between the 2 groups: 2.3 kg [5.1 lb] [3.2%]; 95% CI = 1.3% to 4.4%, p < .01). All patients tolerated topiramate well. Topiramate appears to be a safe and effective agent in the treatment of anger in women with borderline personality disorder as defined by SCID criteria. Additionally, significant weight loss can be expected.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

SSRI treatment of borderline personality disorder: a randomized, placebo-controlled clinical trial for female patients with borderline personality disorder.

Selective serotonin reuptake inhibitors (SSRIs) are recommended for treatment of affect lability, impulsivity, and aggression in patients with borderline personality disorder. This recommendation is based on positive findings in at least 10 open studies and one small double-blind study of SSRIs for patients with borderline personality disorder and one study of impulsive aggressive patients with different personality disorders. A randomized, placebo-controlled SSRI study with borderline personality disorder patients, however, provided inconclusive results because of a large response to placebo. It was, therefore, decided to conduct a new randomized trial with a larger study group. A double-blind, placebo-controlled, randomized trial using the SSRI fluvoxamine for 6 weeks followed by a blind half-crossover for 6 weeks and an open follow-up for another 12 weeks was conducted with 38 nonschizophrenic, nonbipolar female patients with borderline personality disorder. The outcome measures were the rapid mood shift, impulsivity, and aggression subscales from the Borderline Personality Disorder Severity Index. Fluvoxamine but not placebo produced a robust and long-lasting reduction in the scores on the subscale for rapid mood shifts. In contrast, no difference between the fluvoxamine and placebo groups was observed in the effect on the impulsivity and aggression scores. In this study, fluvoxamine significantly improved rapid mood shifts in female borderline patients, but not impulsivity and aggression. This latter finding may be due to gender-specific differences in impulsivity and aggression.

CD005653

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

A trial of carbamazepine in borderline personality disorder.

Borderline personality disorder does not have a first choice pharmacological treatment. We studied 20 borderline inpatients in a double-blind parallel placebo-controlled trial with carbamazepine for a mean of 30.9 days. No significant positive effects of the drug were found.

CD002170

In patients with stable COPD, pMDI produced similar outcomes to a dry powder device for delivering beta2-agonists, but the very small number of studies and included patients does not permit firm conclusions to be drawn. The soft mist device for ipratropium was more effective than a pMDI, but the data come from one small study. There need to be further well designed randomised controlled trials to define the role of inhaler devices using bronchodilators in stable COPD.

Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.

The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.

CD002170

In patients with stable COPD, pMDI produced similar outcomes to a dry powder device for delivering beta2-agonists, but the very small number of studies and included patients does not permit firm conclusions to be drawn. The soft mist device for ipratropium was more effective than a pMDI, but the data come from one small study. There need to be further well designed randomised controlled trials to define the role of inhaler devices using bronchodilators in stable COPD.

Improved delivery of ipratropium bromide using Respimat (a new soft mist inhaler) compared with a conventional metered dose inhaler: cumulative dose response study in patients with COPD.

Respimat (RMT) is a reusable, propellant-free, soft mist inhaler (SMI), a novel device for inhalation therapy. We conducted a three-period cross-over study to evaluate the safety and efficacy of cumulative doses of ipratropium bromide inhaled from RMT (Two dose levels) or from a pressurized metered dose inhaler (MDI), in 36 patients with chronic obstructive pulmonary disease (COPD). The bronchodilator effect of ipratropium bromide was greater when administered via RMT (10 or 20 microg per puff, given double-blind within device, to total doses of 160 or 320 microg) than via MDI (20 microg per puff, total dose 320 microg). The bronchodilator effects of the 160 and 320 microg doses delivered via RMT were similar. Cumulative ipratropium bromide doses of 320 microg given via MDI or RMT and 160 microg given via RMT produced similar safety profiles. Between 45 min after the first drug inhalation and 45 min after the final dose, greater bronchodilatory effect was obtained from half the cumulative dose of ipratropium (RMT 10 microg per puff) when compared with the MDI (20 microg per puff). Therefore, ipratropium bromide delivered by RMT is as safe as, and can be more effective than, the MDI on acute administration in patients with COPD.

CD002170

In patients with stable COPD, pMDI produced similar outcomes to a dry powder device for delivering beta2-agonists, but the very small number of studies and included patients does not permit firm conclusions to be drawn. The soft mist device for ipratropium was more effective than a pMDI, but the data come from one small study. There need to be further well designed randomised controlled trials to define the role of inhaler devices using bronchodilators in stable COPD.

Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler.

Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

The diagnostic contribution of the frontal lumbar spine radiograph in community referred low back pain--a prospective study of 1030 patients.

The diagnostic contribution of the anteroposterior (AP) view was studied to assess whether this view could be omitted safely, thus reducing the radiation burden received by patients undergoing lumbar spine radiography. Prospective analysis of 1030 consecutive referrals for lumbar spine radiography from general practice. In the majority of cases (90.5%) the AP view was non-contributory. In 4.2% the diagnosis was strengthened and it was altered in 4.6%. However, in the latter group only 1.3% of the total were considered significant alterations. These were cases of possible, but not definite, pars defects and sacroiliitis. Specific important conditions such as infection, malignancy and benign tumours were not missed on the lateral view alone, in our study population. The radiation burden is reduced by 75% by omitting the AP view. A single lateral view is an adequate examination, with the proviso that sacroiliac joint disease is not assessed on this view and some pars defects and facet joint degenerative changes may be overlooked. The radiation protection gains are considerable. A single lateral lumbar view is now our routine practice unless sacroiliitis is a specific clinical concern.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Selective criteria may increase lumbosacral spine roentgenogram use in acute low-back pain.

Eleven clinical criteria have been proposed to limit use of lumbosacral spine roentgenograms in patients with acute low-back pain who are at risk for vertebral cancer, osteomyelitis, acute fracture, or herniated disk. We retrospectively applied the criteria to 471 patients with acute low-back pain in three teaching hospital walk-in clinics. Roentgenograms were obtained at the initial visit in 99 patients (21.1%); the number would have increased to 217 (46.1%) if the criteria had been used. The following four patient characteristics were associated with actual roentgenogram use: older age, longer duration of symptoms, reflex asymmetry, and point vertebral tenderness. Adoption of the 11 criteria studied herein may inadvertently increase roentgenogram use, thereby raising health care costs and exposing more patients to gonadal irradiation. The standard of practice in these three clinics seemed to entail use of less broad roentgenogram selection criteria. Other published guidelines for roentgenograms emphasize clinical follow-up, reserving further evaluation for patients who fail to improve after a trial of bed rest and analgesics.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Evaluating the accuracy of a simple heuristic to identify serious causes of low back pain.

Among patients presenting with low back pain (LBP), GPs have to identify those with serious, treatable conditions. However, excluding these conditions in every patient with LPB is time consuming and of low yield. We have suggested that identifying those patients where these serious conditions need to be considered can be made more efficient through asking patient if they feel their LBP is new or unfamiliar in some way. To evaluate the diagnostic validity of a simple heuristic based on the patient's view of the familiarity of LBP. Cross-sectional diagnostic study with delayed-type reference standard, nested within a three-arm randomized trial of quality improvement for LBP. A total of 1378 patients presenting, with LBP, to one of 126 participating GPs were included. They were asked whether their LBP was familiar or not (index test). At 1 year, patients were interviewed with regard to relevant conditions that in hindsight might explain their LBP. Reviewers deciding on disease status (reference standard) were blinded to the results of the index test. Totally 1190 patients answered the index test question and were available for interview at 1 year. Only four of these had a serious cause of their LBP. Two of these were identified by the familiarity heuristic, resulting in low sensitivity. The number of diseased patients was too small to obtain a reliable estimate of sensitivity. Low prevalence of serious disease in primary care poses difficulties for diagnostic research. In hindsight we would question whether an RCT-setting emphasizing non-specific LBP is suitable for this kind of research. At present, the familiarity heuristic cannot be recommended for patients presenting with LBP.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Use of lumbosacral spine radiographs in a level II emergency department.

We studied indications for lumbosacral spine radiographs in an emergency department setting. Clinicians completed a lumbosacral spine request form before obtaining lumbosacral radiographs on 482 patients who were examined in a level II emergency department. The clinicians detailed the indications for the examination, their suspected clinical diagnoses, and the expected effect of the lumbosacral spine study on management. In addition, the duration of the patients' symptoms was recorded as well as their age and sex. These data were compared with the actual radiographic findings as interpreted by board-certified musculoskeletal radiologists. Major indications for lumbosacral radiographs were lower back pain (92%) and trauma (36%). Patient expectation and medicolegal concerns, related either to insurance documentation or to physician litigation, were cited in 42% of cases. A neurologic deficit was present in 88% of patients, and a history of neoplasm was elicited in 4%. Strain (56%) and fracture (20%) were the most commonly suspected clinical diagnoses. Radiographs showed either normal findings or spondylosis in 86% of cases. Fractures, of which 10 were definitely acute, were identified in 55 patients. No fracture required decompression. Neoplastic involvement was found in seven patients, all of whom had histories of osseous metastases. Neurologic deficit, present in 37 patients, did not correlate with abnormalities seen on lumbosacral radiographs. As with studies of lumbosacral spine radiographs obtained in outpatient settings, our data from a level II emergency department support the use of lumbosacral spine radiographs for patients with a history of trauma, even if relatively minor, in elderly patients and in patients with lower back pain who have a history of neoplasm. Lumbosacral radiographs obtained for an isolated complaint of lower back pain generally provide no clinically useful information. Similarly, lumbosacral radiographs obtained for patients with isolated neurologic abnormalities are unrevealing. Such patients are better examined (although not necessarily at the time of emergency department evaluation) with techniques such as MR imaging that show soft-tissue lesions.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Musculoskeletal pain as an indicator of occult malignancy. Yield of bone scintigraphy.

When musculoskeletal pain is persistent or out of proportion to clinical findings, diagnostic imaging is often used to evaluate for the presence of occult pathologic conditions. To examine the efficacy of bone scintigraphy for identifying occult malignancy in such patients. Bone scans of 491 patients with new or recurrent complaints of musculoskeletal pain and no previously known malignancy were retrospectively reviewed. The findings of each scan were classified into 1 of the following categories: (A) no evidence of malignancy; (B) equivocal (1-3 lesions of uncertain significance); or (C) probable metastatic disease (> 3 lesions without trauma or other benign explanation). All diagnoses of malignancy established within 6 months of the bone scan were then determined from review of radiological and clinical records. The distribution of scan interpretations was as follows: category A, 386 (79%); category B, 84 (17%); and category C, 21 (4%). Among the 181 patients younger than 50 years, 161 (89%) had category A and 20 (11%) had category B scans. Of the 310 patients aged 50 years or older, 226 (73%) had scans in category A, 64 (21%) in category B, and 21 (7%) in category C. Thirty patients (6%) had malignancy involving bone, 29 among those aged 50 years or older. In patients aged 50 years or older, 10 (16%) of 64 with equivocal scan findings (category B) and 19 (90%) of 21 with widespread abnormalities (category C) had malignancy involving bone. Initial radiographs of symptomatic sites showed lytic or blastic bone abnormalities suggestive of malignancy in 16 (59%) of the 29 older patients in whom this diagnosis was confirmed. In patients aged 50 years or older, the yield of bone scintigraphy for identification of occult malignancy (29/310; 9%) is sufficient to justify its use in the investigation of the cause of problematic bone or musculoskeletal symptoms.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain.

To determine the prevalence of serious pathology in patients presenting to primary care settings with acute low back pain, and to evaluate the diagnostic accuracy of recommended "red flag" screening questions. An inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney, Australia. At the initial consultation, clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis. The reference standard was a 12-month followup supplemented with a specialist review of a random subsample of participants. There were 11 cases (0.9%) of serious pathology, including 8 cases of fracture. Despite the low prevalence of serious pathology, most patients (80.4%) had at least 1 red flag (median 2, interquartile range 1-3). Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative: prolonged use of corticosteroids, age >70 years, and significant trauma. Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false-positive diagnoses. The status of a diagnostic prediction rule containing 4 features (female sex, age >70 years, significant trauma, and prolonged use of corticosteroids) was moderately associated with the presence of fracture (the area under the curve for the rule score was 0.834 [95% confidence interval 0.654-1.014]; P = 0.001). In patients presenting to a primary care provider with back pain, previously undiagnosed serious pathology is rare. The most common serious pathology observed was vertebral fracture. Approximately half of the cases of serious pathology were identified at the initial consultation. Some red flags have very high false-positive rates, indicating that, when used in isolation, they have little diagnostic value in the primary care setting.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Cancer as a cause of back pain: frequency, clinical presentation, and diagnostic strategies.

Back pain is very common. Rarely, it may be the first manifestation of cancer. Although many advocate selective use of laboratory and x-ray tests for back pain patients, the early detection of cancer may be an important reason to obtain such tests. To develop a diagnostic approach that would identify malignancies while remaining parsimonious, the authors evaluated 1,975 walk-in patients with a chief complaint of back pain. Thirteen patients (0.66%) proved to have underlying cancer. Findings significantly associated with underlying cancer (p less than 0.05) were: age greater than or equal to 50 years, previous history of cancer, duration of pain greater than 1 month, failure to improve with conservative therapy, elevated erythrocyte sedimentation rate (ESR), and anemia. Combining historical features and ESR results led to an algorithm that would have limited x-ray utilization to just 22% of subjects while recommending an x-ray for every cancer patient. It would further suggest which patients with negative x-ray findings require further work-up.

CD008686

For most "red flags," there is insufficient evidence to provide recommendations regarding their diagnostic accuracy or usefulness for detecting spinal malignancy. The available evidence indicates that in patients with LBP, an indication of spinal malignancy should not be based on the results of one single "red flag" question. Further research to evaluate the performance of different combinations of tests is recommended.

Lumbar spine films in primary care: current use and effects of selective ordering criteria.

Low back pain (LBP) often prompts radiography, although the diagnostic yield of lumbar spine films is low, and many radiographic abnormalities are unrelated to symptoms. Criteria have been proposed for selective x-ray use, but their value and safety are uncertain. To evaluate these criteria, the authors prospectively studied 621 walk-in patients with LBP. The yield of explanatory x-ray findings was over three times greater among patients with indications for radiography than among those without. Furthermore, an indication for x-rays existed for all patients found to have a malignancy, and for 13 of 14 patients with an identified fracture. Actual physician ordering, however, did not correspond well with the recommended indications. Application of selective criteria appears safe and may improve the yield of useful findings. It may not, however, reduce x-ray utilization from current levels without further refinement in the criteria.

CD006182

Evidence from two RCTs suggests no significant benefits or harms of peritoneal drainage over laparotomy. However, due to the very small sample size, clinically significant differences may have easily been missed. No firm recommendations can be made for clinicians. Large multicentre randomised controlled trials are needed to address this question definitively.

Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation.

Perforated necrotizing enterocolitis is a major cause of morbidity and mortality in premature infants, and the optimal treatment is uncertain. We designed this multicenter randomized trial to compare outcomes of primary peritoneal drainage with laparotomy and bowel resection in preterm infants with perforated necrotizing enterocolitis. We randomly assigned 117 preterm infants (delivered before 34 weeks of gestation) with birth weights less than 1500 g and perforated necrotizing enterocolitis at 15 pediatric centers to undergo primary peritoneal drainage or laparotomy with bowel resection. Postoperative care was standardized. The primary outcome was survival at 90 days postoperatively. Secondary outcomes included dependence on parenteral nutrition 90 days postoperatively and length of hospital stay. At 90 days postoperatively, 19 of 55 infants assigned to primary peritoneal drainage had died (34.5 percent), as compared with 22 of 62 infants assigned to laparotomy (35.5 percent, P=0.92). The percentages of infants who depended on total parenteral nutrition were 17 of 36 (47.2 percent) in the peritoneal-drainage group and 16 of 40 (40.0 percent) in the laparotomy group (P=0.53). The mean (+/-SD) length of hospitalization for the 76 infants who were alive 90 days after operation was similar in the primary peritoneal-drainage and laparotomy groups (126+/-58 days and 116+/-56 days, respectively; P=0.43). Subgroup analyses stratified according to the presence or absence of radiographic evidence of extensive necrotizing enterocolitis (pneumatosis intestinalis), gestational age of less than 25 weeks, and serum pH less than 7.30 at presentation showed no significant advantage of either treatment in any group. The type of operation performed for perforated necrotizing enterocolitis does not influence survival or other clinically important early outcomes in preterm infants. (ClinicalTrials.gov number, NCT00252681.). Copyright 2006 Massachusetts Medical Society.

CD006182

Evidence from two RCTs suggests no significant benefits or harms of peritoneal drainage over laparotomy. However, due to the very small sample size, clinically significant differences may have easily been missed. No firm recommendations can be made for clinicians. Large multicentre randomised controlled trials are needed to address this question definitively.

Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial.

To determine whether primary peritoneal drainage improves survival and outcome of extremely low birth weight (ELBW) infants with intestinal perforation. Optimal surgical management of ELBW infants with intestinal perforation is unknown. An international multicenter randomized controlled trial was performed between 2002 and 2006. Inclusion criteria were birthweight >or=1000 g and pneumoperitoneum on x-ray (necrotizing enterocolitis or isolated perforation). Patients were randomized to peritoneal drain or laparotomy, minimizing differences in weight, gestation, ventilation, inotropes, platelets, country, and on-site surgical facilities. Patients randomized to drain were allowed to have a delayed laparotomy after at least 12 hours of no clinical improvement. Sixty-nine patients were randomized (35 drain, 34 laparotomy); 1 subsequently withdrew consent. Six-month survival was 18/35 (51.4%) with a drain and 21/33 (63.6%) with laparotomy (P = 0.3; difference 12% 95% CI, -11, 34%). Cox regression analysis showed no significant difference between groups (hazard ratio for primary drain 1.6; P = 0.3; 95% CI, 0.7-3.4). Delayed laparotomy was performed in 26/35 (74%) patients after a median of 2.5 days (range, 0.4-21) and did not improve 6-month survival compared with primary laparotomy (relative risk of mortality 1.4; P = 0.4; 95% CI, 0.6-3.4). Drain was effective as a definitive treatment in only 4/35 (11%) surviving neonates, the rest either had a delayed laparotomy or died. Seventy-four percent of neonates treated with primary peritoneal drainage required delayed laparotomy. There were no significant differences in outcomes between the 2 randomization groups. Primary peritoneal drainage is ineffective as either a temporising measure or definitive treatment. If a drain is inserted, a timely "rescue" laparotomy should be considered. Trial registration number ISRCTN18282954; http://isrctn.org/

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

PTFE bypass to below-knee arteries: distal vein collar or not? A prospective randomised multicentre study.

Patency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study. Patients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups - bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first. In the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%). At 3 years, primary patency was 26% (95% confidence interval (CI) 18-38) with a vein collar and 43 (33-58) without a vein collar for femoro-popliteal bypass and 20 (11-38), and 17 (9-33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54-75) and 61 (50-74) for femoro-popliteal bypass, and 59 (46-76) and 44 (32-61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan-Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage. This study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery. Copyright (c) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

Multicenter randomized prospective trial comparing a pre-cuffed polytetrafluoroethylene graft to a vein cuffed polytetrafluoroethylene graft for infragenicular arterial bypass.

Poor patency of synthetic grafts for infragenicular revascularization has led to use of distal vein patches or cuffs. The aim of this study was to compare the distally widened Distaflo PTFE graft, which mimics a vein cuff, with a PTFE graft with distal vein modification. In this prospective, randomized, multicenter trial we compared use of a precuffed PTFE graft wit that of PTFE grafts with distal vein modification for infragenicular revascularization in patients with critical limb ischemia without saphenous vein. Study end points were primary and secondary patency and limb salvage rates at 2 years. From January 28,1999 to November 1, 2000, 104 patients were enrolled in 10 North American centers. Thirteen were excluded for protocol violation. Ninety-one bypasses were performed in 89 patients with a mean age of 73 years (range 47-90). By randomization, 47 bypasses were done with the precuffed graft and 44 with PTFE graft with vein cuff. Both groups were comparable for comorbidities and operative variables, except for a higher incidence of acute ischemia in the precuffed group (19% vs. 4.5%, p = 0.03). Bypass was a redo procedure in 53% and was performed at the infrapopliteal vessels in 79%. Operative mortality was 2.2% (2/91). Mean follow-up was 14 months (range 1-30). At 1 and 2 years, primary patency was 52% and 49% for the precuffed group and 62% and 44% for the vein cuffed group, respectively (p = 0.53). At 1 year and 2 years, the limb salvage rate was 72% and 65% for the precuffed group and 75% and 62% in the vein cuffed group (p = 0.88). Although numbers are small and follow-up short, this midterm analysis shows similar results for the Distaflo precuffed grafts and PTFE grafts with vein cuff. A precuffed graft is a reasonable alternative conduit for infragenicular reconstruction in the absence of saphenous vein and provides favorable limb salvage.

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

Prospective randomised trial of distal arteriovenous fistula as an adjunct to femoro-infrapopliteal PTFE bypass.

To compare graft patency and limb salvage rate following femoro-infrapopliteal bypass using ePTFE grafts with and without the addition of adjuvant arterio-venous fistula. A prospectively randomised controlled trial. Patients referred to two teaching hospital vascular surgery units in the U.K. for the treatment of critical limb ischaemia. Eighty-seven patients (M:F; 2.3:1) undergoing 89 femoro-intrapopliteal bypass operations with ePTFE grafts for critical limb ischaemia were randomly allocated to have AVF included in the operative procedure (n = 48) or to a control group without AVF (n = 41). An interposition vein-cuff was incorporated at the distal anastomosis in all patients. The cumulative rates of primary patency and limb salvage at 1-year after operation for patients with AVF were 55.2% and 54.1% compared to 53.4% and 43.2%, respectively, for the control group. The differences between the AVF and control groups did not reach statistical significance, in terms of either graft patency or limb salvage, at any stage after operation (Log-Rank test). AVF confers no additional significant clinical advantage over interposition vein cuff in patients having femoro-infrapopliteal bypass with ePTFE grants for critical limb ischaemia.

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

Early results of a prospective randomized trial of spliced vein versus polytetrafluoroethylene graft with a distal vein cuff for limb-threatening ischemia.

Single-piece vein remains the conduit of choice in patients who need bypass grafting for limb salvage. When this option is not available, two of the remaining options are prosthetic bypass graft or several segments of vein spliced together. In this study, we compare spliced vein bypass grafting versus polytetrafluoroethylene grafting with a distal vein cuff in patients with limb-threatening ischemia. Between 1996 and 2000, 39 bypass grafting procedures in 36 patients were performed for limb-threatening ischemia. These procedures were prospectively randomized to either spliced vein bypass grafting (spliced group, 19 bypass grafts) or polytetrafluoroethylene grafting with a distal vein cuff (cuff group, 20 bypass grafts). All the patients in the cuff group underwent anticoagulation therapy with warfarin sodium after surgery. The inclusion criteria included: no single-piece vein option for bypass grafting, adequate vein for splice, no composite sequential option, and limb-threatening ischemia. The demographics were similar between the two groups. The primary patency rate at 2 years was 44% and 49% for the spliced and cuff groups, respectively. In the spliced group, seven of 19 bypass grafts underwent revision in the follow-up period, and two of 20 cuffed bypass grafts were successfully revised. The secondary patency rate was 87% and 59% (P <.05), with limb salvage rates of 94% and 85% for spliced and cuff groups, respectively. Four patients in the spliced vein group needed reoperation for wound complications related to vein harvest. One polytetrafluoroethylene graft needed removal for infection. Two early mortalities occurred in the spliced group, one from myocardial infarction and one from stroke. The overall survival rate at 2 years between the two groups was 67% and 100% for the spliced and cuff groups, respectively (P <.05). Although this is a preliminary report, it appears that both spliced vein bypass grafting and polytetrafluoroethylene bypass grafting with a distal vein cuff produce acceptable limb salvage rates. The secondary patency rate for spliced vein is better, but these bypass grafts more often need revision or reoperation for wound complications.

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

Randomized trial comparing infrainguinal polytetrafluoroethylene bypass grafting with and without vein interposition cuff at the distal anastomosis. The Joint Vascular Research Group.

A multicenter randomized prospective study was undertaken to determine whether an interposition vein cuff improved the short-term and medium-term patency and limb salvage rates of femoral-above-knee and femoral-below-knee popliteal artery polytetrafluoroethylene (PTFE) bypass procedures. Two hundred sixty-one bypass operations were randomized (133 to vein cuff and 128 to no vein cuff). One hundred fifty grafts were to the above-knee popliteal artery, 96 to the below-knee popliteal artery, and 15 to tibial vessels. The median follow-up was 617 days. The 12-month patency rates for cuffed and uncuffed above-knee popliteal artery PTFE bypass grafts were 80% and 84%, and the 2-year patency rates were 72% and 70%, respectively. The patency rates for bypass grafts to the below-knee popliteal artery at 12 months were 80% and 65% and at 2 years 52% and 29%, respectively (p = 0.03). At the below-knee site, this was reflected in 24-month difference in limb salvage rates of 84% and 62%, respectively (p = 0.08). There was no improvement in the patency rate with the use of a distal anastomosis interposition vein cuff in femoral-above-knee popliteal PTFE bypass grafts, but there was a statistically significant advantage when PTFE bypass grafts were anastomosed to the popliteal artery below the knee.

CD007921

There is some evidence that a vein cuff at the distal anastomosis site improves primary graft patency rates for below knee PTFE graft, but this does not reduce the risk of limb loss. Evidence for this beneficial effect of vein cuffed PTFE grafts is weak and based on an underpowered trial. Pre-cuffed PTFE grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts. The use of spliced veins improved secondary patency but this did not translate into improved limb salvage. The use of an AVF alone showed no added benefits. A large study with a specific focus on below knee vein cuff prosthetic grafts, including PTFE, is required.

Does an adjuvant AV-fistula improve the patency of a femorocrural PTFE bypass with distal vein cuff in critical leg ischaemia?--a prospective randomised multicentre trial.

A lack of suitable veins can cause serious problems when attempting to revascularise critically ischaemic legs. Prosthetic grafts have much worse patency in the femocrural position, despite the use of distal anastomotic cuffs. The use of adjuvant AV-fistula at the distal anastomosis should increase the graft flow above the thrombotic threshold velocity and thus increase prosthetic graft patency. The aim of the study was to evaluate the benefit of an adjuvant AV-fistula on the patency of a femorocrural PTFE bypass with a distal vein cuff. This prospective randomised multicentre trial was conducted in four centres. A total of 59 patients with critical leg ischaemia and no suitable veins for grafting were randomised to receive a femocrural PTFE bypass and distal vein cuff, with or without an adjuvant AV-fistula. Thirty-one patients were randomised to the AV-fistula group (AVFG) and 28 to the control group (CG). Six patients were lost to follow-up during the 2-year study time. There were six immediate occlusions in each treatment group, but half of these were saved by re-operation. The mean postoperative ankle-brachial index (ABI) was 0.85 in the AVFG and 0.94 in the CG. The primary and secondary patency rate at 2 years was 29 and 40% for the AVFG and 36 and 40% for the CG (NS). Leg salvage at 2 years was 65 and 68%, respectively (NS). Adjuvant AV-fistula does not improve the patency of a femorocrural PTFE bypass with a distal vein cuff.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Randomized trial of ciprofloxacin compared with other antimicrobial therapy in the treatment of osteomyelitis.

Thirty adults (mean age, 52 years) were enrolled in a randomized, comparative trial of oral ciprofloxacin (750 mg twice daily) and other antimicrobial therapies. Etiologic agents included Enterobacteriaceae (18 isolates), Pseudomonas aeruginosa (16 isolates), and Staphylococcus aureus (four isolates). Seven of 14 (50 percent) ciprofloxacin-treated infections are cured at up to 13 months follow-up and three infections appear improved. Treatment failure or relapse has occurred in four patients. Sixteen patients received other antimicrobial therapy and 11 patients (65 percent) remain without infection and have healed wounds, with follow-up from one to 13 months. One patient has had a relapse, while improvement is apparent in four patients. Complications that occurred in this group included drug-related neutropenia (two patients), diarrhea (two patients), drug allergy (one patient), and catheter-related staphylococcal cellulitis (one patient). Oral ciprofloxacin therapy for chronic osteomyelitis caused by susceptible organisms appears to be as effective as other antimicrobial therapies.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Oral ciprofloxacin compared with parenteral antibiotics in the treatment of osteomyelitis.

We undertook a prospective, randomized comparison of oral ciprofloxacin with standard parenteral therapies for the treatment of biopsy-proven osteomyelitis caused by susceptible organisms. Following surgical debridement, the ciprofloxacin patients received 750 mg twice a day, and the other patients received a broad-spectrum cephalosporin or a nafcillin-aminoglycoside combination intravenously (i.v.). There were 31 evaluable patients in the ciprofloxacin group, treated an average of 56 days, and 28 in the i.v. group, treated an average of 47 days. Clinical success rates were 24 of 31 (77%) for the ciprofloxacin group and 22 of 28 (79%) for the i.v. group. Of the seven failures in the ciprofloxacin group, one was due to a persistent Klebsiella pneumoniae infection and six were due to relapse of the infection within 1 year of therapy. Of the six failures in the i.v. group, one was due to an Enterobacter aerogenes strain which emerged resistant and five were due to relapse. The most troublesome etiology was polymicrobial osteomyelitis involving Pseudomonas aeruginosa, in which five of six (83%) regimens failed. Adverse reactions occurred infrequently, i.e., in 1 of 31 (3%) of the ciprofloxacin patients and in 4 of 28 (14%) of the i.v. patients, yet all reactions responded to therapy and none required protocol deviation. Our data indicate that oral ciprofloxacin monotherapy is as safe and effective as conventional parenteral therapy in cases of osteomyelitis caused by susceptible organisms.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Ofloxacin versus parenteral therapy for chronic osteomyelitis.

We conducted a randomized comparison of oral ofloxacin (400 mg twice a day) and parenteral agents (cefazolin, 1.0 g intravenously every 8 h, or ceftazidime, 2.0 g intravenously every 12 h) in biopsy-confirmed, nonprosthesis osteomyelitis. A total of 19 subjects received ofloxacin for an average of 8 weeks, and 14 received parenteral antibiotics for an average of 4 weeks; both therapies were well tolerated. Infections were due to Staphylococcus aureus (40%), Enterococcus spp. (3%), Pseudomonas aeruginosa (15%), and other gram-negative organisms (42%). At the completion of therapy, one P. aeruginosa infection in the ofloxacin group persisted and the organism acquired resistance, accompanied by a resistant Acinetobacter superinfection. In the parenteral group, one S. aureus infection persisted, and there was a resolved superinfection due to S. aureus as well. Eighteen-month follow-up data have been obtained. Among those treated with ofloxacin, four subjects whose initial response to therapy was successful suffered relapses of infection, three due to S. aureus and one due to P. aeruginosa, while in the parenteral group, one subject with a P. aeruginosa infection relapsed. Long-term response to therapy was successful for 14 of 19 (74%) subjects who received ofloxacin and 12 of 14 (86%) who received parenteral antibiotics; the difference was not significant. Oral ofloxacin appears comparable to parenteral antibiotics in chronic osteomyelitis due to susceptible organisms, and oral ofloxacin offers advantages in economics and convenience.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Oral ciprofloxacin compared with standard parenteral antibiotic therapy for chronic osteomyelitis in adults.

A group of fourteen patients who had chronic osteomyelitis and were treated with oral ciprofloxacin was compared with a group of twelve patients of similar age who had chronic osteomyelitis and received standard parenteral antibiotic therapy consisting of nafcillin, clindamycin, and gentamicin, singly or in combination. The osteomyelitis was arrested at the end of therapy and on follow-up examination of eleven patients in the first group and ten in the second group. The average duration of antibiotic therapy (thirty-eight days) and follow-up (approximately thirty months) were about the same for both groups. Oral administration of ciprofloxacin was as effective and safe as parenteral therapy for the treatment of osteomyelitis in these adults.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Chronic osteomyelitis caused by Staphylococcus aureus: controlled clinical trial of nafcillin therapy and nafcillin-rifampin therapy.

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis.

The efficacy and safety of three oral fluoroquinolones (lomefloxacin, levofloxacin, and ciprofloxacin) for the treatment of chronic osteomyelitis were analyzed. Twenty-seven patients had documented infections with quinolone-sensitive organisms and received either lomefloxacin, levofloxacin, or ciprofloxacin. Levofloxacin was effective therapy for 9 of 15 (60%) patients. Lomefloxacin was effective therapy for five of seven (71%) patients, and ciprofloxacin was effective therapy for two of five patients (40%). Average follow-up was 11.8 months for patients who completed the course of therapy, and the average duration of therapy was 60.6 days. Gram-positive bacteria were isolated from 18 patients, and 11 patients were cured. Oral fluoroquinolones can be safe, effective therapy if they are given for a prolonged course as treatment for infections caused by susceptible gram-positive as well as gram-negative organisms and in combination with adequate surgical debridement.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Randomized evaluation of ceftazidime or ticarcillin and tobramycin for the treatment of osteomyelitis caused by gram-negative bacilli.

Ceftazidime, a new cephalosporin with enhanced activity against aerobic gram-negative bacilli, was compared with tobramycin and ticarcillin in a randomized clinical trial. Efficacy and safety were evaluated in 18 patients (17 males, 1 female) with gram-negative osteomyelitis. All organisms were susceptible to the treatment antibiotics(s). There were nine patients treated with tobramycin and ticarcillin for 27 to 62 days (mean, 42 days), and nine patients were treated with 4 g of ceftazidime per day for 26 to 63 days (mean, 45 days). All nine patients receiving tobramycin and ticarcillin had the osteomyelitis arrested after the initial treatment. Follow-up was for 2 to 38 months (mean, 22 months). Of nine patients receiving ceftazidime three were initial treatment failures. Follow-up was for 13 to 31 months (mean, 21 months). A patient receiving ceftazidime had a transient rise in serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase. There were three treatment failures in the ceftazidime group; no failures occurred in the group receiving the combination of ticarcillin and tobramycin. A larger series would be required to detect a significant difference between the two treatment groups.

CD004439

Limited evidence suggests that the method of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are sensitive to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.

Oral ofloxacin versus parenteral imipenem-cilastatin in the treatment of osteomyelitis.

We conducted a prospective, randomized, open-label trial, comparing oral ofloxacin with intravenous imipenem-cilastatin for the treatment of chronic osteomyelitis in order to evaluate the efficacy and tolerance. Hospitalized patients with diagnosis of chronic osteomyelitis and isolation of susceptible organisms to ofloxacin and imipenem/cilastatin were eligible for enrollment. Ofloxacin was administered orally (400 mg every 12 hours), and imipenem-cilastatin was given intravenously (500 mg every 6 hours). Organisms were considered susceptible to ofloxacin when the minimal inhibitory concentration (MIC) was <2 micrograms/ml, and to imipenem-cilastatin when the MIC was <4 micrograms/ml. Thirty-two patients were enrolled, 16 in each group. In the intent to treat analysis 11 (69%) patients in the ofloxacin group and eight (50%) in the imipenem-cilastatin group were cured (p = 0.473; 95% confidence interval of the difference from -14.7% to 52.2%). In the per protocol analysis 10 (91%) patients in the ofloxacin group and seven (70%) in the imipenem/cilastatin group were cured (p = 0.311; 95% confidence interval of the difference from -12.2% to 54%). Our trial suggests that oral ofloxacin is as effective as parenteral therapy with betalactam antibiotics in the treatment of osteomyelitis, which could allow a reduction of the period of hospitalization and economic costs.

CD007775

It is not possible to conclude about the use of any kind of pharmacologic therapies for maintenance treatment of opium dependence.

Twelve-month maintenance treatment of opium-dependent patients.

The goal of this study was to compare the effects of 1, 3 and 8 mg per day doses of buprenorphine in the maintenance treatment of opium-dependent subjects in Iran over a treatment period of 12 months. Participants were randomized to three equal groups (171 subjects per group) of opium-dependent individuals who met the DSM-IV criteria for opioid dependence and were seeking treatment. They were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Overall, 282 subjects (55%) completed the 12 months study. Completion rates by dosage group were 46 (26.9%) for the 1 mg dose group, 102 (59.6%) for the 3 mg dose group, and 134 (78.4%) for the 8 mg dose group (p =.000). These findings are consistent with previous reports of effective buprenorphine use in western countries as a suitable maintenance treatment for opium dependence.

CD007775

It is not possible to conclude about the use of any kind of pharmacologic therapies for maintenance treatment of opium dependence.

Baclofen for maintenance treatment of opioid dependence: a randomized double-blind placebo-controlled clinical trial [ISRCTN32121581].

Results of preclinical studies suggest that the GABA(B) receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. The results support further study of baclofen in the maintenance treatment of opioid dependence.

CD005485

This review identified one small study at moderate to high risk of bias which provided no evidence to inform practice. More research is needed.

Randomised controlled trial of two pressure-relieving systems.

The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.

CD005515

There is weak evidence that the interventions FR-4 with lip-seal training and palatal crib associated with high-pull chincup are able to correct anterior open bite. Given that the trials included have potential bias, these results must be viewed with caution. Recommendations for clinical practice cannot be made based only on the results of these trials. More randomised controlled trials are needed to elucidate the interventions for treating anterior open bite.

Anterior open bite treatment with magnets.

The aim of this study was to examine the effects of repelling magnets on the treatment of anterior open bite and compare them with the effects of acrylic posterior bite-blocks. Twenty patients, aged 9-16 years with skeletal anterior open bite, were randomly divided into two groups. In one group the patients wore posterior repelling magnet splints and in the other they wore acrylic posterior bite-blocks of the same thickness as the magnet splints. The patients were instructed to use their appliance as much as possible (the minimum accepted being 18 hours daily) during a 6-month period. Dental casts, intra-oral photos, and lateral cephalograms were taken before and after treatment, and the patients were also examined regularly to identify the development of any craniomandibular disorders. In the first group, the dental and skeletal vertical relation responded quickly to the magnet treatment. The open bite was generally closed in just under 4 months, especially in patients in early mixed dentition. Spacing in the labial segments decreased in some cases, while slight crowding was induced in others. Transverse problems, i.e. unilateral cross-bite, sometimes followed by scissor-bite on the opposite side, was observed in those patients who were in the early mixed dentition and had used the magnets intensively. The patients who wore acrylic posterior bite-blocks also showed improvement in the dental and skeletal vertical relationships, especially during the first months. This was followed by a 'plateau' period. No transverse problems were found in these patients.

CD005515

There is weak evidence that the interventions FR-4 with lip-seal training and palatal crib associated with high-pull chincup are able to correct anterior open bite. Given that the trials included have potential bias, these results must be viewed with caution. Recommendations for clinical practice cannot be made based only on the results of these trials. More randomised controlled trials are needed to elucidate the interventions for treating anterior open bite.

The effects of Frankel's function regulator (FR-4) therapy on the treatment of Angle Class I skeletal anterior open bite malocclusion.

The present study attempts to evaluate cephalometrically the effects of Fränkel's function regulator (FR-4) appliance on the treatment of Angle Class I skeletal anterior open bite malocclusion. Forty Turkish children (26 girls and 14 boys), with Angle Class I skeletal anterior open bite, were randomly divided into two groups of 20 (13 girls and 7 boys). Patients who had not undergone treatment served as the control group, whereas a second group was treated with lip-seal training and the FR-4 appliance. Chronologic mean decimal age at initial period of the investigation was 8.7 years in the treated group, and 8.9 years in the control group. Treatment and observation periods were 2 years. Investigation was carried out on lateral cephalograms taken before and after the study period. The results indicate that a spontaneous downward and backward growth direction of the mandible observed in the control group could be changed to a upward and forward direction by FR-4 therapy. The skeletal anterior open bite was successfully corrected through upward and forward mandibular rotation.

CD003317

Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture.

The effectiveness of acupuncture in acute stroke remains largely untested and unproved. A randomized, controlled trial was carried out to study the feasibility of acupuncture in combination with conventional supportive treatment for acute stroke patients. A total of 30 patients, aged 46-74, with the onset of symptoms within 36 h were enrolled into the study after appropriate screening. All patients gave informed consent. Basing on the same supportive treatment, patients were randomly assigned to a treatment with or without acupuncture. The procedure and acupoint selection were discussed and decided through several meetings of a group of senior acupuncture doctors in Taiwan. Acupuncture was applied 3 times/week for 4 weeks. During the study period, there were no problems in conducting this trial in terms of patient availability and acceptance, and physician cooperation. A significantly better neurologic outcome was observed in the acupuncture group on day 28 and day 90. The improvement in neurologic status was greatest in patients with a poor neurologic score at baseline. There were no important side effects except for one episode of dizziness related to acupuncture treatment. The data and results of this study will be used as a guideline for planning a full-scale clinical trial, e.g. sample size calculation, method of randomization with stratification of prognostic factors, choosing acupuncture points and technique of acupuncture.

CD003317

Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Can sensory stimulation improve the functional outcome in stroke patients?

After obtaining informed consent, we randomized 78 patients with severe hemiparesis of the left or right side within 10 days of stroke onset: 40 to a control group receiving daily physiotherapy and occupational therapy, and 38 to a group that, in addition, we treated with sensory stimulation (acupuncture) twice a week for 10 weeks. The median age was 76 years for both groups. Motor function, balance, and ADL (Barthel's Index) were assessed before the start of treatment and at 1 and 3 months after stroke onset; ADL was also assessed after 12 months. We assessed the quality of life (QL) using the Nottingham Health Profile 3, 6, and 12 months after stroke onset. Patients given sensory stimulation recovered faster and to a larger extent than the controls, with a significant difference for balance, mobility, ADL, QL, and days spent at hospitals/nursing homes. Whether acupuncture per se is responsible for the differences requires further study.

CD003317

Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Effects of acupuncture treatment on daily life activities and quality of life: a controlled, prospective, and randomized study of acute stroke patients.

BACKGROUND and A number of studies have indicated that acupuncture might improve the functional recovery of stroke patients. These studies vary in inclusion criteria, sample size, and evaluation methods. The present study was designed to investigate whether electroacupuncture treatment favorably affects stroke patients' ability to perform daily life activities, their health-related quality of life, and their use of health care and social services. One hundred four consecutive patients >40 years of age admitted to hospital because of an acute stroke were randomized to 3 groups: deep, superficial, and no acupuncture treatment. The acupuncture treatment given by 4 physiotherapists started 4 to 10 days after randomization and was given twice a week for 10 weeks. All patients underwent conventional stroke rehabilitation as well. Two occupational therapists, blinded regarding the patients' allocation, evaluated the treatment effects. The assessments were performed 4 times during the first year after randomization by means of interviews and observations. There were no differences between the groups with reference to changes in the neurological score and the Barthel and Sunnaas activities of daily living index scores after 3 and 12 months. Regarding the Nottingham Health Profile, the no acupuncture group had somewhat fewer mobility problems. No differences in health care and social services were found between the groups. The present study does not give support to the previous studies, which indicates that acupuncture treatment may have a beneficial effect on acute stroke patients' ability to perform daily life activities, their health-related quality of life, and their use of health care and social services.