Prolonged tracheal intubation in the trauma patient. Recursive cumulative meta-analysis: a diagnostic for the evolution of total randomized evidence from group and individual patient data. Tracheostomy in ventilator dependent trauma patients: a prospective, randomized intention-to-treat study. Difference in patient's acceptance of early versus late initiation of psychosocial support in breast cancer. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. Cabergoline reduces the early onset of ovarian hyperstimulation syndrome: a prospective randomized study. Randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years' corrected age. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study. Feeding premature infants while low umbilical artery catheters are in place: a prospective, randomized trial. Health-related quality of life outcomes in disease-free survivors of mid-low rectal cancer after curative surgery.
Over a 15-month period, 74 trauma patients who were expected to require extended intubation were studied prospectively to evaluate the appropriateness of tracheostomy. Patients were randomized to receive either early (34) or late (40) tracheostomies. The patients also were grouped to determine the difference of early versus late tracheostomy on the development of laryngotracheal pathology and respiratory infections; length of intubation and type of patient injury were studied as possible differential factors. Fifteen per cent (11/74) of the patients developed major laryngotracheal pathology as identified by endoscopy, and respiratory infections developed in 54% (40/74), but there was no significant difference in the complication incidence between the early and late tracheostomy groups. Significantly more complications occurred in rigid-posture, head-injured patients than in any other trauma grouping, but there was no significant difference in the complication incidence between the two tracheostomy groups within that classification. We conclude that patients can undergo translaryngeal intubation for up to 2 weeks without significantly increasing complications relative to transtracheal intubation. Meta-analyses of randomized evidence may include published, unpublished, and updated data in an ongoing estimation process that continuously accommodates more data. Synthesis may be performed either with group data or with meta-analysis of individual patient data (MIPD). Although MIPD with updated data is considered the gold standard of evidence, there is a need for a careful study of the impact different sources of data have on a meta-analysis and of the change in the treatment effect estimates over sequential information steps. Unpublished data and late-appearing data may be different from early-appearing data. Updated information after the end of the main study follow-up may be affected by cross-overs, missing information, and unblinding. The estimated treatment effect may thus depend on the completeness and updating of the available evidence. To address these issues, we present recursive cumulative meta-analysis (RCM) as an extension of cumulative metaanalysis. Recursive cumulative meta-analysis is based on the principle of recalculating the results of a cumulative meta-analysis with each new or updated piece of information and focuses on the evolution of the treatment effect as a more complete and updated picture of the evidence becomes available. An examination of the perturbations of the cumulative treatment effect over sequential information steps may signal the presence of bias or heterogeneity in a meta-analysis. Recursive cumulative meta-analysis may suggest whether there is a true underlying treatment effect to which the meta-analysis is converging and how treatment effects are sequentially altered by new or modified evidence. The method is illustrated with an example from the conduct of an MIPD on acyclovir in human immunodeficiency virus infection. The relative strengths and limitations of both metaanalysis of group data and MIPD are discussed through the RCM perspective. Tracheostomy is a commonly performed procedure in ventilator dependent patients. Many critical care practitioners believe that performing a tracheostomy early in the postinjury period decreases the length of ventilator dependence as well as having other benefits such as better patient tolerance and lower respiratory dead space. We conducted a randomized, prospective, single institution study comparing the length ventilator dependence in critically ill multiple trauma patients who were randomized to two different strategies for performance of a tracheostomy. We hypothesized that earlier tracheostomy would reduce the number of days of mechanical ventilation, frequency of pneumonia and length of intensive care unit (ICU) stay.
                Patients were eligible if they were older than 15 years and either a Glasgow Coma Score (GCS) >4 with a negative brain computed tomography (CT) (no anatomic head injury), or a GCS >9 with a positive head CT (known anatomic head injury). Patients who required tracheostomy for facial/neck injuries were excluded. Patients were randomized to an intention to treat strategy of tracheostomy placement before day 8 or after day 28.
                The study was halted after the first interim analysis. There were 60 enrolled patients, who had comparable demographics between groups. There was no significant difference between groups in any outcome variable including length of ventilator support, pneumonia rate, or death.
                A strategy of tracheostomy before day 8 postinjury in this group of trauma patients did not reduce the number of days of mechanical ventilation, frequency of pneumonia or ICU length of stay as compared with the group with a tracheostomy strategy involving the procedure at 28 days postinjury or more. The present study was performed to assess the difference in acceptance of psychosocial counseling and resulting benefits between patients with breast cancer with early or late onset. In a prospective randomized controlled study conducted over 6 months, 41 women with a new diagnosis of early breast cancer (group 1) and 43 patients with advanced breast cancer (group 2) received individually tailored psychosocial support and were compared against controls. This therapy was free of charge, and the duration of support was determined by the patients' wishes and needs. Among the patients with new onset of disease acceptance of the psychosocial counseling was high, and these patients experienced significant improvements in their quality of life. In contrast, acceptance of psychosocial counseling was low in the advanced breast cancer group and the therapy did not improve quality of life over the observation period of 6 months. Early psychosocial support in patients with breast cancer meets with a high acceptance rate and improves quality of life. To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial.
                Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions.
                There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03).
                There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.
                Copyright 2010 Mosby, Inc. All rights reserved. Prophylactic use of cabergoline has been associated with a decrease in the severity of ovarian hyperstimulation syndrome (OHSS). A prospective randomized study was designed to evaluate the potential of cabergoline to decrease the incidence of OHSS in high-risk patients undergoing assisted reproductive technology treatment; 166 patients with oestradiol concentrations over 4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration were evaluated. They all received 20 g routine preventive intravenous human albumin on the day of oocyte retrieval. They were then randomized into two groups: group A (n = 83) received 0.5 mg oral cabergoline per day for 3 weeks beginning on the day after oocyte retrieval, and group B (n = 83) received no medication. 'Early' OHSS was defined as being when the onset of the syndrome was initiated during the first 9 days after HCG administration, and 'late' OHSS was defined as being when the onset of the syndrome was initiated from 10 days after HCG administration. In group A, no patients progressed to 'early' OHSS and nine patients (10.8%) developed 'late' OHSS; in group B, 12 patients (15.0%) progressed to 'early' OHSS and three (3.8%) to 'late' OHSS. Although the risk of 'early' OHSS decreased significantly (P < 0.001), the risk of 'late' onset OHSS did not. The two groups presented no changes in pregnancy, implantation or miscarriages rates. Iron deficiency in early childhood may impair neurodevelopment. In a masked, randomized, controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of <1301 g, early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions.
                We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants.
                Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry.
                Of the 204 infants initially randomized, 10 died and 30 were lost to follow-up. A total of 164 (85% of the survivors) were evaluated at a median corrected age of 5.3 years. In this population (n = 164), the mean (+/-SD) mental processing composite in the early iron group was 92 (+/-17) versus 89 (+/-16) in the late iron group. An abnormal neurologic examination was found in 17 of 90 versus 26 of 74, and a Gross Motor Function Classification Scale score of >1 was found in 2 of 90 versus 5 of 74, respectively. Fifty-nine of 90 children in the early iron group were without disability, compared with 40 of 74 in the late iron group. Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling, respectively.
                Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect. Because the initial study was not designed to evaluate effects on neurocognitive development, the power was insufficient to detect small but potentially clinically relevant improvements. Additional studies are required to confirm the trend towards a better outcome observed in the early iron group. This study investigated the efficacy of oral melatonin in alleviating jet lag in flight crew after a series of international flights. The optimal time for taking melatonin in this group was also investigated. In a double-blind placebo-controlled trial, 52 international cabin crew were randomly assigned to three groups; early melatonin (5 mg started 3 days prior to arrival until 5 days after return home); late melatonin (placebo for 3 days then 5 mg melatonin for 5 days); and placebo. Daily ratings showed a trend in jet lag, mood, and sleepiness measures toward an improved recovery in the late melatonin group and a worse recovery in the early melatonin group as compared to placebo. Retrospective ratings made 6 days after arrival showed the late melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness than the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin may have potential benefits for international aircrew. Few placebo-controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo-controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients.
                Nineteen patients with a history of birch-pollen-induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment.
                All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty-four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group.
                Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti-inflammatory effect of the treatment. The objective of this prospective, randomized clinical trial was to test the hypothesis that there is no difference in the frequency of feeding problems and necrotizing enterocolitis between a group of premature infants who received early enteral feedings while low umbilical artery catheters (LUACs) were in place, and a late group who were not fed until 24 hours after removal of LUACs.
                Twenty-nine premature infants (born at 28.5 +/- 3.0 SD weeks of gestational age) who were in stable condition received early enteral feedings at a median of 2 days while a LUAC was in place; 31 infants (born at 28.6 +/- 2.7 SD weeks of gestational age) received late enteral feedings at a median of 5 days of age, 24 hours after the removal of the LUAC. Feeding complications and interventions and nutritional characteristics were recorded prospectively.
                There were no differences in the baseline perinatal characteristics of the two groups. The incidence of gastric residua and the incidence of abdominal distention were the same in both groups. The early feeding group had significantly fewer percutaneous central venous catheters, evaluations for sepsis, and episodes of receiving nothing by mouth while a gastric suction tube was in place. Infants in the early group received parenteral alimentation-lipid emulsion infusions for a median of 13 days versus 30 days for the late-fed group (p = 0.0028 by Wilcoxon test). There were two cases of necrotizing enterocolitis in the early group versus four cases in the late group.
                Premature infants in stable condition who receive enteral feedings while LUACs are in place do not have an increased incidence of feeding problems compared with infants who do not receive enteral feedings until 24 hours after removal of LUACs. The main objective of this study was to investigate health-related quality of life (HRQOL) in terms of symptoms and functional outcomes in disease-free survivors of rectal cancer.
                Consecutive patients (n = 117) who underwent curative surgery for rectal cancer with a minimum of 2 years' follow-up and whose disease had not recurred were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and its colorectal cancer module (QLQ-CR38). Long-term HRQOL outcomes were compared with reference data from the general population. Relevant clinical data including type of surgery, stage of disease, type of treatment, and early and late complications were collected. Univariate and multivariate regression analyses were performed to investigate associations among covariates.
                HRQOL functional aspects were similar with that of an age- and sex-matched general population. Although clinically meaningful better outcomes favoring our patients were found for the global health status/HRQOL and the pain scales, constipation was worse in rectal cancer survivors than the general population. Multivariate analysis found that worse physical functioning was associated with increasing age (P < .001), female sex (P < .01), presence of stoma (P < .05), and occurrence of late major complications (P < .05). Worse body image was associated with the presence of stoma (P < .001) and chemoradiotherapy (P < .05).
                Overall, patients with rectal cancer recover well in the long run, with HRQOL levels comparable to that of the general population. HRQOL outcomes provide valuable data that may be used to improve information disclosure to patients.
Updated evidence is of low quality, and potential differences between early and late tracheostomy need to be better investigated by means of randomized controlled trials. At present there is no specific information about any subgroup or individual characteristics potentially associated with better outcomes with either early or late tracheostomy.