As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice.This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for ≥5 patients within 3 months. Patients 6–65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting β-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy.A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29  and for unsuccessful treatment was 1.92 .Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable. Much of the costs of asthma are associated with suboptimally controlled disease -6. By onEach type of inhaler device has its advantages and disadvantages together with cost , and eacPrescription cost-containment measures are increasing in many countries and, as more devices become available, there may be pressure to switch patients to a cheaper inhaler device . Indeed,The purpose of this retrospective database analysis was to evaluate the impact on asthma control of inhaler device switching without an accompanying consultation in general practice in the United Kingdom (UK). Our hypothesis was that, for patients with asthma, switching inhaler device without a consultation is associated with worsened clinical outcomes.This 2-year retrospective matched cohort study included a baseline period of 1 year before the date of ICS device switch (index date) and an outcome period of 1 year after the index date. Patient data were drawn from 1990–2004 records in the General Practice Research Database (GPRD), a large computerized database of anonymized longitudinal medical records from primary care in the Uk . The yeaPatients eligible for inclusion in this analysis were receiving ICS, were 6–65 years of age on the index date, and had a recorded diagnosis of asthma and no record of chronic obstructive pulmonary disease (COPD). We used the GPRD to identify primary care practices where ICS inhaler devices were switched without an accompanying consultation on the same day for five or more patients within a 3-month period. Patients had to be registered at the practice for at least 1 year before and 1 year after the index date. We included switches to inhaler devices that require training to use, namely, from a dry powder inhaler to a metered-dose inhaler, another brand of dry powder inhaler, or a breath-actuated inhaler or from a breath-actuated to a metered-dose inhaler or another brand of breath-actuated inhaler. Patients changed to a device recorded as 'generic' were excluded.Each patient included in the analysis was individually matched to another patient (from any practice) who was receiving the same ICS device on the index date and met the following six criteria: same sex, age within 5 years, same smoking status, match on presence or absence of rhinitis history, and, during the prior year, same number of oral corticosteroid prescriptions and hospitalizations for asthma.Outcome measures were analyzed for the year before (baseline period or year 1) and the year after the index date (outcome period or year 2). The primary outcome measure was a composite measure of asthma control, as defined in Table Other data recorded for each patient included assigned socioeconomic status of the primary care practice and other respiratory or confounding diagnoses. The daily dose of ICS was calculated from the prescribing instructions on the first available prescription after the index date.t and χ2 tests as appropriate. Median intended ICS dose, daily short-acting β-agonist dose, and asthma consultation pattern during the baseline year were compared for the two cohorts using the Mann-Whitney U test. For comparison of change between year 1 and year 2, the paired t test (mean changes in short-acting β-agonist use and asthma consultations) and χ2 test (change or not in ICS dose or device from year 1 to year 2) were used.Baseline characteristics of switched and matched control patients were compared using For comparisons of the primary outcome measure, in addition to the unadjusted analyses, we used logistic regression to correct for potential baseline confounders. Binary regression models were constructed using as the three outcome variables 1) successful vs. partially successful/unsuccessful treatment, 2) unsuccessful treatment vs. successful/partially successful treatment, and 3) subsequent change in ICS device or dose and, as explanatory variables, cohort membership plus possible confounding factors. Possible baseline confounders entered into the model included 1) short-acting β-agonist use ; 2) asthma consultation rate ; 3) socioeconomic status (in quintiles); and 4) prescribed ICS dose at switch .We identified 112,090 patients with asthma in the GPRD database who had a switch of ICS device  and long acting beta agonists are two possible sub-group analyses. However, care would need to be taken not to decrease the size of the cohort such that the power of the study becomes too weak to make conclusions from the findings.In conclusion, switching of ICS inhaler devices without a consultation is most commonly used for substitution of a cheaper metered-dose inhaler in place of a dry powder inhaler. Switching ICS inhaler devices without a consultation was associated with worsened asthma control. Therefore, the possible costs of adverse effects on asthma control should be weighed against savings in acquisition costs before instituting mass switching of ICS inhaler devices. Switching ICS inhaler devices without a face-to-face evaluation and consultation is inadvisable.CI: confidence interval; COPD: chronic obstructive pulmonary disease; GPRD: General Practice Research Database; ICS: inhaled corticosteroid; IQR: interquartile range; OR: odds ratio; SABA: short-acting β-agonist; UK: United Kingdom.MT has received speaker honoraria from GlaxoSmithKline, Merck Sharp & Dohme, and Teva Pharmaceutical Industries and advisory panel honoraria from GlaxoSmithKline, Merck Sharp & Dohme, Teva, and Schering-Plough. He has received grants and research support for research in asthma from Asthma UK, GlaxoSmithKline, Merck Sharp & Dohme, and AstraZeneca.DP has consultant arrangements with Altana Pharma, GlaxoSmithKline, and Ivax. He or his team have received grants and research support for research in asthma from the following organizations: UK National Health Service, Altana Pharma, AstraZeneca, GlaxoSmithKline, Ivax, Merck Sharpe & Dohme, Novartis, and Schering-Plough. He has spoken for Altana Pharma, GlaxoSmithKline, and Merck Sharpe & Dohme.HC was at the School of Pharmacy, University of Bradford, Bradford, UK, at the time of this study. Prof. Chrystyn has been consultant to and received grants to attend conferences from the pharmaceutical industry, and he has received research grants and equipment from the pharmaceutical industry for his research group. The pharmaceutical companies are Aerogen, Altana Pharma, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Innovata Biomed, Meda Pharmaceuticals, Merck Sharp & Dohme, Omron, Orion, Ranbaxy, TEVA UK and Trinity-Chiesi. He has no personal shares with any pharmaceutical company.AL, at the time of this study, worked for United BioSource Corporation (UBC) who were paid by GlaxoSmithKline for his time in this research project. UBC have worked with all of the major pharmaceutical companies to provide consultancy services. He has no personal shares and has never received any personal fees from any pharmaceutical company.AW was an employee of GlaxoSmithKline R&D when this work was undertaken.JZi is an employee of Respiratory Research, Ltd.MT, DP, HC, AL and AW all contributed to the conception, design and interpretation of the analysis of the study. MT, DP and JZ led the analysis of the dataset. All authors have been involved in the drafting of the manuscript and have given final approval of the version to be published.The pre-publication history for this paper can be accessed here:


High levels of rural to urban migration are a feature of most African countries. Our aim was to investigate changes, and their determinants, in cardiovascular risk factors on rural to urban migration in Tanzania.Men and women (15 to 59 years) intending to migrate from Morogoro rural region to Dar es Salaam for at least 6 months were identified. Measurements were made at least one week but no more than one month prior to migration, and 1 to 3 monthly after migration. Outcome measures included body mass index, blood pressure, fasting lipids, and self reported physical activity and diet.-1 respectively, p < 0.001); and in men, not women, total cholesterol increased , and triglycerides fell . Blood pressure appeared to fall in both men and women. For example, in men systolic blood pressure fell by 5.4 mmHg, p = 0.007, and in women by 8.6 mmHg, p = 0.001.One hundred and three men, 106 women, mean age 29 years, were recruited and 132 (63.2%) followed to 12 months. All the figures presented here refer to the difference between baseline and 12 months in these 132 individuals. Vigorous physical activity declined , and weight increased . Intake of red meat increased, but so did the intake of fresh fruit and vegetables. HDL cholesterol increased in men and women (0.24, 0.25 mmollThe lower level of physical activity and increasing weight will increase the risk of diabetes and cardiovascular disease. However, changes in diet were mixed, and may have contributed to mixed changes in lipid profiles and a lack of rise in blood pressure. A better understanding of the changes occurring on rural to urban migration is needed to guide preventive measures. Since 2008, and for the first time in human history, over 50% of the world's population lives in urban areas. In sub In low and middle income countries, urban compared to rural living is strongly associated with a higher prevalence of certain chronic, non-communicable, conditions, including hypertension, glucose intolerance, obesity and dyslipidaemia,4. WithiDespite these well known rural to urban differences there are scant data on the speed, size and determinants of changes that occur on rural to urban migration in regions such as sub Saharan Africa. Our overall goal in establishing the Urbanization and Metabolic Outcomes Study in Tanzania (UMOST) was to determine if changes in blood pressure and lipids occurred within the first twelve months of rural to urban migration, and if so what determinants underlay those changes. The first phase of this study, on which this report is based, was designed to estimate the direction, size and variance of any changes, and help to generate hypotheses on the determinants of those changes. In a preliminary short report from this study, using data from two time points, baseline and 6 months, we described changes in a number of biological variables over the first six months following rural to urban migration. We foun1. Following migration there is a marked decline in physical activity, and this partly accounts for increasing body mass index2. Following migration there is increased consumption of fresh fruit, vegetables and meat, and these dietary changes partly account for changes in blood pressure and lipids.3. Increasing body mass index will be related to increasing blood pressure and triglycerides, such that over time any beneficial changes seen in the few months following migration in these factors will start to be reversed.In this paper we describe changes in the migrants over 12 months, including data on changes in behaviours, such as physical activity and aspects of diet. We examine putative determinants of changes in the biological variables, guided by the above hypotheses, making use of all available data collected at baseline and nine time points following migration.This was a cohort study of rural to urban migrants. It was based in Morogoro rural district, 200 km west of the city of Dar es Salaam, and within Dar es Salaam. The study took advantage of the infrastructure established for a demographic surveillance system, the Adult Morbidity and Mortality Project,12. ThroHeight was measured using a Leicester Stadiometer to the nearest half centimetre, and weight measured to the nearest kilogram, without shoes and wearing light clothes, on a seca scale. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Waist circumference was measured twice using a dress makers tape to the nearest centimetre in the mid-axillary line at the mid point between the lower costal margin and the iliac crest, in gentle expiration with the feet shoulder width apart; the mean of the two measurements was used in analysis. Blood pressure (BP) was measured twice in the right arm with an automated machine (Omron M4), using an alternate size cuff, with the participant seated, after 5 minutes rest and with 5 minutes between measurements. The mean of the two measurements was used in analysis. Fasting blood was taken for plasma lipids, which included total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides. These were measured throughout the study in same laboratory at Muhimbili University of Health and Allied Sciences on a Cobas Mira Plus analyser using reagents supplied by the manufacturer. Low density lipoprotein (LDL) cholesterol was estimated using the Friedewald formula. Data coData on behaviours were collected by interview using questionnaires specifically developed and previously used within Tanzania by the investigators,15. DataData collected on social and economic circumstances included years of education at primary, secondary and tertiary levels, current main occupation, presence or absence of electricity supply to their residence and source of water supply.Changes between baseline and 12 months are summarised as means or proportions, differences presented with 95% confidence intervals and statistical significance assessed using the paired T test for continuous variables and McNemar's test for discrete variables. A p value of < 0.05 was considered statistically significant. These analyses of change were performed in the individuals who completed 12 months follow up i.e. had data at baseline and at 12 months.2 Statistics. All analyses were undertaken using the package SAS [Mixed linear models with a random intercept were usekage SAS . Two mai-2 , mean systolic blood pressure 124.4 vs 125.9 mmHg , and mean cholesterol 4.1 vs 4.2 mmoll-1  respectively.Table The majority of migrants, 69% (95% CIs 63 to 76%), reported their religion as Muslim Table , with thTwelve months following migration, 42% (33 to 50%) still described their main occupation as farming, 19% (12 to 26%) as business, 15% (9 to 21%) as being in education (as a student), and among the 64 women, 20% (10 to 30%) as being a housewife or house girl. Fifty five percent (47 to 64%) of migrants lived in households supplied with electricity and water was available from a household or neighbour's tap for 92% (88 to 97%).In both men and women physical activity decreased markedly following migration Table , with thThe diet scores Table  represenThe changes in biological variables between baseline and 12 months are shown in Table -2 and waist by 2.18 (1.05 to 3.31) cm. Figure Weight, body mass index and waist circumference increased in both men and women Table  e.g. in In both men and women there were falls in systolic and diastolic blood pressure, from a fall in systolic BP in men of -5.4 ( -9.3 to -1.6) mmHg to -8.6 (-13.7 to -3.4) in systolic BP in women. Figure As part of exploring the possibility that the fall in blood pressure represented habituation i.e. becoming used to having blood pressure measured, the difference between the first and second blood measurement on each occasion was examined. At baseline the mean difference between the first and second systolic blood pressure measurement in the 132 participants followed up to 12 months was 4.6 (2.5 to 6.8) mmHg, and for diastolic blood pressure it was 1.8 (0.6 to 3.0) mmHg. At 12 months the differences were 0.4 (-1.7 to 2.5) mmHg and 1.5 (-0.1 to 3.1) mmHg respectively. One interpretation of these findings is that at baseline the first blood pressure measurement is strongly influenced by the lack of familiarity with the procedure, particularly for systolic blood pressure. Given this, the change in blood pressure between baseline and 12 months was also examined using the second reading only (rather than the mean of the first and the second).When only the second blood pressure reading is used the difference between baseline and 12 months in men was -8.1 (-5.2 to -11.1) mmHg for diastolic blood pressure, and -3.9 (0.6 to -8.3) mmHg for systolic blood pressure; with equivalent values in women of -7.6 (-3.7 to -11.4) mmHg, and -5.9 (-0.3 to -11.4). Thus, using only the second reading the findings were qualitatively similar, but with a smaller, and in men non-significant, fall in systolic blood pressure. In addition, the second reading at baseline was compared with the first reading at 12 months, and the findings were little different.The change in blood pressure was also examined after excluding those who reported a diagnosis of hypertension and taking blood pressure lowering medication. There were two such individuals at baseline , and 9 individuals  at the 12 month follow up. Excluding these individuals from the analysis made little difference to the fall in blood pressure between baseline and 12 months, being for example -5.2 (-9.3 to -1.3) mmHg for systolic blood pressure in men, and -6.6 (-11.5 to -1.7) mmHg for systolic blood pressure in women.Finally, the difference in blood pressure between baseline and 12 month follow up was examined by higher  or lower blood pressure at baseline Table . Those w-1 and 0.25 (0.13 to 0.37) mmoll-1respectively. In women there was little change in total cholesterol and cholesterol to HDL ratio fell , where as in men total cholesterol increased  and there was little change in HDL to cholesterol ratio. Serum triglycerides fell significantly in men at 12 months  but not in women. However, as Figure -1, but reduced to a non-significant difference towards the end of the 12 month follow up.Due to the lack of a fasting sample at either baseline or 12 months, lipid results were missing on 17 men and 18 women Table . In bothTable In this study we set out to investigate changes and their determinants in cardiovascular and diabetes risk factors in the year following rural to urban migration in Tanzania. Following migration we found some changes that would be predicted by published cross sectional data, and others that seem contrary to them. Thus, as expected physical activity decreased markedly, and there was evidence of saturated fat consumption increasing. However, there was also evidence that consumption of fresh fruit and vegetables also increased. As expected, over 12 months following migration weight and waist circumference increased, and total cholesterol significantly increased in men, but did not in women. Contrary to expectation, HDL cholesterol increased in both men and women, and in women the ratio of total to HDL cholesterol fell. In men, but not women, there was a significant fall in triglycerides over 12 months. Blood pressure fell in both men and women.Before attempting to appraise the importance of the findings from this study, it is crucial to acknowledge its strengths and limitations. Strengths of this study include the fact that participants were recruited, with measures made, prior to migration, and that a reasonable proportion (63%), particularly for the challenging nature of the urban environment, were followed to the end of the study. There were not systematic differences at baseline between those lost to follow up and those not. The inclusion of lipids, the first migration study as far as we are aware to have done so in sub Saharan Africa, is also a strength. The lipids at baseline were transported on the same day from the rural area to the laboratory in the urban area, a two to three hour bus journey, and realistically half a day from taking the sample to separating and analysing the sample in the laboratory. However, cholesterol and triglycerides are highly stable analytes, even after, for example, with the sample being left for at least 24 hours at 35 degrees centigrade. LimitatDespite the obvious limitations we believe that this study provides important and novel insights. Blood pressure did not rise following migration. The fall in blood pressure was unexpected. It was not explained by treatment of hypertension following migration, occurred in both those with higher and lower blood pressure at baseline, and was apparent whether the mean of the blood pressure readings taken on each occasion was used or only the second reading. Nonetheless, it seems likely that much of the fall we found in blood pressure is the result of habituation, with increasing familiarity and less anxiety on repeated measures. A previous study in residents (not migrants) of Dar es Salaam evaluateAs described above, we found mixed changes in lipid levels. A plausible explanation for these changes are changes in diet, with ouIn contrast to the perception of urban living in low and middle income countries being universally detrimental for cardiovascular risk, the findings from this study suggest that a more nuanced understanding may be appropriate, at least in some settings. Urban compared to rural living may offer some advantages, including access to a more varied diet, but this is against a background of lower levels of physical activity and rising overweight and obesity. A better understanding of how risk changes on migration is central to considering measures to prevent the rising levels of diabetes and cardiovascular disease in low and middle income countries.The authors declare that they have no competing interests.NU was involved in the design and management the study throughout, and led the writing of the paper; PJ assisted with data management, carried out all the statistical analyses and drafted relevant sections of the paper; DM was the project manager in Tanzania and coordinated all aspects of the data collection and data entry; HM was the principal investigator in Morogoro, and contributed to the detailed study protocol and greatly facilitated its local implementation; PN and MN both contributed to the development of the detailed study protocol and oversaw its implementation in Morogoro; BT contributed to the development of the detailed study protocol and in particular oversaw the biochemical assays at Muhimbili National Hospital; RM provided detailed input into the design, execution and interpretation of the statistical analyses. All authors approved the submitted version of the paper.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/272/prepub


Global Initiative Strategy for Asthma Management (GINA) is poorly applied in undeveloped and developing countries. The current study examined the effects of applying GINA guidelines on treatment efficacy in asthmatic patients in Iran.Twenty four asthmatic patients  were treated as usual and 26 patients (intervention group) according to the GINA for 2 months. Asthma symptom score, asthma severity, frequency of symptoms/week and wheezing were recorded at the beginning (first visit), one month after treatment (second visit), and at the end of the study (third visit). Pulmonary function tests (PFTs) were performed by spirometry, and the patients' use of asthma drugs and their symptoms were evaluated, at each visit.Asthma symptoms, frequency of symptoms/week, chest wheezing, and PFT values were significantly improved in the intervention group at the second and third visits compared to first visit . In addition, exercise induced cough and wheeze were significant improved in the third visit compared to the second visit in this group (p < 0.01 for both measures). In the second and third visits all symptoms were significantly lower, and PFT values higher, in the intervention group compared to the usual care group (p < 0.005 to p < 0.001). In the usual care group, there were only small improvements in some parameters in just the second visit . The use of asthma drugs was unchanged in the usual care group and significantly reduced in the intervention group (p < 0.01) by the end of the study.Adoption of GINA guidelines improves asthma symptoms and pulmonary function in asthmatic patients in Iran. Asthma is known as a chronic disease, and epidemiological studies indicate that its prevalence is increasing worldwide . The reaThere is still debate about how asthma should be treated pharmacologically and at what stage anti-inflammatory therapy should be introduced . Low useThe goals of asthma treatment have been significantly altered in the new guidelines . More atIn the present study, we examined the effect of adopting the Global Initiative Strategy for Asthma Management (GINA) to treat asthma patients in Iran on asthma symptoms (including wheezing) and spirometric measures of pulmonary function.Fifty asthmatic patients were recruited from the Asthma Clinic, Ghaem Medical Centre, Mashhad University of Medical Sciences and divided randomly into a usual care group  and a intervention group . Inclusion criteria were: 1) previously diagnosed with asthma by a physician. 2) Two or more of the following symptoms: recurrent wheeze, cough or chest-tightness at rest; nocturnal or early morning wheeze, cough or chest-tightness; and wheeze or cough during exercise, 3) FEV1 and PEF less than 80% predicted values, 4) No history or symptoms of cardiovascular or other respiratory diseases that required treatment (excluding the common cold). The studied patients had moderate to severe asthma according to GINA guidelines [Each patient was treated for a period of two months and was visited and evaluated three times over this period. The treatment regimen of all patients included inhaled corticosteroid, mostly beclomethasone dipropionate (400–1400 μg depending on disease severity) and in some cases fluticasone dipropionate 500 μg). The treatment regimen included oral corticosteroids in 64% of the patients. Ninety-seven percent of patients received methyl xanthine and 58% received inhaled salbutamol. None of the patients had oral β-agonist drugs as part of their treatment regimen. Very few patients were under an acceptable therapeutic regimen for asthma at the start of the study according to GINA guidelines [00 μg. ThThe intervention group was treated according to the GINA guidelines . They we1), peak expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory flow at 75%, 50% and 25% of the FVC  were taken independently from the three curves.Pulmonary function tests were also measured in the beginning and at the end of the study using a spirometer with a pneumotachograph sensor . Prior to pulmonary function testing, the required manoeuvre was demonstrated by the operator, and subjects were encouraged and supervised throughout test performance. Pulmonary function testing was performed using the acceptability standards outlined by the American Thoracic Society (ATS) with subjects in a standing position and wearing nose clips . All tesBased on the prevalence of asthma in Iran, using the PPS sampling method, it was calculated that a minimum of 15 subjects in each group would be needed to detect a 4% difference with an α error of 1% and a power of 95%. However, 24 patients as usual care and 26 patients as intervention group were studied. The data of asthma symptom score, chest wheeze, and frequency of occurrence of symptoms/week were expressed as mean± SEM and PFT values and those of height and age as mean± SD. All data were compared between the beginnings, middle and the end of the study (three visits) using repeated measure analysis of variance (ANOVA) and between usual care and intervention groups using unpaired "t" test. Due to the time-group interaction of the data, multivariate method (repeated measurements) was not applied for comparison of the beginnings, middle and the end of the study (three visits) between usual care and intervention groups. The difference of percentage of patients using each type of drug between each two visits was tested by Chi-square testing on 2 × 2 contingency tables. Significance was accepted at p < 0.05.All symptom scores of asthmatic patients treated according to GINA guidelines (intervention group) were improved even after 1 month's treatment (second visit) and at the end of the study . In addition, exercise induced cough was significantly improved in the third visit compared to the second visit in this group (p < 0.01), Fig. . HoweverAsthma severity score, frequency of occurrence of asthma symptoms/week and chest wheezing were also control improved at the second and third visit in the intervention group (p < 0.001 for each measure). The symptoms/week continued to control improve significantly between the second and third visits in this group (p < 0.01), Fig. . In the All PFT variables were abnormally low in both groups of patients at the beginning of the study . In the intervention group, all PFT values were significantly higher in the second visit (p < 0.01) and the third visit (p < 0.001) compared to the first Fig . Since PThe use of inhaled and oral β-agonists, inhaled and oral corticosteroid, and oral theophylline was decreased at the end of the study for the intervention group; the proportion of patients employing the correct technique when using their inhaler increased from 31% (visit 1) to 100% (visit 3) in this group. No obvious changes noted for the usual care group with regard to drug use or proportion of patients employing the correct technique when using their inhaler table . In TablThe results of the present study showed greater improvement in asthma symptoms and in pulmonary function of patients treated according to GINA guidelines comparing to a usual care group receiving usual treatment.According to the guidelines the main aims of asthma management are to control symptoms maintain pulmonary function close to a normal level and maintain normal physical activity levels . In the At the start of the study, the PFT values, symptoms score, asthma severity and chest wheeze tended to be worse in the usual care group compared to the intervention group, though these differences did not achieve statistical significance. This tendency may have reflected a slightly more severe level of disease and a greater expectation of treatment benefit in the usual care group. Thus, the short term improvement noted in the usual care group at the second visit, which were smaller in magnitude to that seen in the intervention group and were reversed by the third visit, were probably a placebo effectGlobal Initiative for Asthma.The score of asthma symptoms used in the present study was based on questionnaires used in our previous studies . The preparation of the questionnaire was described in our previous study (Reference 4). Briefly, a questionnaire in the Farsi language was designed in accordance with several previous questionnaires and based on the definition of asthma used in the Several previous studies have demonstrated the efficacy of applying various guidelines in the management of asthma. For example it has been shown that the regular measurement of PEF can lead to reduction of drug use in asthmatic patients, specially of bronchodilators and corticosteroids, ,13, reduHowever, in undeveloped and developing countries guidelines are poorly applied. Our previous studies showed that most asthmatic patients in Iran were not well treated and were not able to administer their inhaler drugs correctly ,4,7,9,16Few studies have previously tested the effect of applying guidelines in the management of asthma in countries of our region. Alamoudi  examinedIn addition to this, we have previously shown that most asthmatic patients in Iran did not receive adequate knowledge regarding avoidance of risk factors and of acceptable treatment regimens. The addition of a standard treatment plan in asthmatic patients led to improvement in symptom score and PFT values . We haveThe application of GINA guideline 2002 in treating asthmatic patients showed significant improvement in asthma therapy. Therefore, the application of GINA guideline 2006 my resulted in greater improvement in treating asthmatic patients. In addition, in the present study patients were studied for relatively short period of time (2 months) and treating patients for longer period could lead to better results. However in this study period, there was significant improvement in treatment of patients. This may be due to education and style deficiency in treating asthmatic patient in our country.Although the questionnaire used in the present study was validated in the previous studies ,8,10, thThe present study extends the findings of our previous studies by demonstrating the suitability of adopting GINA guidelines in the management of asthma in countries of our region. The demonstration of significant improvements in asthma symptoms , severity, drug usage, inhalation technique, and PFT values after applying GINA guidelines is promising. However, further studies are needed with greater numbers of patients with a wider range of disease severity. The long term benefits will also need to be tested by monitoring the effects over a longer period.The pre-publication history for this paper can be accessed here:


To investigate the clinical differences between pulse wave velocity and augmentation index in diabetic retinopathy.The subjects were 201 patients with type 2 diabetes. These subjects were measured for both augmentation index (AI) and brachial-ankle pulse wave velocity (baPWV) by a pulse wave analyzer. The relationships between AI, baPWV, and diabetic retinopathy were examined.BaPWV was significantly higher in patients with diabetic retinopathy than in individuals without the disease. (20.13 ± 3.66 vs.17.14 ± 3.60 m/s p < 0.001) AI was higher in patients with diabetic retinopathy, but not significantly. (19.5 ± 15.2 vs. 14.8 ± 20.5% p = 0.14) The association between baPWV and diabetic retinopathy remained statistically significant after adjustment.  On the other hand, the association between AI and diabetic retinopathy was not statistically significant. BaPWV is associated with diabetic retinopathy, but AI is not. The clinical significance appears to be different between PWV and AI in patients with diabetes. Both pulse wave velocity (PWV) and augmentation index (AI) are known as markers of arterial stiffness . These pJapanese patients with type 2 diabetes who had randomly undergone testing for both baPWV and AI of the common carotid artery between April 2002 and April 2003 at the outpatient department of the Juntendo University Hospital  were enrolled in this study. Informed consent was obtained from all subjects. Clinical data were collected in a cross sectional manner from medical records. Type 2 diabetes was indicated by a fasting plasma glucose concentration >7.0 mmol/L without treatment, a plasma glucose concentration 11.0 mmol/L measured 2 h after a 75 g oral glucose load, or by treatment with a glucose-lowering drug. The patients selected for the study were in a state of sinus rhythm. The patients selected for the study had no history of ketoacidosis, ischemic heart disease, peripheral artery disease or ischemic stroke. Patients with an ankle-brachial pressure index (ABI) <0.9 were excluded from the analysis. Diagnoses of diabetic retinopathy were made by ophthalmologists based on the presence of one or more of the following clinical features in the fundus: hemorrhages, hard or soft exudate, venous beading, intra-retinal microvascular abnormalities, cotton-wool spots, pre-retinal new vessels, fibrous proliferation and/or photocoagulation scars. Diabetic nephropathy was defined as a casual urinary albumin/creatinine ratio >30 mg/g Cr. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride and hemoglobin A1c (HbA1c), urinary albumin and creatinine levels were determined using standard laboratory techniques.Measurement of baPWV and AI were performed on the same day. The automatic pulse wave analyzer  was used to measure baPWV, AI and ABI. This device has been approved by the US food and drug administration. The device simultaneously performs an electrocardiogram, phonocardiogram, bilateral brachial and ankle blood pressure (BP), and carotid arterial pulse wave. The detailed method to measure baPWV and ABI was previously reported ,6. BriefCarotid arterial pulse wave were obtained using arterial applanation tonometry incorporating an array of 15 micropiezoresistive transducers. Advanced multiplexing electronics combined with automatic sensor selection relative to the target artery facilitated and ensured optional placement of the sensor. The carotid sensor was manually placed on the common carotid artery. The systolic portion of the central arterial waveform is characterized by two pressure peaks. The first peak is caused by left ventricular ejection, whereas the second peak is a result of wave reflection. The difference between both pressure peaks reflects the degree to which central arterial pressure is augmented by wave reflection. The AI (%) is defined as the percentage of the central pulse pressure which is represented by the reflected pulse wave and, therefore, reflects the degree to which central arterial pressure is augmented by wave reflection . The relIn order to compare the association between baPWV and diabetic retinopathy, and between AI and diabetic retinopathy, we performed several statistical analyses. First, subjects were divided into two groups: those with and those without diabetic retinopathy. Clinical characteristics, including baPWV and AI, were analyzed within the two groups. Continuous variables were presented as the mean standard deviation (S.D.). Continuous variables were compared using Student's t-test and categorical data were compared using the chi-squared test. Second, we used linear regression analysis to investigate the correlation between baPWV and AI. Third, multiple regression analysis was performed to investigate the relationship between arterial stiffness markers and clinical parameters. Multiple logistic-regression analysis was used to provide the adjusted odds ratios (ORs) for baPWV and AI for diabetic retinopathy. The following factors were adjusted for: age, gender, duration of diabetes, HbA1c level, diabetic nephropathy, hypertension (systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg) and hyperlipidemia . In addition, AI was increasing more in younger individuals ,12. TherThe presence of diabetic retinopathy was confirmed in 47 (23.4%) of the 201 patients who were eligible to take part in the study. Table On the multiple regression analysis, age, duration, heart rate, and SBP were dependent determinants of baPWV, while age, height, heart rate, and DBP were independent determinants of AI. table The results of the logistic regression analyses are shown in table In this study, there was a significant positive association between the presence of diabetic retinopathy and baPWV among Japanese type 2 diabetic patients without macroangiopathy. However, the association between AI and diabetic retinopathy was found to be uncertain. The correlation between baPWV and AI was weak. The determining factors were different between baPWV and AI.Previously, we showed baPWV is associated with diabetic retinopathy . PWV is The duration of diabetes determined baPWV, but not AI, in this study. In addition, PWV was increased in patients with diabetes, but this is not associated with AI . In thisAI was correlated with height, heart rate, SBP. On the other hand, baPWV was correlated with age, SBP, and heart rate . In addiInsulin sensitivity reportedly influences AI , but wasA positive association between AI and diabetic retinopathy has been previously reported . In thatPWV and AI are reported markers of arterial stiffness, but differing results have been obtained for diabetic retinopathy. The clinical significance of PWV and AI appears to be different in patients with diabetes.Omron Colin Corporation supported this study by supplying the pulse wave analyzer.OO participated in the design of the study and drafted the manuscript. KH and TW carried out measurements of pulse wave velocity and augmentation index. JK performed statistical analyses. MK and HY contributed to the study design and revised the manuscript. RK participated in the study design and coordination. All authors read and approved the final manuscript.


Due to its important role in the regulation of vascular tone and blood pressure, we aimed to investigate the association between the Arg347Cys polymorphism in the α1A-AR gene and blood pressure phenotypes, in a large sample of Brazilians from an urban population.The alpha1A-adrenergic receptor , but not systolic blood pressure (p = 0.12). In addition, presence of the Cys/Cys genotype was marginally associated with hypertension in our population (p = 0.06). Significant interaction effects were observed between the studied genetic variant, age and physical activity. Presence of the Cys/Cys genotype was associated with hypertension only in individuals with regular physical activity  or younger than 45 years .Physical activity and age may potentially play a role by disclosing the effects of the Cys allele on blood pressure. According to our data it is possible that the Arg347Cys polymorphism can be used as a biomarker to disease risk in a selected group of individuals. Increased blood pressure constitutes a major risk factor for cardiovascular diseases, including kidney and cerebrovascular diseases,2. Altho1A-AR) regulates the cardiac and peripheral vascular system through sympathetic activation. Because of this characteristic, the α1A-AR is considered an important participant in blood pressure homeostasis[1A-AR gene (ADRA1A), located on chromosome 8q21[in vitro[ADRA1A could modulate cardiac or vascular sympathetic tone and might contribute to the pathogenesis of hypertension and cardiovascular disease.The alpha1A-adrenergic receptor  attended the clinic visit and the physical examination emphasized measurement of height, weight, and blood pressure. Major cardiovascular risk factors, such as, obesity phenotypes, ethnicity, smoking status, amount of physical activity, hypertension and metabolic syndrome, were also evaluated. Laboratorial analyses were conduced to evaluate blood glucose, total-cholesterol, lipoprotein fraction, and triglycerides.This study was approved by Ethics Committee for Research on Human Subject of the Universidade Federal do Espírito Santo, and all subjects gave written informed consent to participate.2) was calculated and overweight or obesity defined as BMI ≥ 25 or 30 Kg/m2, respectively. All participants were also submitted to a racial classification according to a validated questionnaire for the Brazilian population[Presence of traditional cardiovascular risk factors was determined using the criteria standardized by The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Weight opulation,15. SubjAccording to the Third Report of the National Cholesterol Education Program criteria, metabolBlood pressure was measured using a standard mercury sphygmomanometer on the left arm after 5 minutes rest, in the sitting position. Systolic and diastolic blood pressures were calculated from three readings, with a minimal interval of 5 minutes and the average value was used in the analysis. Hypertension was defined as mean systolic blood pressure (SBP) of ≥ 130 mmHg and/or diastolic blood pressure (DBP) of ≥ 85 mmHg or the current use of anti-hypertensive medication. This deGenomic DNA was extracted from leukocytes in samples of whole blood, following a standard salting-out technique. Genotypt-test, while χ2 tests were used for categorical variables. Allele and genotype frequencies among the study participants were calculated using the StatView for Windows statistical program (version 5.0). The goodness of fit for normal distribution was evaluated using the Kolmogorov-Smirnov test. Hardy-Weinberg equilibrium for the distribution of the genotypes was estimated by the χ2 test using the StatView program. The effects of ethnicity on blood pressure status and genotype frequencies were analyzed by χ2 tests.Comparisons of continuous variables were performed by Student unpaired t test and ANOVA were used to investigate the association between genotype and the different phenotypes studied. The association between Arg347Cys polymorphism and blood pressure phenotypes was assessed by analysis of odds ratio (OR), respective 95% confidence intervals (CI) and two-tailed p value . Genetic models of action of the studied variants were constructed by combining genotypes .Unpaired Association between a particularly chosen genetic model, common risk factors  and blood pressure phenotype was examined with simple and multiple logistic regressions. These analyses were conduced using the SPSS program (version 12.0).p values < 0.05 on a two-tailed test were considered statistically significant.Quantitative variables were expressed as the mean ± standard deviation, and p > 0.05). Genotypes were differently distributed regarding ethnicity (p < 0.001). This difference was due to a higher frequency of the Cys allele in African-descendent individuals as compared to Caucasian-descendent ones.Table Association analysis indicated a significant difference between genotype groups with respect to diastolic blood pressure and a tendency towards increased systolic blood pressure associated with the presence of the Cys allele using an additive mode of action Table .p = 0.056). After adjustment for gender, age, and ethnicity, presence of the risk allele in homozygosis was not significant .Considering a recessive mode of action for the Cys allele , presence of the Cys/Cys genotype was marginally associated with hypertension in our population . We did not find evidence for an interaction effect between the studied genetic variant and obesity (p = 0.23), smoking status (p = 0.66), total-cholesterol (p = 0.46), LDL-cholesterol (p = 0.74), HDL-cholesterol (p = 0.71), triglycerides (p = 0.84), glucose intolerance (p = 0.84) or metabolic syndrome (p = 0.67).Exploring potential interaction effects between the Arg347Cys polymorphism and other determinants of blood pressure, we have interestingly observed a context-dependent effect of the polymorphism regarding physical activity Figure . In thisp = 0.04). On the contrary, despite a higher prevalence of hypertension in the older individuals sample, there is no clear association between the Cys/Cys genotype and hypertension (p = 0.46).Another way of testing this potentially relevant interaction effect is to study the differential effect on hypertensive status modulated by the Arg347Cys variant comparing populations with different ages. Here, we have hypothesized that individuals of younger age (and conceivably fitter) may show a different effect of the Cys/Cys genotype when compared to the same genotype effect in individuals from a higher age group. In Figure The data presented in this study provide evidence for a discrete association between Arg347Cys polymorphism and blood pressure related phenotypes in the general population studied. Nevertheless, a stronger association between the Cys allele and hypertension was clearly observed in the subpopulations of fitted and young individuals. These findings suggest that the effect of this allele in blood pressure regulation is only evident when taking into account physical fitness. Physical activity, potentially, may play a role by disclosing the effects of the Cys allele on blood pressure, consequently uncovering the association between them.1A-AR, α1B-AR e α1C-AR) are G protein-coupled transmembrane receptors that mediate actions in the sympathetic nervous system through the binding of catecholamines[1-ARs, the α1A-AR is the predominant subtype in vascular smooth muscle. Genetically engineered knock-out mice for the α1A-AR have demonstrated that this subtype has a vasopressor role in resistance arteries and is required to maintain normal arterial blood pressure[1A-AR genetic variation to multiple pathophysiological conditions have been examined with negative results. However, most studies were carried in small sample sizes and underpowered to explore small effect-sizes and gene-environment interactions[Alpha1-adrenergic receptors  and other(s) SNP(s) may, in fact, be more relevant for the reported association[Our study has potential limitations: (1) perhaps a case-control study design may be more informative to evaluate the hypertension susceptibility than the present cross-sectional study; (2) blood pressure measurements were taken in only one visit instead of the more accepted procedure of three different medical visits; (3) our analysis has shown the existence of significant population structure and the statistical power associated to stratified ethnic subgroup analysis was significantly reduced in comparison with that associated to the whole population analysis; (4) we used the III Report of the National Cholesterol Education Program criteria to classify hypertension status. This procedure was applied in order to standardize the hypertension classification in both hypertensive individual and metabolic syndrome subjects. In this context, the present observations should be considered cautiously in relation to the pathology of hypertension and cardiovascular disease; (5) the functional role of Arg347Cys polymorphism is still unknown, but epidemiological studies have been suggesting that this molecular variant may be associated with blood pressure controlling mechanisms and hypertension status; (6) we have only genotyped the Arg347Cys SNP in the sociation. NeverthADRA1A Cys allele may have a discrete effect in individuals from the general population, it might become a relevant marker of the hypertension risk in individuals younger than 45-years. Moreover, these findings provide further insights for the understanding of the complex modulation of blood pressure by exercise activity. Future work should be carried-out in order to understand the context-dependent effect of the Arg347Cys variant regarding physical activity and to shed light on the potential role of ADRA1A genotype for predicting exercise-induced hypotension.Present data suggested that, although The authors declare that they have no competing interests.ACP conceived of the study, and participated in its design and coordination and in the statistical analysis and to draft the manuscript. SRF participated in the statistical analysis and helped to draft the manuscript. MSF carried out the molecular genetic analysis. JGM participated in the design of the study and performed the clinical analysis. JEK participated in the design of the study and coordination. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Previous studies have supported the association between hypertension and erectile dysfunction (ED). In addition, a significant correlation between hypertension in men and ED has been well established.The aim of this study was to investigate the prevalence of ED, its severity and other sexual function domains in hypertensive patients in Qatar.Cross-sectional study conducted between January and December 2006 at the Hamad General Hospital.Qatari and nonQatari nationals 25 to 75 years of age were approached to participate in this study, 642 (75.5%) gave their consent.Qatari and nonQatari men aged 25 to 75 years who gave consent were interviewed face-to-face. Sexual function was evaluated with the International index of erectile function.P=0.009), diabetes (P=0.022) for hypertriglyceridemia (P=0.033) and myocardial ischemia (P=0.042).A total of 642 (75.5%) men responded, mean age of subjects was 57.1 ± 11.9 years. The prevalence of ED in hypertensive patients was 58.3%. 21.2% of hypertensive men reported severe ED, 20.7% moderate ED and 16.4% mild ED. The comorbidities and risk factors were significantly more prominent in ED patients than in those with normal ED for hypercholesterolemia (Our results have shown a greater prevalence of ED in the hypertensive men in the population of Qatar. The presence of another risk factor in addition to elevated blood pressure can increase the likelihood of ED. The State of Qatar has witnessed a rapid change in many aspects of life during the last two decades. The discovery of oil in the mid-twentieth century has contributed to significant social change and Qatar, along with the other Gulf cooperation council (GCC) has experienced a rapid transition in its socioeconomic status. People in Qatar now enjoy a high standard of living; a substantial improvement over what had prevailed earlier. There has been a dramatic rise in the national economy expressed in terms of per capita income. In 2004, the gross domestic product of Qatar was higher than the rest of the GCC countries and estimated at US$ 28,270. The dramet al [et al[Erectile dysfunction (ED) is a very common condition among middle-aged men.–16 The M581013et al  reportedThe development of the International Index of Erectile Function (IIEF), a validated, self-administered, five-item questionnaire to evaluate male sexual function,–20 and a6This is a cross-sectional study aiming to investigate the prevalence of ED, its severity and other sexual function domains in hypertensive male patients attending internal medicine clinics at Hammed General Hospital, HMC in Qatar. The study was conducted between January and December 2006. Of the 850 hypertensive Qatari and nonQatari patients who were approached for the survey, 208 men were excluded from the study because either they declined to give their consent or they did not complete their questionnaires, resulting in 642 hypertensive patients (75.5%) being included in this study.Hypertension was diagnosed when the average of two or more diastolic blood pressure measurements on at least two subsequent visits (at least two weeks apart) was 90 mmHg or when the average of multiple systolic blood pressure readings on two or more subsequent visits was consistently equal or greater than 140 mmHg.4 All patSexual function was assessed with the Arabic-translated version of IIEF.–21 PriorApproval for the study was obtained from the medical ethics committee of the Hamad Medical Corporation. A consent form was obtained from the selected participants after the explanation of aims and the nature of the study. All interviews were conducted privately and confidentiality and anonymity of the participants was mainitained.t-test was used to ascertain the significance of differences between mean values of two continuous variables and Mann-Whitney was used as non-parametric test. Chi-square and Fisher exact test were performed to test for differences in proportions of categorical variables between two or more groups. Pearson's correlation coefficient was used to evaluate the strength of concordance between variables. The level P<0.05 was considered as the cutoff value for significance.Student The mean ± SD age of all patients was 57.1 ± 11.9 years (range 25 to 75). The mean patient age at the detection of hypertension was 48 ± 9.1 years. Patients received therapy a mean of 7.4 ± 2.6 years after the diagnosis of hypertension and were treated for a mean of 12 ± 7.9 years for the disease. Only 18% sought medical treatment for ED.2 = 7.10; P=0.009), similarly for diabetes , for hypertriglyceridemia  and myocardial ischemia  .P<0.01) was highly statistically significant.Furthermore, the Pearson's correlation between the duration of hypertension and the duration of weak erections (erectile function item of the IIEF) (r = 0.63, et al.[Although hypertension is considered a disease with few subjective symptoms, the rateet al. The diffet al. Our findet al. The Masset al. which iset al.–14 Theseet al.–21 Howevet al. Also, siet al.23In Greece ED was eA variety of physical and psychological factors are involved in erectile function and the alteration of one or more factors may lead to ED. Diabetes3610126101216Most of our patients were being treated for hypertension since a long duration with a mean and SD of 12 ± 7.9 years. Generally, up to 25% of ED cases were related to medication side-effects and antihypertensive drugs were the most implicated class. Many ant1014101314Even though most of our patients regularly visited their physicians, only 18% sought medical treatment for ED. We speculated that most patients with hypertension were more concerned about their high blood pressure level and its life-threatening conditions than about their erectile status. This suggests increased patient awareness about the medical treatment for ED.To the best of our knowledge, the current study is one of the few to investigate ED in patients with hypertension using a well-validated erectile function questionnaire all over the world–21 and tOur results have shown a greater prevalence of ED in the hypertensive men in the population of Qatar. The presence of another risk factor in addition to elevated blood pressure can increase the likelihood of ED.


To find out an easier way of reduction of intussusception during open surgery to avoid unnecessary bowel injury.Under general anesthesia, before laparotomy, warm normal saline was infused into the rectum with a Foley catheter and an intravenous drip set maintaining the level of the bottle at 80 cm above the operating table. After opening the abdomen, pressure was applied on the colon filled with normal saline distal to the intussusceptum. The pressure was transmitted to the intussusceptum and the walls of the intussuscipient and caused reduction of intussusception without any injury to the intussuscipient and intussusceptum. This procedure was performed on those patients on whom laparotomy was performed as a primary procedure due to nonavailability of fluoroscopy or ultrasonography.Between August 1998 and July 2005, we had six patients of mean (range) age 11 months (7–17 months). In two cases, at laparotomy, the intussusceptions were found to have already reduced.Gentle finger pressure is necessary for reduction of intussusception. This subjective “gentleness” is dependant on experience of the surgeon and varies from person to person. Focal pressure on the intussuscipient and apex of the intussusceptum by the finger during reduction may be more damaging than the diffusely transmitted hydrostatic pressure even by a less-experienced surgeon. This will avoid the needless resection and anastomosis of the intestine on many occasions. An intussusception is a surgical emergency, and delayed presentation is common in our country. Delay in treatment is a significant independent risk factor for increased morbidity and mortality. Some patFor logistic reasons, ultrasonographic and fluoroscopic cover were not available at certain times . In these situations, we had to perform primary laparotomy in five patients over a period of 7 years in a well-equipped institution and we tried hydrostatic reduction peroperatively.According to Daniel, “The intThe present study, with peroperative hydrostatic pressure, was performed to find out whether atraumatic reduction of gut in the intussusception is possible or not.We had the following inclusion criteria to perform this study: (1) patients with clinically confirmed intussusceptions, (2) delay in diagnosis of more than 48 h and (3) nonavailability of fluoroscopy and ultrasonography. From August 1998 to July 2005, we had six patients of mean (range) age of 11 months (7–17 months). One of the six patients was excluded from the study for a reason discussed below.Patients were resuscitated with intravenous (IV) fluids, nasogastric suction and antibiotics. All patients received two or three enemas before anesthesia. We consider this an important step. This cleans the distal bowel of fecal matter and prevents fecal soiling of the peritoneum in case of an accidental perforation. One patient had complete reduction of intussusception with this preoperative enema alone and was excluded from the report.The presence of a lump was reconfirmed by examination under anesthesia and a Foley catheter of the largest appropriate size (14–16F) for the patient was inserted into the rectum and the balloon was inflated. Normal saline warmed to body temperature was infused into the Foley catheter with an IV drip set, maintaining the saline bottle level at 80 cm above the operating table. Distenstion of the left flank and extension towards the right was visible.Laparotomies were performed through small right transverse incisions immediately above the umbilicus. On two occasions, at laparotomies, the intussusceptions were found reduced and only edematous and ecchymosed gut was seen. On three occasions, we applied pressure on the saline-filled intussuscipient, distal to the intussusceptum without exteriorizing the lump . This prIn no patient was resection of gut necessary. All patients had uneventful recovery. During the follow-up period [Mean (range) 46 (1–84) months], there was no recurrence.Initial diagnosis may be carried out by contrast enemas controlled by fluoroscopy or by ultrasonography.–6 ManageFrom our experience, focal pressure on the intussuscipient and the apex of the intussusceptum may be more damaging than a diffusely transmitted hydrostatic pressure by this procedure delivered by a less-experienced surgeon. This procedure seems to be helpful in reducing the rate of resection and anastomosis, the incidence of which at times maybe as high as 25%.This type of peroperative hydrostatic reduction may be helpful for the beginners and surgeons who do not come across the condition frequently and may also be suggested during laparoscopy.This study was performed on a small number of patients. Further studies are necessary to establish its superiority over standard reduction of intussusception by gentle finger pressure.


Gastroesophageal reflux and asthma, both of which are common conditions, often coexist in the same patient. Sir William Osler first observed the association between asthma and gastroesophageal reflux (GER). Since thThe reflux theory suggests that symptoms of asthma are due to reflux of acid into the oesophagus followed by aspiration into the proximal airway. On the oPrevious trials have had conflicting results regarding the beneficial effects of treatment with proton-pump inhibitors in patients with asthma who have frequent symptoms of GER disease. A systematic review of 12 small trials concluded that, although most of the studies showed that asthma-related outcomes were better when the patients were treated with proton-pump inhibitors. However,More recently, Littner and colleagues reported the results of a 6-month placebo-controlled trial involving 207 patients with moderate-to-severe asthma and definite symptoms of gastroesophageal reflux. Treatmen1, rescue-inhaler use, symptom scores, or nocturnal awakening. The esomeprazole-related improvement was most pronounced among patients who were taking long-acting beta-agonists.Kiljander and colleagues conducteIn light of above studies, current guidelines recommend that physicians consider evaluating patients who have poorly controlled asthma, especially those with night-time symptoms, for GER disease. If GER is present, treatment recommendations include the use of a proton-pump inhibitor. However, patients with asthma who are receiving treatment for GER incur substantially higher diagnostic and treatment costs than do patients with asthma of similar severity who are not receiving treatment for this diagnosis.Individuals with asthma are particularly prone to asymptomatic GER. As mentioned earlier, about half of patients with asthma who have GER have no symptoms. Whether Recently, in a parallel-group, double-blind trial, 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of GER were randomly assigned to receive either 40 mg of esomeprazole twice a day or matching placebo and followed up for 24 weeks.[This study differs from previous trials in that it excluded patients who had symptoms of GER twice or more times per week. The rationale was that these patients already have an indication for acid-suppression treatment, irrespective of their asthma. In the study population, authors found no benefit from proton-pump inhibitors with respect to any primary or secondary asthma-related outcome measure.Therefore, taken as a whole, the weight of evidence indicates that proton-pump inhibitors might improve the control of asthma in patients with moderate-to-severe persistent asthma having acid reflux symptoms. However, despite a high prevalence of asymptomatic GER among patients with poorly controlled asthma, treatment with proton-pump inhibitors does not improve asthma control. Asymptomatic GER is not a likely cause of poorly controlled asthma. Although widely practiced, proton-pump inhibitors should not be routinely prescribed for asthma symptoms if the patient does not have symptoms of GER.


Background Generally, scapula process fractures (coracoid and acromion) have been treated nonoperatively with favorable outcome, with the exception of widely displaced fractures. Very little has been published, however, regarding the operative management of such fractures and the literature that is available involves very few patients. Our hypothesis was that operative treatment of displaced acromion and coracoid fractures is a safe and effective treatment that yields favorable surgical results.Methods We reviewed 26 consecutive patients (27 fractures) treated between 1998 and 2007. Operative indications for these process fractures included either a painful nonunion, a concomitant ipsilateral operative scapula fracture, ≥ 1 cm of displacement on X-ray, or a multiple disruption of the superior shoulder suspensory complex. All patients were followed until they were asymptomatic, displayed radiographic fracture union, and had recovered full motion with no pain.Patients and results 21 males and 5 females, mean age 36 (18–67) years, were included in the study. 18 patients had more than one indication for surgery. Of the 27 fractures, there were 13 acromion fractures and 14 coracoid fractures. 1 patient was treated for both a coracoid and an acromion fracture. Fracture patterns for the acromion included 6 acromion base fractures and 7 fractures distal to the base. Coracoid fracture patterns included 11 coracoid base fractures and 3 fractures distal to the base. Mean follow-up was 11 (2–42) months. All fractures united and all patients had recovered full motion with no pain at the time of final follow-up. 3 patients underwent removal of hardware due to irritation from hardware components that were too prominent. There were no other complications.Interpretation While most acromion and coracoid fractures can be treated nonoperatively with satisfactory results, operative management may be indicated for displaced fractures and double lesions of the superior shoulder suspensory complex. Scapula process fractures of the coracoid and acromion have been given little consideration since they have traditionally been managed nonoperatively, often with favorable outcomes. The literature regarding the operative management of these process fractures is mostly comprised of case reports and small series, and is therefore scarce and anecdotal. As a result, neither operative indications nor operative results for these process fractures are well chronicled.Coracoid fractures most commonly occur through the base of the coracoid and are usually minimally displaced, unless there is an associated ipsilateral AC joint separation . NonoperWe hypothesized that operative treatment of displaced coracoid and acromion fractures is a safe and effective treatment. We assessed the surgical results of open reduction and internal fixation of these fractures.Between 1998 and 2007, all patients presenting with a highly displaced (≥ 1 cm) scapula fracture meeting criteria for operative management were enrolled in a prospective study monitoring the results of open reduction and internal fixation. All patients were managed by a single surgeon (PAC) at 1 of 2 level-1 trauma centers, which also served as a referral destination for management of scapula fractures.Operative indications for these process fractures included a painful nonunion, ≥ 1 cm of displacement upon radiographic evaluation, a multiple disruption of the superior shoulder suspensory complex , and a c26 patients met the inclusion criteria for this study. Patient demographics, associated ipsilateral upper extremity injuries, fracture classification/pattern, method of fixation, surgical results, and postoperative complications were recorded. Fractures were classified according to the AO/OTA classification . RadiogrViews that best visualized the fracture line in the plane represented by the standard scapula were collected for each patient and imported into Macromedia Fireworks MX software to overlap and orient fracture patterns onto a template scapula image. Images of each scapula were graphically superimposed to create a compilation of fracture lines on a standard scapula serving as the foundation for the bony anatomy of all patient fracture maps. The overlap of all major fracture lines resulted in a frequency diagram based on the density of fracture lines. Once proper anatomical alignment was obtained, fracture lines were identified and were traced on top of the combined 3D-CT and model scapula. Fracture patterns were then confirmed using the original 3D-CT rendering.Most coracoid fractures are fixed through a direct incision over the coracoid in Langer's lines. This may be a proximal extension of the deltopectoral approach, if a concomitant anterior or superior glenoid fracture is being addressed. The surgeon must dissect down the cephalad slope of the coracoid to its base until the fracture is appreciated and can be reduced anatomically, mobilizing the coracoclavicular ligaments for proper visualization. A simple 3.5-mm lag screw is often all that is needed for adequate stability. A one-quarter tubular plate along the cephalad slope spanning the fracture may also be warranted. In cases where a coracoid base fracture involves a portion of the superior glenoid fossa . Shoulder motion was measured in degrees using a goniometer and shoulder strength was measured in pounds of force using a hand-held dynamometer. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire  and ShorThe procedures followed in this study were in accordance with the ethical standards of the responsible committee on human experimentation, and with the Helsinki Declaration of 1975, as revised in 2000. The study design and enrollment process complied with all guidelines of the respective Institutional Review Boards .Of 156 patients with scapula fractures, 26 patients  years) underwent operative management for a coracoid and/or acromion fracture (Table 1 of Supplementary data). Of the 27 fractures, there were 13 acromion fractures (OTA type A1.1) and 14 coracoid fractures (OTA type A2.1). 1 patient (no. 5) was treated for both a coracoid fracture and an acromion fracture. Fracture patterns for the acromion included 6 acromial base fractures, 4 proximal acromion fractures, and 3 fractures midway along the acromion. Coracoid fracture patterns included 11 coracoid base fractures and 3 fractures midway along the coracoid. .Overlay of the fractures yielded illustrations of the coracoid and acromion fracture patterns and demonstrated the morphological variation with which these fracture patterns occurred  and 2. TOperative indications included a painful acromion base nonunion in 2 patients , a concoThe method of fixation for coracoid fractures included cortical lag screw placement in all 14 cases  with sup8 of the 26 patients were treated at the previous institution of the senior author (PAC), at which time quantitative functional outcomes were not formally obtained as part of follow-up visits. Of the remaining 18 patients that were treated at the senior author's current institution, functional outcomes were obtained for 13 patients at a mean follow-up of 22 (12–42) months .All 13 patients were pain-free at rest and when using the affected upper extremity. The mean DASH score was 7 (0–26) for this subset of patients, compared to the mean normative DASH score for the uninjured population of 10. The mean SF-36 scores in all 8 parameters for the study patients were similar to the mean scores of the normal population. . A lower DASH score on a 100-point scale translates into a better outcome, and a higher SF-36 score on a 100-point scale also reflects a better outcome. Patient 14 sustained a T12 spinal cord paralysis as a result of his injury; therefore, DASH and SF-36 scores could not be obtained for this patient. Patient 17 sustained a severe brachial plexus injury such that he had no use of the injured upper extremity. Even so, because he had complete use of his contralateral, uninjured extremity, a DASH score and SF-36 scores were obtainable although range-of-motion and strength measurements could not be obtained. All of these patients, with the exception of patients 14 and 17, returned to their previous occupations and activities.Patient 8 underwent complete removal of hardware due to prominence and irritation over the acromion. Another patient (no. 19) experienced hardware loosening, whereby a screw had backed out from a reconstruction plate applied to the acromion, causing irritation to the surrounding tissue. This screw was removed operatively. Patient 20, treated for a coracoid fracture, required excision of ectopic bone impinging on the conjoint tendon. There were no wound complications, infections, or malunions in this series.Scapula fractures are uncommon; they account for 1% of all fractures . Of thesUnder most circumstances, undisplaced or minimally displaced coracoid or acromion fractures can be managed nonoperatively with satisfactory results . Even soThe indications for operative management and its safety and efficacy in the treatment of these fractures are yet to be established. To date, the largest operative series for coracoid and acromion fractures include 35 patients (of 67 with fracture) and 8 patients (of 37 with fracture), respectively, both described by Operative techniques described for open reduction and internal fixation of coracoid fractures include interfragment screw fixation with cortical lag screws for larger fragments  and nonaA variety of fixation techniques have been described for the open reduction and internal fixation of acromion fractures, including tension band wiring for more distal fractures , plate fIn this article we have reported the clinical and surgical results of 26 operatively managed acromion or coracoid fractures. All of the patients in this series were followed until they had pain-free range of motion, had no tenderness at the fracture site, and displayed fracture union upon radiographic evaluation. Quantitative functional outcomes were obtained for 13 of these patients, which showed a good to excellent overall outcome. The mean DASH score was 7, which is lower than the normative mean score for an uninjured population (10). The mean SF-36 scores in all 8 parameters were comparable to the normative mean scores, and in some parameters these patients scored higher than the normative mean. Soft tissue irritation due to prominent hardware is a minor reported complication  that occA limitation of our study is that our cohort was limited to operatively managed process fractures; thus, we are unable to compare treatment results in nonoperative patients. Our study was not designed to be able to answer the question of whether patients will do better with nonoperative or operative management. We cannot therefore state definitively when to or when not to manage a coracoid or acromion fracture operatively. Our intention with this study was to elucidate operative complications and rate of healing of the fracture, and also to describe fracture patterns and the fixation strategy employed. Our study only demonstrates that in experienced hands operating on a coracoid or acromion fracture with a certain indication, displacement of > 1 cm, is safe and can result in successful fracture union and pain-free motion.


Identifying the determinants of health-related quality of life (HRQOL) in patients with systolic heart failure (CHF) is rare in primary care; studies often lack a defined sample, a comprehensive set of variables and clear HRQOL outcomes. Our aim was to explore the impact of such a set of variables on generic and disease-specific HRQOL.In a cross-sectional study, we evaluated data from 318 eligible patients. HRQOL measures used were the SF-36  and four domains of the KCCQ . Potential determinants (instruments) included socio-demographical variables , clinical ), depression (PHQ-9), behavioural (EHFScBs and prescribing) and provider (e.g. list size of and number. of GPs in practice) variables. We performed linear (mixed) regression modelling accounting for clustering.Patients were predominantly male (71.4%), had a mean age of 69.0 (SD: 10.4) years, 12.9% had major depression, according to PHQ-9. Across the final regression models, eleven determinants explained 27% to 55% of variance : Depression ; age ; multimorbidity ; list size ; SES ; and each of the following once: no. of GPs per practice, NYHA class, COPD, history of CABG surgery, aldosterone antagonist medication and Self-care (0.1/-0.2/-0.2/0.1/-0.1/-0.2).HRQOL was determined by a variety of established individual variables. Additionally the presence of multimorbidity burden, behavioural (self-care) and provider determinants may influence clinicians in tailoring care to individual patients and highlight future research priorities. Chronic systolic heart failure (CHF) is a common clinical syndrome, with increasing incidence at older age, and is associated with high mortality rates, and compromised health-related quality of life (HRQOL) . MoreoveThe objectives of CHF treatment are to maximise life expectancy, improve HRQOL and prevent disease progression and admissions . OptimalHRQOL is a multidimensional concept comprised of several domains, including physical/biological factors, symptom status, functional status, health perceptions, and overall well-being . In rese2, multimorbidity, BNP [Many previous studies have deepened the understanding about what factors can determine HRQOL in CHF, not least to identify intervention targets for improved outcome. They have been performed in various sectors and settings, mostly in secondary care or post-discharge setting -22, someity, BNP -17,20-25ity, BNP ) determiity, BNP ,25 vs. sity, BNP ,23,24) lGiven there is little evidence for patients with CHF recruited in primary care, our aim was to identify and explore the impact of determinants of generic and disease-specific HRQOL with respect to a wide set of individual and provider variables. We focused on an exploratory comparison between generic and disease-specific HRQOL.subproject 10 "quality of life" within the German "Competence Network Heart Failure", sponsored by the Federal Ministry of Education and Research [This study was conducted as a cross-sectional study of pooled baseline data of Research . Within Research -30. BothResearch  and wereInterested GPs were eligible for participation if they were certified as a primary care physician or equivalent and practiced as a statutory health insurance affiliated physician. Fifty general practitioners (GPs) from 48 practices participated in the two studies in one region of Northern Baden, Germany.Eligible patients were adults ≥ 40 years with confirmed systolic heart failure (CHF) with stable symptoms at the time of inclusion, and diagnosis of a chronic, irreversible CHF at least 2 weeks prior to inclusion. CHF diagnosis was based on dyspnea (NYHA) and objective measurement (e.g. by echocardiography) of impaired left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%). Criteria slightly differed between the TTT-trial and HICMan-trial regarding the cut-off and actuality of the determination of left ventricular ejection fraction  and dyspnea . Exclusion criteria were: Primary valvular heart diseases and relevant hemodynamic effects, hypertrophic obstructive/restrictive cardiomyopathy (HOCM/RCM), and people with a concomitant terminal illness, addictive disorders , dementia or severe psychological illness ,30.All GPs and patients gave written informed consent. 367 eligible patients were recruited, 168 within TTT (enrolment of patients and data collection: March to September 2005) and 199 within HICMan (enrolment of patients and data collection: June 2006 to January 2007), details have been described elsewhere ,30. WithGPs received an initiation visit by a study nurse including an introduction to the trial's investigator file. GPs collected and documented organisational , physicians' individual (e.g. years in practice) and patients' individual clinical data  on pre-specified case report forms (CRFs) according to the Basic Clinical Dataset (BCD) of the Competence Network Heart Failure . The docParallel to the clinical baseline assessment, patient-reported questionnaires were handed out by practice personnel.A sociodemographic dataset was obtained from all patients . For genDepression was assessed using the German version of the Patient Health Questionnaire depression module (PHQ-9) . It consThe European Heart Failure Self-Care Behaviour Scale  is a 12-item, self-administered questionnaire regarded as a valid, reliable and practical scale to measure the self-reported self-care behaviour of heart failure patients, for example, daily weighing, fluid restriction, exercise or contacting a health care provider . Scores To allow comparisons across the two HRQOL measures we decided a priori to focus on summary measures, i.e. the PCS and MCS (SF-36), and Functional status,  Quality of life, Self efficacy and Social function (KCCQ), all distinct domains that differentiate most adequately between 'physical' and 'psychosocial' aspects of HRQOL. Therefore, we omitted KCCQ-os as it represents aggregated scales of both aspects, rendering a comparison with generic HRQOL (PCS and MCS) difficult.Our choice of variables to be analysed with respect to their predictive value was based on the literature and clinical reasoning. We selected variables of the provider and individuals respectively as shown in tables Dummy variables were built for all ordinal variables . We aggregated NYHA functional class I with II and II with IV accounting for the low number of observations in the classes I and IV. As NT-proBNP had a skewed distribution, logarithmic transformation was performed as described and performed previously ,56. AlcoPearson correlation coefficients were calculated for analyses of relationships between numerical explanatory variables and the dependent variable. In the following, Creatinin-clearance was omitted due to collinearity with age, which correlated consistently higher with dependent variables.2) we present the results of the unified regression models. For analyses we used Stata/MP version 10.1, SPSS version 16.0.2 (SPSS Inc.) and SAS 9.2 (PROC MIXED).Variables with a p-value less than 0.05 were entered into multiple regression analyses using the forward selection algorithm. As this procedure uses only those individuals who have complete information on all explanatory variables results were validated in unified regression models. All explanatory variables remained within the models, except for NYHA functional class for PCS and Hypertension for  Quality of life (KCCQ). To account for the clustering of data (intraclass correlation within each practice attributable to clustering) we performed linear mixed effects regression models with the physician as a random effects model nested within groups. Regression coefficients were the same; the few exceptions regarding explanatory variables are reported. Given the possibility to inform about the amount of explained variance , KCCQ domains and summary scores are shown in Table Table S1  variables, i.e. a greater (patient) list size impacted negatively on the MCS and Self efficacy, whereas a higher number of physicians per practice determined MCS positively.Among sociodemographic factors, age remained in four of the overall six models , and a higher socio-economic status in PCS and Self efficacy (β: 0.14 to 0.23).NYHA functional class contributed only to the explained variance of the disease-specific summary scale Functional Status (β: -0.16), whereas COPD for the generic summary PCS (β: -0.15).A history of CABG surgery determined the generic HRQOL summary MCS positively (β: 0.09) and the prescription of an aldosterone antagonist the KCCQ domain Social limitation negatively (β: -0.13). Aggregated physician-rated multimorbidity (CIRS-G) contributed to the explained variance in generic and specific scales  Quality of life and Social limitation; β: -0.09 to -0.14).Better self-care behaviour  contributed significantly to the KCCQ domain Self efficacy (β: -0.21).Depression severity (PHQ-9 summary score) was a significant determinant of generic and disease-specific HRQOL in all models, and had the strongest impact (β: -0.3 to -0.72) on each summary scale of HRQOL in comparison to other determinants.In a clearly defined convenience sample of outpatients with stable systolic chronic heart failure (CHF), we could explore determinants of generic and disease-specific health-related quality of life (HRQOL) using a wide set of explanatory variables. Generic and disease-specific HRQOL varies but is considerably impaired in these patients. They demonstrated good Heart failure self-care behaviour but a considerable burden of (multi-)morbidity. We explored the impact of sociodemographic variables, objective measures of heart failure severity, somatic and depressive comorbidity, behavioural and provider variables on the variance of generic and disease-specific HRQOL in patients with CHF using multiple linear regression analyses. Eleven determinants were independently associated with generic and/or disease-specific HRQOL: These were depression severity, physician-rated morbidity burden, increasing age, bigger list size, higher NYHA functional class, COPD, prescription of aldosterone antagonist determined worse, whereas more GPs (per practice), a higher socio-economic status, better Self-care and history of CABG surgery determined better HRQOL.A considerable number of studies have led to conceptual models of HRQOL in relation to CHF that describe the interactive relationships between pathophysiology, symptoms , functional and psychological aspects . AccordiOur results regarding the impact of objective measures such as EF and BNP on HRQOL are similar to previous literature: For example, while BNP correlated bivariately with HRQOL scales, it did not remain in the multivariate regression analyses with included (known) correlates such as NYHA functional class. Therefore, decreased EF or elevated BNP seems not to be sensed by the individual, but the associated symptoms or functional status ,17.Depression severity as assessed by the summary score of the PHQ-9 had by far the greatest impact on HRQOL variance in all six investigated summary scores or domains, a finding that is in line with previous findings: Gott et al. found depression, measured by a geriatric depression scale, determining generic and specific HRQOL (summary scores of SF-36 and KCCQ) in a cross-sectional study with 542 elderly (mean age 77 years) patients in primary care, a sample where the diagnosis of CHF was validated by the GP . In our In this study, NYHA functional class determined KCCQ Functional Status, but not the Physical Component summary of the SF-36. There, COPD, a disease characterised also by 'dyspnea' was independently associated. These findings are supportive for the higher specificity of the KCCQ than the SF-36 with regard to the cardinal symptoms of CHF.Moreover, our results regarding the role of disease severity (NYHA class) and Depression (PHQ-9 summary score) in disease-specific HRQOL (KCCQ) are in line with Faller et al. . They in2 0.18), but not within the MCS [Notably, physician-rated overall morbidity burden (multimorbidity) was considerable (CIRS summary score) and determined HRQOL in 4 of 6 investigated models, i.e. in the PCS of the SF-36, but not MCS, and in all KCCQ models, except for Self efficacy. Studies that investigate co-/multi-morbidity in relation to HRQOL of patients with CHF usually account for single diseases and/or count the no. of conditions and rarely used the CIRS instrument: We included the CIRS additionally to certain single conditions as a physician-rated disease severity aggregate accounting for all body systems would better reflect the patients' disease burden. Regarding generic HRQOL, our results are consistent to a study in primary care with a sample of 238 patients with chronic diseases: The CIRS played a role within the PCS  impacted on KCCQ Self efficacy and SF-36 PCS. Little is known regarding this aspect in relation to CHF. In the study of Gott et al. lower SES impacted negatively on MCS and KCCQ overall scores , and eduA larger practice list size was associated with worse HRQOL (MCS and Self efficacy), whereas a higher number of GPs per practice counterbalanced this observed association (in MCS), which is a new finding, as there is little evidence for the impact of organizational aspects, i.e. practice factors, on HRQOL in CHF in routine care. Moreover, our variables on organization  were not comprehensive.However, some literature on practice performance and patient satisfaction shows associations within the organization of primary care that cannot be fully explained -70: In asureness on what to do if heart failure worsens and about the patient's understanding of the ability to prevent worsening of CHF . According to the European Clinical Practice Guideline for CHF, HF self care can be defined as action aimed at clinical stability, avoidance of behaviour that can worsen the condition, and early detection of symptoms of deterioration. Self care management is regarded as a key issue of successful treatment and can significantly impact on health outcomes [The EHFScBS scores that aggregate the actual patient-reported self-care behaviour 12 items) were associated with KCCQ Self efficacy (2 items), as expected, although the two instruments ask not completely the same concepts: The instruments differ in that the EHFScBS asks for patient's agreement on defined 12 behaviours, and the KCCQ Self efficacy asks about patient's  items weoutcomes . The autA number of limitations should be stated: The cross-sectional design of our study implies that no cause-effect relationship between variables can be established. The explorative approach rather implies the identification of independent associations, whereas predictive value needs to be validated in consecutive studies. A known dilemma exists between internal validity and generalisability: Participants of the parental trials might not be representative for the population, e.g. because elderly patients may decline to participate because of effort. On the other hand, it can be regarded as strength - contrary to most other studies in primary care - the sample consisted of patients with defined CHF, so more valid statements can be made regarding this patient group.Most complete models were obtained for KCCQ Functional Status and  Quality of life, whereas most missings pertained to SF-36 summary scores, socio-economic status and self-care. We abstained from imputation methods as they have their own limitations. We did not perform a non-responder analysis, but regard our approach in the context of exploration as appropriate.Considerably impaired and varying health-related Quality of life (HRQOL) of patients with systolic heart failure in primary care could be explained by known determinants in different patterns and to various extents across generic and disease-specific concepts of HRQOL, such as age, social status, depression symptoms and disease severity. Patients' perceptions of disease severity  were the strongest determinants, whereas, physician-rated multimorbidity (morbidity burden) also impacts independently on HRQOL - more than findings in previous studies suggest. New potentially relevant variables, i.e. organisational aspects of primary care, need to be confirmed in future studies. Our results also corroborate the ongoing challenge of holistic care for elderly (multimorbid) patients (with CHF) in primary care. Information about patient and provider-related determinants of HRQOL in patients with CHF may help in providing individually tailored care.A2RA: Angiotensin-2 receptor antagonist; ACE: Angiotensin converting enzyme; CCCT: Coordination Centre Clinical Trials; CABG: Coronary artery bypass graft surgery; CHD: Coronary heart disease; CHF: Chronic (systolic) heart failure; CI: Confidence interval; CIRS-G: Cumulative illness rating scale, geriatric; COPD: Chronic obstructive pulmonary disease; EHFScBS: European Heart Failure Self-care Behaviour Scale; GFR: Glomerular filtration rate; GP: General practitioner; HICMan: Heidelberg Integrated Case management; HRQOL: Health-related quality of life; ICD: Implantable cardioverter defibrillator; KCCQ: Kansas City Cardiomyopathy Questionnaire; LVEF: Left ventricular ejection fraction; LVSD: Left ventricular systolic dysfunction; NT-proBNP: N-terminal Brain Natriuretic Peptide; NYHA: New York Heart Association; MCS: Mental Component Summary (of SF-36); PAD: Peripheral arterial disease; PCS: Physical Component Summary (of SF-36); PHQ-9: Depression module of the Patient Health Questionnaire; PTCA: Percutaneous Transluminal Coronary Angioplasty; RCT: Randomised controlled trial; SF-36: MOS 36-item short-form health survey; TTT: Train the trainer The authors declare that they have no competing interests.FPK, CUK and TMT designed the study. CUK, GL and FPK analysed the results. All authors interpreted the results. FPK wrote the manuscript, and all authors contributed to writing revisions and approved the final manuscript. FPK is the guarantor.Table S1: Determinants of generic (SF-36) and disease-specific (KCCQ) health-related quality of life (HRQOL)Click here for file