***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Cluster r and omized trials are frequently used in health service evaluation . It is common practice to use an analysis model with a r and om effect to allow for clustering at the analysis stage . In design s where clusters are exposed to both control and treatment conditions , it may be of interest to examine treatment effect heterogeneity across clusters . In design s where clusters are not exposed to both control and treatment conditions , it can also be of interest to allow heterogeneity in the degree of clustering between arms . These two types of heterogeneity are related . It has been proposed in both parallel cluster trials , stepped‐wedge , and other cross‐over design s that this heterogeneity can be allowed for by incorporating additional r and om effect(s ) into the model . Here , we show that the choice of model parameterization needs careful consideration as some parameterizations for additional heterogeneity induce unnecessary or implausible assumptions . We suggest more appropriate parameterizations , discuss their relative advantages , and demonstrate the implication s of these model choices using a real example of a parallel cluster trial and a simulated stepped‐wedge trial BACKGROUND During cardiopulmonary resuscitation ( CPR ) in patients with out-of-hospital cardiac arrest , the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival . We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations . METHODS This cluster-r and omized trial with crossover included 114 emergency medical service ( EMS ) agencies . Adults with non-trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions ( intervention group ) or interrupted chest compressions ( control group ) . The primary outcome was the rate of survival to hospital discharge . Secondary outcomes included the modified Rankin scale score ( on a scale from 0 to 6 , with a score of ≤3 indicating favorable neurologic function ) . CPR process was measured to assess compliance . RESULTS Of 23,711 patients included in the primary analysis , 12,653 were assigned to the intervention group and 11,058 to the control group . A total of 1129 of 12,613 patients with available data ( 9.0 % ) in the intervention group and 1072 of 11,035 with available data ( 9.7 % ) in the control group survived until discharge ( difference , -0.7 percentage points ; 95 % confidence interval [ CI ] , -1.5 to 0.1 ; P=0.07 ) ; 7.0 % of the patients in the intervention group and 7.7 % of those in the control group survived with favorable neurologic function at discharge ( difference , -0.6 percentage points ; 95 % CI , -1.4 to 0.1 , P=0.09 ) . Hospital-free survival was significantly shorter in the intervention group than in the control group ( mean difference , -0.2 days ; 95 % CI , -0.3 to -0.1 ; P=0.004 ) . CONCLUSIONS In patients with out-of-hospital cardiac arrest , continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC CCC Clinical Trials.gov number , NCT01372748 . ) Objective To investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation outside hospital increases the proportion of subjects who achieved prehospital return of spontaneous circulation .  Design A cluster-r and omised trial . Subjects 1586 people having cardiac arrest outside hospital in whom resuscitation was attempted by emergency medical services ( 771 procedures without feedback , 815 with feedback ) . Setting Emergency medical services from three sites within the Resuscitation Outcomes Consortium in the United States and Canada . Intervention Real-time audio and visual feedback on cardiopulmonary resuscitation ( CPR ) provided by the monitor-defibrillator . Main outcome measure Prehospital return of spontaneous circulation after CPR . Results Baseline patient and emergency medical service characteristics did not differ between groups . Emergency medical services muted the audible feedback in 14 % of cases during the period with feedback . Compared with CPR clusters lacking feedback , clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided ( 64 % v 66 % , cluster-adjusted difference 1.9 ( 95 % CI 0.4 to 3.4 ) ) , increased compression depth ( 38 v 40 mm , adjusted difference 1.6 ( 0.5 to 2.7 ) ) , and decreased proportion of compressions with incomplete release ( 15 % v 10 % , adjusted difference −3.4 ( −5.2 to −1.5 ) ) . However , frequency of prehospital return of spontaneous circulation did not differ according to feedback status ( 45 % v 44 % , adjusted difference 0.1 % ( −4.4 % to 4.6 % ) ) , nor did the presence of a pulse at hospital arrival ( 32 % v 32 % , adjusted difference −0.8 ( −4.9 to 3.4 ) ) , survival to discharge ( 12 % v 11 % , adjusted difference −1.5 ( −3.9 to 0.9 ) ) , or awake at hospital discharge ( 10 % v 10 % , adjusted difference −0.2 ( −2.5 to 2.1 ) ) . Conclusions Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines . However , these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes . Trial Registration Clinical Trials Background Computer-based decision support has been effective in providing alerts for preventive care . Our objective was to determine whether a personalized asthma management computer-based decision support increases the quality of asthma management and reduces the rate of out-of-control episodes . Methods A cluster-r and omized trial was conducted in Quebec , Canada among 81 primary care physicians and 4447 of their asthmatic patients . Patients were followed from the first visit for 3–33 months . The physician control group used the Medical Office of the 21st century ( MOXXI ) system , an integrated electronic health record . A custom-developed asthma decision support system was integrated within MOXXI and was activated for physicians in the intervention group . Results At the first visit , 9.8 % ( intervention ) to 12.9 % ( control ) of patients had out-of-control asthma , which was defined as a patient having had an emergency room visit or hospitalization for respiratory-related problems and /or more than 250 doses of fast-acting β-agonist ( FABA ) dispensed in the past 3 months . By the end of the trial , there was a significant increase in the ratio of doses of inhaled corticosteroid use to fast-acting β-agonist ( 0.93 vs. 0.69 : difference : 0.27 ; 95 % CI : 0.02–0.51 ; P = 0.03 ) in the intervention group . The overall out-of-control asthma rate was 54.7 ( control ) and 46.2 ( intervention ) per 100 patients per year ( 100 PY ) , a non-significant rate difference of −8.7 ( 95 % CI : −24.7 , 7.3 ; P = 0.29 ) . The intervention ’s effect was greater for patients with out-of-control asthma at the beginning of the study , a group who accounted for 44.7 % of the 5597 out-of-control asthma events during follow-up , as there was a reduction in the event rate of −28.4 per 100 PY ( 95 % CI : −55.6 , −1.2 ; P = 0.04 ) compared to patients with in-control asthma at the beginning of the study ( −0.08 [ 95 % CI : −10.3 , 8.6 ; P = 0.86 ] ) . Discussion This study evaluated the effectiveness of a novel computer-assisted ADS system that facilitates systematic monitoring of asthma control status , follow-up of patients with out of control asthma , and evidence -based , patient-specific treatment recommendations . We found that physicians were more likely to use ADS for out-of-control patients , that in the majority of these patients , they were advised to add an inhaled corticosteroid or a leukotriene inhibitor to the patient s treatment regimen , and the intervention significantly increased the mean ratio of inhaled corticosteroids to FABA during follow-up . It also reduced the rate of out-of-control episodes during follow up among patients whose asthma was out-of-control at the time of study entry . Future research should assess whether coupling patient-specific treatment recommendations , automated follow-up , and home care with comparative feedback on quality and outcomes of care can improve guideline adoption and care outcomes . Conclusions A primary care-personalized asthma management system reduced the rate of out-of-control asthma episodes among patients whose asthma was poorly controlled at the study ’s onset . Trial Registration Clinical trials.gov Identifier : NCT00170248 http:// clinical Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Patients at risk of severe exacerbations contribute disproportionally to  asthma mortality , morbidity and costs . We evaluated the effectiveness and costs of using ‘ asthma risk registers ’ for these patients in primary care . Methods In a cluster-r and omised trial , 29 primary care practice s identified 911 at-risk asthma patients using British asthma guideline criteria ( severe asthma plus adverse psychosocial characteristics ) . Intervention practice s added electronic alerts to identified patients ' records to flag their at-risk status and received practice -based training about using the alerts to improve patient access and opportunistic management . Control practice s continued routine care . Numbers of patients experiencing the primary outcome of a moderate-severe exacerbation ( result ing in death , hospitalisation , accident and emergency attendance , out-of-hours contact , or a course/boost in oral prednisolone for asthma ) , other healthcare and medication usage , and costs over 1 year were derived from practice -based records . Results There was no significant effect on exacerbations ( control : 46.5 % ; intervention : 53.6 % , OR , 95 % CI 1.30 , 0.93 to 1.80 ) . However , this composite outcome masked relative reductions in intervention patients experiencing hospitalisations ( OR 0.50 , 95 % CI 0.26 to 0.94 ) , accident and emergency ( OR 0.74 , 95 % CI 0.42 to 1.31 ) and out-of-hours contacts ( OR 0.79 , 95 % CI 0.45 to 1.37 ) ; and a relative increase in prednisolone prescription for exacerbations ( OR 1.31 , 95 % CI 0.92 to 1.85 ) . Furthermore , prescription of nebulised short-acting β-agonists reduced and long-acting β-agonists increased for intervention relative to control patients . The adjusted mean per patient healthcare cost was £ 138.21 lower ( p=0.837 ) among intervention practice s. Conclusion Using asthma risk registers in primary care did not reduce treated exacerbations , but reduced hospitalisations and increased prescriptions of recommended preventative therapies without increasing costs Objective To evaluate the effectiveness of a structured education pulmonary rehabilitation programme on the health status of people with chronic obstructive pulmonary disease ( COPD ) . Design Two-arm , cluster r and omised controlled trial . Setting 32 general practice s in the Republic of Irel and . Participants 350 participants with a diagnosis of moderate or severe COPD . Intervention Experimental group received a structured education pulmonary rehabilitation programme , delivered by the practice nurse and physiotherapist . Control group received usual care . Main outcome measure Health status as measured by the Chronic Respiratory Question naire ( CRQ ) at baseline and at 12–14 weeks postcompletion of the programme . Results Participants allocated to the intervention group had statistically significant higher mean change total CRQ scores ( adjusted mean difference ( MD ) 1.11 , 95 % CI 0.35 to 1.87 ) . However , the CI does not exclude a smaller difference than the one that was prespecified as clinical ly important . Participants allocated to the intervention group also had statistically significant higher mean CRQ Dyspnoea scores after intervention ( adjusted MD 0.49 , 95 % CI 0.20 to 0.78 ) and CRQ Physical scores ( adjusted MD 0.37 , 95 % CI 0.14 to 0.60 ) . However , CIs for both the CRQ Dyspnoea and CRQ Physical subscales do not exclude smaller differences as prespecified as clinical ly important . No other statistically significant differences between groups were seen . Conclusions A primary care based structured education pulmonary rehabilitation programme is feasible and may increase local accessibility to people with moderate and severe COPD . Trial registration IS RCT N52403063 The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 200 
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Baseline demographic reporting was high for age and sex in CRTs , but was uncommon for race and ethnicity .
HTE analyses were uncommon and was rare for demographic subgroups , which limits the ability to examine the extent of benefits or risks for treatments tested with CRT design