Admission avoidance hospital at home.

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that would otherwise require acute hospital inpatient care, and always for a limited time period. This is the fourth update of this review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL on 24 February 2022, and checked the reference lists of eligible articles. We sought ongoing and unpublished studies by searching ClinicalTrials.gov and WHO ICTRP, and by contacting providers and researchers involved in the field. SELECTION CRITERIA: Randomised controlled trials recruiting participants aged 18 years and over. Studies comparing admission avoidance hospital at home with acute hospital inpatient care. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. We performed meta-analysis for trials that compared similar interventions, reported comparable outcomes with sufficient data, and used individual patient data when available. We used the GRADE approach to assess the certainty of the body of evidence for the most important outcomes. MAIN RESULTS: We included 20 randomised controlled trials with a total of 3100 participants; four trials recruited participants with chronic obstructive pulmonary disease; two trials recruited participants recovering from a stroke; seven trials recruited participants with an acute medical condition who were mainly older; and the remaining trials recruited participants with a mix of conditions. We assessed the majority of the included studies as at low risk of selection, detection, and attrition bias, and unclear for selective reporting and performance bias. For an older population, admission avoidance hospital at home probably makes little or no difference on mortality at six months' follow-up (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.68 to 1.13; P = 0.30; I2 = 0%; 5 trials, 1502 participants; moderate-certainty evidence); little or no difference on the likelihood of being readmitted to hospital after discharge from hospital at home or inpatient care within 3 to 12 months' follow-up (RR 1.14, 95% CI 0.97 to 1.34; P = 0.11; I2 = 41%; 8 trials, 1757 participants; moderate-certainty evidence); and probably reduces the likelihood of living in residential care at six months' follow-up (RR 0.53, 95% CI 0.41 to 0.69; P < 0.001; I2 = 67%; 4 trials, 1271 participants; moderate-certainty evidence). Hospital at home probably results in little to no difference in patient's self-reported health status (2006 patients; moderate-certainty evidence). Satisfaction with health care received may be improved with admission avoidance hospital at home (1812 participants; low-certainty evidence); few studies reported the effect on caregivers. Hospital at home reduced the initial average hospital length of stay (2036 participants; low-certainty evidence), which ranged from 4.1 to 18.5 days in the hospital group and 1.2 to 5.1 days in the hospital at home group. Hospital at home length of stay ranged from an average of 3 to 20.7 days (hospital at home group only). Admission avoidance hospital at home probably reduces costs to the health service compared with hospital admission (2148 participants; moderate-certainty evidence), though by a range of different amounts and using different methods to cost resource use, and there is some evidence that it decreases overall societal costs to six months' follow-up. AUTHORS' CONCLUSIONS: Admission avoidance hospital at home, with the option of transfer to hospital, may provide an effective alternative to inpatient care for a select group of older people who have been referred for hospital admission. The intervention probably makes little or no difference to patient health outcomes; may improve satisfaction; probably reduces the likelihood of relocating to residential care; and probably decreases costs.

Methods to increase response to postal and electronic questionnaires.

BACKGROUND: Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH METHODS: We searched 14 electronic databases up to December 2021 and manually searched the reference lists of relevant trials and reviews. We contacted the authors of all trials or reviews to ask about unpublished trials; where necessary, we also contacted authors to confirm the methods of allocation used and to clarify results presented. SELECTION CRITERIA: Randomised trials of methods to increase response to postal or electronic questionnaires. We assessed the eligibility of each trial using pre-defined criteria. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity amongst trial odds ratios using a Chi2 test and quantified the degree of inconsistency between trial results using the I2 statistic. MAIN RESULTS: Postal We found 670 eligible trials that evaluated over 100 different strategies of increasing response to postal questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response almost doubled when: using monetary incentives (odds ratio (OR) 1.86; 95% confidence interval (CI) 1.73 to 1.99; heterogeneity I2 = 85%); using a telephone reminder (OR 1.96; 95% CI 1.03 to 3.74); and when clinical outcome questions were placed last (OR 2.05; 95% CI 1.00 to 4.24). The odds of response increased by about half when: using a shorter questionnaire (OR 1.58; 95% CI 1.40 to 1.78); contacting participants before sending questionnaires (OR 1.36; 95% CI 1.23 to 1.51; I2 = 87%); incentives were given with questionnaires (i.e. unconditional) rather than when given only after participants had returned their questionnaire (i.e. conditional on response) (OR 1.53; 95% CI 1.35 to 1.74); using personalised SMS reminders (OR 1.53; 95% CI 0.97 to 2.42); using a special (recorded) delivery service (OR 1.68; 95% CI 1.36 to 2.08; I2 = 87%); using electronic reminders (OR 1.60; 95% CI 1.10 to 2.33); using intensive follow-up (OR 1.69; 95% CI 0.93 to 3.06); using a more interesting/salient questionnaire (OR 1.73; 95% CI 1.12 to 2.66); and when mentioning an obligation to respond (OR 1.61; 95% CI 1.16 to 2.22). The odds of response also increased with: non-monetary incentives (OR 1.16; 95% CI 1.11 to 1.21; I2 = 80%); a larger monetary incentive (OR 1.24; 95% CI 1.15 to 1.33); a larger non-monetary incentive (OR 1.15; 95% CI 1.00 to 1.33); when a pen was included (OR 1.44; 95% CI 1.38 to 1.50); using personalised materials (OR 1.15; 95% CI 1.09 to 1.21; I2 = 57%); using a single-sided rather than a double-sided questionnaire (OR 1.13; 95% CI 1.02 to 1.25); using stamped return envelopes rather than franked return envelopes (OR 1.23; 95% CI 1.13 to 1.33; I2 = 69%), assuring confidentiality (OR 1.33; 95% CI 1.24 to 1.42); using first-class outward mailing (OR 1.11; 95% CI 1.02 to 1.21); and when questionnaires originated from a university (OR 1.32; 95% CI 1.13 to 1.54). The odds of response were reduced when the questionnaire included questions of a sensitive nature (OR 0.94; 95% CI 0.88 to 1.00). Electronic We found 88 eligible trials that evaluated over 30 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response tripled when: using a brief letter rather than a detailed letter (OR 3.26; 95% CI 1.79 to 5.94); and when a picture was included in an email (OR 3.05; 95% CI 1.84 to 5.06; I2 = 19%). The odds of response almost doubled when: using monetary incentives (OR 1.88; 95% CI 1.31 to 2.71; I2 = 79%); and using a more interesting topic (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by half when: using non-monetary incentives (OR 1.60; 95% CI 1.25 to 2.05); using shorter e-questionnaires (OR 1.51; 95% CI 1.06 to 2.16; I2 = 94%); and using a more interesting e-questionnaire (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third when: offering survey results as an incentive (OR 1.36; 95% CI 1.16 to 1.59); using a white background (OR 1.31; 95% CI 1.10 to 1.56); and when stressing the benefits to society of response (OR 1.38; 95% CI 1.07 to 1.78; I2 = 41%). The odds of response also increased with: personalised e-questionnaires (OR 1.24; 95% CI 1.17 to 1.32; I2 = 41%); using a simple header (OR 1.23; 95% CI 1.03 to 1.48); giving a deadline (OR 1.18; 95% CI 1.03 to 1.34); and by giving a longer time estimate for completion (OR 1.25; 95% CI 0.96 to 1.64). The odds of response were reduced when: "Survey" was mentioned in the e-mail subject (OR 0.81; 95% CI 0.67 to 0.97); when the email or the e-questionnaire was from a male investigator, or it included a male signature (OR 0.55; 95% CI 0.38 to 0.80); and by using university sponsorship (OR 0.84; 95%CI 0.69 to 1.01). The odds of response using a postal questionnaire were over twice those using an e-questionnaire (OR 2.33; 95% CI 2.25 to 2.42; I2 = 98%). Response also increased when: providing a choice of response mode (electronic or postal) rather than electronic only (OR 1.76 95% CI 1.67 to 1.85; I2 = 97%); and when administering the e-questionnaire by computer rather than by smartphone (OR 1.62 95% CI 1.36 to 1.94). AUTHORS' CONCLUSIONS: Researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this Cochrane review.

Compression stockings for preventing deep vein thrombosis in airline passengers.

BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. This is an update of the review first published in 2006. OBJECTIVES: To assess the effects of wearing compression stockings versus not wearing them for preventing DVT in people travelling on flights lasting at least four hours. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 April 2020. We also checked the bibliographies of relevant studies and reviews identified by the search to check for any additional trials. SELECTION CRITERIA: Randomised trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. We sought additional information from trialists where necessary. MAIN RESULTS: One new study that fulfilled the inclusion criteria was identified for this update. Twelve randomised trials (n = 2918) were included in this review: ten (n = 2833) compared wearing graduated compression stockings on both legs versus not wearing them; one trial (n = 50) compared wearing graduated compression tights versus not wearing them; and one trial (n = 35) compared wearing a graduated compression stocking on one leg for the outbound flight and on the other leg on the return flight. Eight trials included people judged to be at low or medium risk of developing DVT (n = 1598) and two included high-risk participants (n = 1273). All flights had a duration of more than five hours. Fifty of 2637 participants with follow-up data available in the trials of wearing compression stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio (OR) 0.10, 95% confidence interval (CI) 0.04 to 0.25, P < 0.001; high-certainty evidence). There were no symptomless DVTs in three trials. Sixteen of 1804 people developed superficial vein thrombosis, four wore stockings, 12 did not (OR 0.45, 95% CI 0.18 to 1.13, P = 0.09; moderate-certainty evidence). No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (mean difference (MD) -4.72, 95% CI -4.91 to -4.52; based on six trials; low-certainty evidence). A further three trials showed reduced oedema in the stockings group but could not be included in the meta-analysis as they used different methods to measure oedema. No significant adverse effects were reported. AUTHORS' CONCLUSIONS: There is high-certainty evidence that airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and low-certainty evidence that leg oedema is reduced if they wear compression stockings. The certainty of the evidence was limited by the way that oedema was measured. There is moderate-certainty evidence that superficial vein thrombosis may be reduced if passengers wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolism or symptomatic DVT because no such events occurred in these trials. Randomised trials to assess these outcomes would need to include a very large number of people.

Oral hygiene interventions for people with intellectual disabilities.

BACKGROUND: Periodontal (gum) disease and dental caries (tooth decay) are the most common causes of tooth loss; dental plaque plays a major role in the development of these diseases. Effective oral hygiene involves removing dental plaque, for example, by regular toothbrushing. People with intellectual disabilities (ID) can have poor oral hygiene and oral health outcomes. OBJECTIVES: To assess the effects (benefits and harms) of oral hygiene interventions, specifically the mechanical removal of plaque, for people with intellectual disabilities (ID). SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases to 4 February 2019: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Register of Studies), MEDLINE Ovid, Embase Ovid and PsycINFO Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. The Embase search was restricted by date due to the Cochrane Centralised Search Project, which makes available clinical trials indexed in Embase through CENTRAL. We handsearched specialist conference abstracts from the International Association of Disability and Oral Health (2006 to 2016). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and some types of non-randomised studies (NRS) (non-RCTs, controlled before-after studies, interrupted time series studies and repeated measures studies) that evaluated oral hygiene interventions targeted at people with ID or their carers, or both. We used the definition of ID in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). We defined oral hygiene as the mechanical removal of plaque. We excluded studies that evaluated chemical removal of plaque, or mechanical and chemical removal of plaque combined. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened search records, identified relevant studies, extracted data, assessed risk of bias and judged the certainty of the evidence according to GRADE criteria. We contacted study authors for additional information if required. We reported RCTs and NRSs separately. MAIN RESULTS: We included 19 RCTs and 15 NRSs involving 1795 adults and children with ID and 354 carers. Interventions evaluated were: special manual toothbrushes, electric toothbrushes, oral hygiene training, scheduled dental visits plus supervised toothbrushing, discussion of clinical photographs showing plaque, varied frequency of toothbrushing, plaque-disclosing agents and individualised care plans. We categorised results as short (six weeks or less), medium (between six weeks and 12 months) and long term (more than 12 months).Most studies were small; all were at overall high or unclear risk of bias. None of the studies reported quality of life or dental caries. We present below the evidence available from RCTs (or NRS if the comparison had no RCTs) for gingival health (inflammation and plaque) and adverse effects, as well as knowledge and behaviour outcomes for the training studies.Very low-certainty evidence suggested a special manual toothbrush (the Superbrush) reduced gingival inflammation (GI), and possibly plaque, more than a conventional toothbrush in the medium term (GI: mean difference (MD) -12.40, 95% CI -24.31 to -0.49; plaque: MD -0.44, 95% CI -0.93 to 0.05; 1 RCT, 18 participants); brushing was carried out by the carers. In the short term, neither toothbrush showed superiority (GI: MD -0.10, 95% CI -0.77 to 0.57; plaque: MD 0.20, 95% CI -0.45 to 0.85; 1 RCT, 25 participants; low- to very low-certainty evidence).Moderate- and low-certainty evidence found no difference between electric and manual toothbrushes for reducing GI or plaque, respectively, in the medium term (GI: MD 0.02, 95% CI -0.06 to 0.09; plaque: standardised mean difference 0.29, 95% CI -0.07 to 0.65; 2 RCTs, 120 participants). Short-term findings were inconsistent (4 RCTs; low- to very low-certainty evidence).Low-certainty evidence suggested training carers in oral hygiene care had no detectable effect on levels of GI or plaque in the medium term (GI: MD -0.09, 95% CI -0.63 to 0.45; plaque: MD -0.07, 95% CI -0.26 to 0.13; 2 RCTs, 99 participants). Low-certainty evidence suggested oral hygiene knowledge of carers was better in the medium term after training (MD 0.69, 95% CI 0.31 to 1.06; 2 RCTs, 189 participants); this was not found in the short term, and results for changes in behaviour, attitude and self-efficacy were mixed.One RCT (10 participants) found that training people with ID in oral hygiene care reduced plaque but not GI in the short term (GI: MD -0.28, 95% CI -0.90 to 0.34; plaque: MD -0.47, 95% CI -0.92 to -0.02; very low-certainty evidence).One RCT (304 participants) found that scheduled dental recall visits (at 1-, 3- or 6-month intervals) plus supervised daily toothbrushing were more likely than usual care to reduce GI (pocketing but not bleeding) and plaque in the long term (low-certainty evidence).One RCT (29 participants) found that motivating people with ID about oral hygiene by discussing photographs of their teeth with plaque highlighted by a plaque-disclosing agent, did not reduce plaque in the medium term (very low-certainty evidence).One RCT (80 participants) found daily toothbrushing by dental students was more effective for reducing plaque in people with ID than once- or twice-weekly toothbrushing in the short term (low-certainty evidence).A benefit to gingival health was found by one NRS that evaluated toothpaste with a plaque-disclosing agent and one that evaluated individualised oral care plans (very low-certainty evidence).Most studies did not report adverse effects; of those that did, only one study considered them as a formal outcome. Some studies reported participant difficulties using the electric or special manual toothbrushes. AUTHORS' CONCLUSIONS: Although some oral hygiene interventions for people with ID show benefits, the clinical importance of these benefits is unclear. The evidence is mainly low or very low certainty. Moderate-certainty evidence was available for only one finding: electric and manual toothbrushes were similarly effective for reducing gingival inflammation in people with ID in the medium term. Larger, higher-quality RCTs are recommended to endorse or refute the findings of this review. In the meantime, oral hygiene care and advice should be based on professional expertise and the needs and preferences of the individual with ID and their carers.

Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Around 30% of people who are admitted to hospital with aneurysmal subarachnoid haemorrhage (SAH) will rebleed in the initial month after the haemorrhage if the aneurysm is not treated. The two most commonly used methods to occlude the aneurysm for prevention of rebleeding are microsurgical clipping of the neck of the aneurysm and occlusion of the lumen of the aneurysm by means of endovascular coiling. This is an update of a systematic review that was previously published in 2005. OBJECTIVES: To compare the effects of endovascular coiling versus neurosurgical clipping in people with aneurysmal SAH on poor outcome, rebleeding, neurological deficit, and treatment complications. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (March 2018). In addition, we searched CENTRAL (2018, Issue 2), MEDLINE (1966 to March 2018), Embase (1980 to March 2018), US National Institutes of Health Ongoing Trials Register (March 2018), and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (last searched March 2018). We also contacted trialists. SELECTION CRITERIA: We included randomised trials comparing endovascular coiling with neurosurgical clipping in people with SAH from a ruptured aneurysm. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, and assessed trial quality and risk of bias using the GRADE approach. We contacted trialists to obtain missing information. We defined poor outcome as death or dependence in daily activities (modified Rankin scale 3 to 6 or Glasgow Outcome Scale (GOS) 1 to 3). In the special worst-case scenario analysis, we assumed all participants in the group with better outcome with missing follow-up information had a poor outcome and those in the other group with missing data a good outcome. MAIN RESULTS: We included four randomised trials involving 2458 participants (range per trial: 20 to 2143 participants). Evidence is mostly based on the largest trial. Most participants were in good clinical condition and had an aneurysm on the anterior circulation. None of the included trials was at low risk of bias in all domains. One trial was at unclear risk in one domain, two trials at unclear risk in three domains, and one trial at high risk in one domain.After one year of follow-up, 24% of participants randomised to endovascular treatment and 32% of participants randomised to the surgical treatment group had poor functional outcome. The risk ratio (RR) of poor outcome (death or dependency) for endovascular coiling versus neurosurgical clipping was 0.77 (95% confidence interval (CI) 0.67 to 0.87; 4 trials, 2429 participants, moderate-quality evidence), and the absolute risk reduction was 7% (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome, the RR for endovascular coiling versus neurosurgical clipping was 0.80 (95% CI 0.71 to 0.91), and the absolute risk reduction was 6% (95% CI 2% to 10%). The RR of death at 12 months was 0.80 (95% CI 0.63 to 1.02; 4 trials, 2429 participants, moderate-quality evidence). In a subgroup analysis of participants with an anterior circulation aneurysm, the RR of poor outcome was 0.78 (95% CI 0.68 to 0.90; 2 trials, 2157 participants, moderate-quality evidence), and the absolute risk decrease was 7% (95% CI 3% to 10%). In subgroup analysis of those with a posterior circulation aneurysm, the RR was 0.41 (95% CI 0.19 to 0.92; 2 trials, 69 participants, low-quality evidence), and the absolute decrease in risk was 27% (95% CI 6% to 48%). At five years, 28% of participants randomised to endovascular treatment and 32% of participants randomised to surgical treatment had poor functional outcome. The RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.87 (95% CI 0.75 to 1.01, 1 trial, 1724 participants, low-quality evidence). At 10 years, 35% participants allocated to endovascular and 43% participants allocated to surgical treatment had poor functional outcome. At 10 years RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.81 (95% CI 0.70 to 0.92; 1 trial, 1316 participants, low-quality evidence). The RR of delayed cerebral ischaemia at two to three months for endovascular coiling versus neurosurgical clipping was 0.84 (95% CI 0.74 to 0.96; 4 trials, 2450 participants, moderate-quality evidence). The RR of rebleeding for endovascular coiling versus neurosurgical clipping was 1.83 (95% CI 1.04 to 3.23; 4 trials, 2458 participants, high-quality evidence) at one year, and 2.69 (95% CI 1.50 to 4.81; 1 trial, 1323 participants, low-quality evidence) at 10 years. The RR of complications from intervention for endovascular coiling versus neurosurgical clipping was 1.05 (95% CI 0.44 to 2.53; 2 trials, 129 participants, low-quality evidence). AUTHORS' CONCLUSIONS: The evidence in this systematic review comes mainly from one large trial, and long-term follow-up is available only for a subgroup of participants within that trial. For people in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation the data from randomised trials show that, if the aneurysm is considered suitable for both neurosurgical clipping and endovascular coiling, coiling is associated with a better outcome. There is no reliable trial evidence that can be used directly to guide treatment in people with a poor clinical condition.

Pharmacological treatment for antipsychotic-related constipation.

BACKGROUND: Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population. An understanding of the effectiveness and safety of treatment for antipsychotic-related constipation is important for clinicians and patients alike. OBJECTIVES: To evaluate the effectiveness and safety of pharmacologic treatment (versus placebo or compared against another treatment) for antipsychotic-related constipation (defined as constipated patients of any age, who are treated with antipsychotics, regardless of dose, in which constipation is considered to be an antipsychotic-related side effect). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (15 June 2015), which is based on regular searches of MEDLINE, Embase, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records in this register. We also handsearched bibliographies and contacted relevant authors for additional information. SELECTION CRITERIA: We included all published and unpublished randomised controlled trials (RCTs) investigating the efficacy of pharmacological treatments in patients with antipsychotic-related constipation. Pharmacological treatments included laxatives and other medicines that could reasonably be used to combat constipation in this population (e.g. anticholinergic agents, like bethanecol). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all included studies and assessed trials for risk of bias. A third author reviewed 20% of trials. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. We discussed any disagreement, documented decisions, and attempted to contact study authors when necessary. MAIN RESULTS: We identified two relevant Chinese studies (N = 480) that contributed data to this review. Both studies were over ten years old and poorly reported, lacking descriptions of contemporary CONSORT reporting prerequisites, such as sequence generation, allocation concealment, blinding, participant flow, how the sample size was determined, or how outcomes were measured. The studies also did not report trial registration, pre-specified protocols, consent processes, ethical review, or funding source. We were unsuccessful in making contact with the authors to clarify the missing details. We classified both studies as having an overall high risk of bias.One study compared glycerol suppository with the traditional Chinese medicine (TCM) approaches of tuina massage and acupuncture. Compared to tuina massage, glycerol laxative was less effective in relieving constipation at both two days after treatment (1 RCT; N = 120; RR 2.88, 95% CI 1.89 to 4.39; very low-quality evidence), and three days (1 RCT; N = 120; RR 4.80, CI 1.96 to 11.74, very low-quality evidence). Favourable results were also seen for acupuncture at two days (1 RCT; N = 120; RR 3.50; 95% CI 2.18 to 5.62; very low-quality evidence), and at three days (1 RCT; N = 120; RR 8.00, 95% CI 2.54 to 25.16; very low-quality evidence).The other study compared mannitol, an osmotic laxative, with rhubarb soda or phenolphthalein. Mannitol was more effective than rhubarb soda or phenolphthalein in trelieving constipation within 24 hours of treatment (1 RCT; N = 240; RR 0.07; 95% CI 0.02 to 0.27, very low-quality evidence).No data were reported for our other important outcomes: need for rescue medication, bowel obstruction (a complication of antipsychotic-related constipation), quality of life, adverse events, leaving the study early, and economic costs. AUTHORS' CONCLUSIONS: We had hoped to find clinically useful evidence appraising the relative merits of the interventions routinely used to manage antipsychotic-related constipation, a common and potentially serious adverse effect of the use of these drugs. The results were disappointing. There were no data comparing the common pharmacological interventions for constipation, such as lactulose, polyethylene glycol, stool softeners, lubricant laxatives, or of novel treatments such as linaclotide. Data available were very poor quality and the trials had a high risk of bias. Data from these biased studies suggested that mannitol, an osmotic laxative, was more effective than rhubarb soda and phenolphthalein in relieving constipation, and a two-week course of glycerol suppositories was less effective than the TCM approaches of tuina massage and acupuncture.Overall, there is insufficient trial-based evidence to assess the effectiveness and safety of pharmacological interventions for treating antipsychotic-related constipation, due to limited, poor quality data (few studies with high risk of bias and no meta-analyses). The methodological limitations in the included studies were obvious, and any conclusions based on their results should be made with caution. Methodologically rigorous RCTs evaluating interventions for treating antipsychotic-related constipation are needed.

Admission avoidance hospital at home.

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care, and always for a limited time period. This is the third update of the original review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, two other databases, and two trials registers on 2 March 2016. We checked the reference lists of eligible articles. We sought unpublished studies by contacting providers and researchers who were known to be involved in the field. SELECTION CRITERIA: Randomised controlled trials recruiting participants aged 18 years and over. Studies comparing admission avoidance hospital at home with acute hospital inpatient care. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data, requested individual patient data from trialists, and relied on published data when this was not available. We used the GRADE approach to assess the certainty of the body of evidence for the most important outcomes. MAIN RESULTS: We included 16 randomised controlled trials with a total of 1814 participants; three trials recruited participants with chronic obstructive pulmonary disease, two trials recruited participants recovering from a stroke, six trials recruited participants with an acute medical condition who were mainly elderly, and the remaining trials recruited participants with a mix of conditions. We assessed the majority of the included studies as at low risk of selection, detection, and attrition bias, and unclear for selective reporting and performance bias. Admission avoidance hospital at home probably makes little or no difference on mortality at six months' follow-up (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.60 to 0.99; P = 0.04; I2 = 0%; 912 participants; moderate-certainty evidence), little or no difference on the likelihood of being transferred (or readmitted) to hospital (RR 0.98, 95% CI 0.77 to 1.23; P = 0.84; I2 = 28%; 834 participants; moderate-certainty evidence), and may reduce the likelihood of living in residential care at six months' follow-up (RR 0.35, 95% CI 0.22 to 0.57; P < 0.0001; I2 = 78%; 727 participants; low-certainty evidence). Satisfaction with healthcare received may be improved with admission avoidance hospital at home (646 participants, low-certainty evidence); few studies reported the effect on caregivers. When the costs of informal care were excluded, admission avoidance hospital at home may be less expensive than admission to an acute hospital ward (287 participants, low-certainty evidence); there was variation in the reduction of hospital length of stay, estimates ranged from a mean difference of -8.09 days (95% CI -14.34 to -1.85) in a trial recruiting older people with varied health problems, to a mean increase of 15.90 days (95% CI 8.10 to 23.70) in a study that recruited patients recovering from a stroke. AUTHORS' CONCLUSIONS: Admission avoidance hospital at home, with the option of transfer to hospital, may provide an effective alternative to inpatient care for a select group of elderly patients requiring hospital admission. However, the evidence is limited by the small randomised controlled trials included in the review, which adds a degree of imprecision to the results for the main outcomes.

Compression stockings for preventing deep vein thrombosis in airline passengers.

BACKGROUND: Air travel might increase the risk of deep vein thrombosis (DVT). It has been suggested that wearing compression stockings might reduce this risk. This is an update of the review first published in 2006. OBJECTIVES: To assess the effects of wearing compression stockings versus not wearing them for preventing DVT in people travelling on flights lasting at least four hours. SEARCH METHODS: For this update the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (10 February 2016). In addition, the CIS searched the Cochrane Register of Studies (CENTRAL (2016, Issue 1)). SELECTION CRITERIA: Randomised trials of compression stockings versus no stockings in passengers on flights lasting at least four hours. Trials in which passengers wore a stocking on one leg but not the other, or those comparing stockings and another intervention were also eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. We sought additional information from trialists where necessary. MAIN RESULTS: One new study that fulfilled the inclusion criteria was identified for this update. Eleven randomised trials (n = 2906) were included in this review: nine (n = 2821) compared wearing graduated compression stockings on both legs versus not wearing them; one trial (n = 50) compared wearing graduated compression tights versus not wearing them; and one trial (n = 35) compared wearing a graduated compression stocking on one leg for the outbound flight and on the other leg on the return flight. Eight trials included people judged to be at low or medium risk of developing DVT (n = 1598) and two included high-risk participants (n = 1273). All flights had a duration of more than five hours.Fifty of 2637 participants with follow-up data available in the trials of wearing compression stockings on both legs had a symptomless DVT; three wore stockings, 47 did not (odds ratio (OR) 0.10, 95% confidence interval (CI) 0.04 to 0.25, P < 0.001; high-quality evidence). There were no symptomless DVTs in three trials. Sixteen of 1804 people developed superficial vein thrombosis, four wore stockings, 12 did not (OR 0.45, 95% CI 0.18 to 1.13, P = 0.09; moderate-quality evidence). No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema (mean difference (MD) -4.72, 95% CI -4.91 to -4.52; based on six trials; low-quality evidence). A further two trials showed reduced oedema in the stockings group but could not be included in the meta-analysis as they used different methods to measure oedema. No significant adverse effects were reported. AUTHORS' CONCLUSIONS: There is high-quality evidence that airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and low-quality evidence that leg oedema is reduced if they wear compression stockings. Quality was limited by the way that oedema was measured. There is moderate-quality evidence that superficial vein thrombosis may be reduced if passengers wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolism or symptomatic DVT because no such events occurred in these trials. Randomised trials to assess these outcomes would need to include a very large number of people.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment.

BACKGROUND: It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis. OBJECTIVES: To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments). SEARCH METHODS: We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied. DATA COLLECTION AND ANALYSIS: Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes. MAIN RESULTS: Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I(2)= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I(2) = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I(2) = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I(2) = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear. AUTHORS' CONCLUSIONS: Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Interventions to improve the use of systematic reviews in decision-making by health system managers, policy makers and clinicians.

BACKGROUND: Systematic reviews provide a transparent and robust summary of existing research. However, health system managers, national and local policy makers and healthcare professionals can face several obstacles when attempting to utilise this evidence. These include constraints operating within the health system, dealing with a large volume of research evidence and difficulties in adapting evidence from systematic reviews so that it is locally relevant. In an attempt to increase the use of systematic review evidence in decision-making a number of interventions have been developed. These include summaries of systematic review evidence that are designed to improve the accessibility of the findings of systematic reviews (often referred to as information products) and changes to organisational structures, such as employing specialist groups to synthesise the evidence to inform local decision-making. OBJECTIVES: To identify and assess the effects of information products based on the findings of systematic review evidence and organisational supports and processes designed to support the uptake of systematic review evidence by health system managers, policy makers and healthcare professionals. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, and Health Economic Evaluations Database. We also handsearched two journals (Implementation Science and Evidence and Policy), Cochrane Colloquium abstracts, websites of key organisations and reference lists of studies considered for inclusion. Searches were run from 1992 to March 2011 on all databases, an update search to March 2012 was run on MEDLINE only. SELECTION CRITERIA: Randomised controlled trials (RCTs), interrupted time-series (ITS) and controlled before-after studies (CBA) of interventions designed to aid the use of systematic reviews in healthcare decision-making were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed the study quality. We extracted the median value across similar outcomes for each study and reported the range of values for each median value. We calculated the median of the two middlemost values if an even number of outcomes were reported. MAIN RESULTS: We included eight studies evaluating the effectiveness of different interventions designed to support the uptake of systematic review evidence. The overall quality of the evidence was very low to moderate.Two cluster RCTs evaluated the effectiveness of multifaceted interventions, which contained access to systematic reviews relevant to reproductive health, to change obstetric care; the high baseline performance in some of the key clinical indicators limited the findings of these studies. There were no statistically significant effects on clinical practice for all but one of the clinical indicators in selected obstetric units in Thailand (median effect size 4.2%, range -11.2% to 18.2%) and none in Mexico (median effect size 3.5%, range 0.1% to 19.0%). In the second cluster RCT there were no statistically significant differences in selected obstetric units in the UK (median effect RR 0.92; range RR 0.57 to RR 1.10). One RCT evaluated the perceived understanding and ease of use of summary of findings tables in Cochrane Reviews. The median effect of the differences in responses for the acceptability of including summary of findings tables in Cochrane Reviews versus not including them was 16%, range 1% to 28%. One RCT evaluated the effect of an analgesic league table, derived from systematic review evidence, and there was no statistically significant effect on self-reported pain. Only one RCT evaluated an organisational intervention (which included a knowledge broker, access to a repository of systematic reviews and provision of tailored messages), and reported no statistically significant difference in evidence informed programme planning.Three interrupted time series studies evaluated the dissemination of printed bulletins based on evidence from systematic reviews. A statistically significant reduction in the rates of surgery for glue ear in children under 10 years (mean annual decline of -10.1%; 95% CI -7.9 to -12.3) and in children under 15 years (quarterly reduction -0.044; 95% CI -0.080 to -0.011) was reported. The distribution to general practitioners of a bulletin on the treatment of depression was associated with a statistically significant lower prescribing rate each quarter than that predicted by the rates of prescribing observed before the distribution of the bulletin (8.2%; P = 0.005). AUTHORS' CONCLUSIONS: Mass mailing a printed bulletin which summarises systematic review evidence may improve evidence-based practice when there is a single clear message, if the change is relatively simple to accomplish, and there is a growing awareness by users of the evidence that a change in practice is required. If the intention is to develop awareness and knowledge of systematic review evidence, and the skills for implementing this evidence, a multifaceted intervention that addresses each of these aims may be required, though there is insufficient evidence to support this approach.

Electric fans for reducing adverse health impacts in heatwaves.

BACKGROUND: Heatwaves are hot weather events, which breach regional or national thresholds, that last for several days. They are likely to occur with increasing frequency in some parts of the world. The potential consequences were illustrated in Europe in August 2003 when there were an estimated 30,000 excess deaths due to a heatwave. Electric fans might be used with the intention of reducing the adverse health effects of a heatwave. Fans do not cool the ambient air but can be used to draw in cooler air from outside when placed at an open window. The aim of the fans would be to increase heat loss by increasing the efficiency of all normal methods of heat loss, but particularly by evaporation and convection methods. However, it should be noted that increased sweating can lead to dehydration and electrolyte imbalances if these fluids and electrolytes are not replaced quickly enough. Research has also identified important gaps in knowledge about the use of fans, which might lead to their inappropriate use. OBJECTIVES: To determine whether the use of electric fans contributes to, or impedes, heat loss at high ambient temperatures during a heatwave, and to contribute to the evidence base for the public health impacts of heatwaves. SEARCH METHODS: We sought unpublished and published studies that had been published in any language. The review team were able to assess studies reported in English, Chinese, Dutch, French and German; and reports in other languages would have been translated into English as necessary. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, the Indian biomedical literature (IndMED and MedIND) and databases of Chinese literature (Chinese Journal Net and Digital Periodical of WanFang Data). The most recent electronic searches were done in April 2012. We also checked the reference lists of relevant articles and the websites of relevant national and international organisations, and consulted with researchers and policy makers with experience in strategies to manage heatwaves to identify additional studies. The titles and abstracts from each search were checked independently by two review authors. The full text articles that we retrieved were checked independently by at least two authors for their relevance and for references to potentially eligible studies. SELECTION CRITERIA: Randomised trials and other experimental designs, such as interrupted time series and controlled before-and-after studies, comparing the use of electric fans with no fans during a heatwave were eligible for this review. The electric fans could be hand-held (battery operated), portable or mounted on the wall or ceiling, or in a window. We sought interventions delivered to anyone for whom a heatwave was likely to have serious adverse health impacts. This would include people of all ages but with a particular focus on some groups (for example older people). Populations from high-, middle- and low-income countries were eligible for the review. DATA COLLECTION AND ANALYSIS: If we had identified eligible studies, they would have been assessed independently by at least two review authors and data would have been extracted on the characteristics of the study, its participants and interventions, as well as the effects on health outcomes. The primary outcomes were mortality, hospital admission and other contacts with healthcare services. MAIN RESULTS: We did not identify any eligible studies despite the extensive searching and correspondence with several experts in this topic area. We identified retrospective, observational studies, usually with a case-control design, that investigated the association between the use of electric fans and health outcomes, including death. The results of these studies were mixed. Some studies found that the use of fans was associated with better health outcomes, others found the reverse. AUTHORS' CONCLUSIONS: The evidence we identified does not resolve uncertainties about the health effects of electric fans during heatwaves. Therefore, this review does not support or refute the use of electric fans during a heatwave. People making decisions about electric fans should consider the current state of the evidence base, and they might also wish to make themselves aware of local policy or guidelines when making a choice about whether or not to use or supply electric fans. The main implication of this review is that high quality research is needed to resolve the long standing and ongoing uncertainty about the benefits and harms of using electric fans during a heatwave, for example randomised trials comparing the health effects in people with electric fans to those in people without them.

Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.

AIMS: To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. METHODS AND RESULTS: MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction. CONCLUSIONS: Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials.

Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews.

BACKGROUND: Many meta-analyses contain only a small number of studies, which makes it difficult to estimate the extent of between-study heterogeneity. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, and offers advantages over conventional random-effects meta-analysis. To assist in this, we provide empirical evidence on the likely extent of heterogeneity in particular areas of health care. METHODS: Our analyses included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews. We classified each meta-analysis according to the type of outcome, type of intervention comparison and medical specialty. By modelling the study data from all meta-analyses simultaneously, using the log odds ratio scale, we investigated the impact of meta-analysis characteristics on the underlying between-study heterogeneity variance. Predictive distributions were obtained for the heterogeneity expected in future meta-analyses. RESULTS: Between-study heterogeneity variances for meta-analyses in which the outcome was all-cause mortality were found to be on average 17% (95% CI 10-26) of variances for other outcomes. In meta-analyses comparing two active pharmacological interventions, heterogeneity was on average 75% (95% CI 58-95) of variances for non-pharmacological interventions. Meta-analysis size was found to have only a small effect on heterogeneity. Predictive distributions are presented for nine different settings, defined by type of outcome and type of intervention comparison. For example, for a planned meta-analysis comparing a pharmacological intervention against placebo or control with a subjectively measured outcome, the predictive distribution for heterogeneity is a log-normal (-2.13, 1.58(2)) distribution, which has a median value of 0.12. In an example of meta-analysis of six studies, incorporating external evidence led to a smaller heterogeneity estimate and a narrower confidence interval for the combined intervention effect. CONCLUSIONS: Meta-analysis characteristics were strongly associated with the degree of between-study heterogeneity, and predictive distributions for heterogeneity differed substantially across settings. The informative priors provided will be very beneficial in future meta-analyses including few studies.

Treating pneumonia in critical care in the United Kingdom following failure of initial antibiotic: a cost-utility analysis comparing meropenem with piperacillin/tazobactam.

BACKGROUND: Treating patients admitted to critical care with severe pneumonia requires timely intervention with an effective antibiotic. This reduces the risk of dying of pneumonia and minimises complications associated with a prolonged stay in critical care. OBJECTIVE: To compare the cost-effectiveness of meropenem 1 g/8 h with piperacillin/tazobactam 4.5 g/8 h for treating pneumonia in UK critical care. METHODS: A Markov model was built to estimate lifetime costs and quality-adjusted life years (QALYs) of using meropenem versus piperacillin/tazobactam to treat severe pneumonia. Estimates of effectiveness, utility weights and costs were obtained from published sources. Probabilistic sensitivity analysis was conducted to address uncertainty in the model results. RESULTS: Cost of treating a patient with severe pneumonia was estimated as £19,026 with meropenem and £19,978 with piperacillin/tazobactam, respectively. QALYs gained were 4.768 with meropenem and 4.654 with piperacillin/tazobactam. Probabilistic sensitivity analysis showed meropenem to be consistently less costly and more effective than piperacillin/tazobactam. CONCLUSION: The additional efficacy of meropenem translates into more patients surviving critical care and leaving this high-cost service more quickly than if they had been treated with piperacillin/tazobactam. As meropenem is more effective and less expensive than piperacillin/tazobactam at treating patients with severe pneumonia, it is the dominant treatment option.

Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis.

BACKGROUND: Cochrane systematic reviews collate and summarise studies of the effects of healthcare interventions. The characteristics of these reviews and the meta-analyses and individual studies they contain provide insights into the nature of healthcare research and important context for the development of relevant statistical and other methods. METHODS: We classified every meta-analysis with at least two studies in every review in the January 2008 issue of the Cochrane Database of Systematic Reviews (CDSR) according to the medical specialty, the types of interventions being compared and the type of outcome. We provide descriptive statistics for numbers of meta-analyses, numbers of component studies and sample sizes of component studies, broken down by these categories. RESULTS: We included 2321 reviews containing 22,453 meta-analyses, which themselves consist of data from 112,600 individual studies (which may appear in more than one meta-analysis). Meta-analyses in the areas of gynaecology, pregnancy and childbirth (21%), mental health (13%) and respiratory diseases (13%) are well represented in the CDSR. Most meta-analyses address drugs, either with a control or placebo group (37%) or in a comparison with another drug (25%). The median number of meta-analyses per review is six (inter-quartile range 3 to 12). The median number of studies included in the meta-analyses with at least two studies is three (inter-quartile range 2 to 6). Sample sizes of individual studies range from 2 to 1,242,071, with a median of 91 participants. DISCUSSION: It is clear that the numbers of studies eligible for meta-analyses are typically very small for all medical areas, outcomes and interventions covered by Cochrane reviews. This highlights the particular importance of suitable methods for the meta-analysis of small data sets. There was little variation in number of studies per meta-analysis across medical areas, across outcome data types or across types of interventions being compared.

Serotonin receptor antagonists for highly emetogenic chemotherapy in adults.

BACKGROUND: Serotonin receptor antagonists (5-HT(3) RAs) are used to control chemotherapy-induced emesis. Although they have the same general mechanism of action (blockade of serotonin receptors), they have different chemical structures and may have different effects. OBJECTIVES: To compare efficacy of different serotonin receptor antagonists (5-HT(3) RAs) in the control of acute and delayed emesis induced by highly emetogenic chemotherapy. SEARCH STRATEGY: We searched CENTRAL, the Specialised Register of the Cochrane PaPaS Group, PubMed, EMBASE, and LILACS databases. Our most recent search was in March 2009. SELECTION CRITERIA: Randomised trials comparing 5-HT(3) RAs in an adult cancer population. DATA COLLECTION AND ANALYSIS: We extracted information from the included studies on the control of acute and delayed nausea and vomiting, either as a single or a combined outcome. Where appropriate, we combined the results of similar trials. We carried out sensitivity and subgroup analyses to test the robustness of our findings. MAIN RESULTS: We included 16 randomised trials (7808 participants). Nine of the trials compared granisetron versus ondansetron. No other drug comparison was studied in more than one trial. The meta-analyses of the granisetron versus ondansetron trials found similar results for the two drugs on acute vomiting (eight trials, 4256 participants, odds ratio (OR) 0.89; 95% CI 0.78 to 1.02), acute nausea (seven trials, 4160 participants, OR 0.97; 95% CI 0.85 to 1.10), delayed vomiting (three trials, 1119 participants, OR 1.00; 95% CI 0.74 to 1.34) and delayed nausea (two trials, 1024 participants, OR 0.96; 95% CI 0.75 to 1.24). Granisetron and ondansetron showed similar effects on headache and diarrhoea, with the possible exception of less constipation associated with ondansetron.One study of 1114 participants comparing palonosetron plus dexamethasone versus granisetron plus dexamethasone showed superiority of palonosetron in controlling delayed vomiting (OR 1.45; 95% CI 1.14 to 1.85) and delayed nausea (OR 1.63; 95% CI 1.27 to 2.10). Complete response for delayed nausea and vomiting was also in favour of the combination palonosetron and dexamethasone (OR 1.63; 95% CI 1.29 to 2.07). AUTHORS' CONCLUSIONS: Ondansetron and granisetron appear to be equivalent drugs for the prevention of acute and delayed emesis following the use of highly emetogenic chemotherapy.According to one single trial the combination of palonosetron and dexamethasone was superior to granisetron and dexamethasone in controlling delayed emesis. However, more evidence is needed before palonosetron could become the candidate 5-HT(3) RA for the control of delayed emesis induced by highly emetogenic chemotherapy.

Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality. OBJECTIVES: Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials. SELECTION CRITERIA: We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy. DATA COLLECTION AND ANALYSIS: We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint. MAIN RESULTS: A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42). AUTHORS' CONCLUSIONS: ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.