Correction: Bailey et al. Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial. Cancers 2022, 14, 374.

In the original publication [...].

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial.

PURPOSE: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). MATERIALS AND METHODS: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. RESULTS: One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). CONCLUSION: The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era.

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial.

BACKGROUND: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. METHODS: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. FINDINGS: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment-time interactions were -0·09 (95% CI -0·19 to 0·00) for namilumab and 0·06 (-0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. INTERPRETATION: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation-as measured by CRP concentration-in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. FUNDING: Medical Research Council.

Protocol for a randomised controlled trial of Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS).

INTRODUCTION: Shoulder pain due to irreparable rotator cuff tears can cause substantial disability, but treatment options are limited. A balloon spacer is a relatively simple addition to a standard arthroscopic debridement procedure, but it is costly and there is no current randomised trial evidence to support its use. This trial will evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for individuals undergoing arthroscopic debridement for irreparable rotator cuff tears.New surgical procedures can provide substantial benefit to patients. Good quality randomised controlled trials (RCTs) are needed, but trials in surgery are typically long and expensive, exposing patients to risk and the healthcare system to substantial costs. One way to improve the efficiency of trials is with an adaptive sample size. Such methods are well established in drug trials but have rarely, if ever, been used in surgical trials. METHODS AND ANALYSIS: Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) is a participant and assessor blinded, adaptive, multicentre RCT comparing arthroscopic debridement with the InSpace balloon (Stryker, USA) to arthroscopic debridement alone for people with a symptomatic irreparable rotator cuff tear. It uses a group sequential adaptive design where interim analyses are performed using all of the 3, 6 and 12-month data that are available at each time point. A maximum of 221 participants will be randomised (1:1 ratio), this will provide 90% power (at the 5% level) for a 6 point difference in the primary outcome; the Oxford Shoulder Score at 12 months. A substudy will use deltoid-active MRI scans in 56 participants to assess the function of the balloon. Analysis will be on an intention-to-treat basis and reported according to principles established in the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: NRES number 18/WM/0025. The results will be disseminated via peer-reviewed publications, presentations at conferences, lay summaries and social media. TRIAL REGISTRATION NUMBER: ISRCTN17825590.

Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes.

We report a case of hypersensitivity pneumonitis (HP) in a young person secondary to vaping. He presented with a putative diagnosis of asthma and required extracorporeal membrane oxygenationbecause of intractable respiratory failure. He developed a critical illness and steroid myopathy and required prolonged rehabilitation. Our patient fulfils diagnostic criteria for HP secondary to e-cigarettes with a positive exposure history, deterioration after skin prick testing, specific serum IgM antibodies against the implicated liquid raising the possibility that the relevant antigen was present in that liquid and radiological and histopathological features compatible with acute HP. There are two learning points. The first is always to consider a reaction to e-cigarettes in someone presenting with an atypical respiratory illness. The second is that we consider e-cigarettes as 'much safer than tobacco' at our peril.

Perioperative haemodynamic therapy for major gastrointestinal surgery: the effect of a Bayesian approach to interpreting the findings of a randomised controlled trial.

OBJECTIVE: The traditional approach of null hypothesis testing dominates the design and analysis of randomised controlled trials. This study aimed to demonstrate how a simple Bayesian analysis could have been used to analyse the Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome (OPTIMISE) trial to obtain more clinically interpretable results. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The OPTIMISE trial was a pragmatic, multicentre, observer-blinded, randomised controlled trial of 734 high-risk patients undergoing major gastrointestinal surgery in 17 acute care hospitals in the UK. Patients were randomly allocated to a cardiac output-guided haemodynamic therapy algorithm for intravenous fluid and inotropic drug administration during and in the 6 hours following surgery (n=368) or to standard care (n=366). The primary outcome was a binary outcome consisting of a composite of predefined 30-day moderate or major complications and mortality. METHODS: We repeated the primary outcome analysis of the OPTIMISE trial using Bayesian statistical methods to calculate the probability that the intervention was superior, and the probability that a clinically relevant difference existed. We explored the impact of a flat prior and an evidence-based prior on our analyses. RESULTS: Although OPTIMISE was not powered to detect a statistically significant difference between the treatment arms for the observed effect size (relative risk=0.84, 95% CI 0.70 to 1.01; p=0.07), by using Bayesian analyses we were able to demonstrate that there was a 96.9% (flat prior) to 99.5% (evidence-based prior) probability that the intervention was superior to the control. CONCLUSIONS: The use of a Bayesian analytical approach provided a different interpretation of the findings of the OPTIMISE trial (compared with the original frequentist analysis), and suggested patient benefit from the intervention. Incorporation of information from previous studies provided further evidence of a benefit from the intervention. Bayesian analyses can produce results that are more easily interpretable and relevant to clinicians and policy-makers. TRIAL REGISTRATION NUMBER: ISRCTN04386758; Post-results.

Electrical impedance tomography effectively used in a case of paediatric pulmonary Langerhans cell histiocytosis.

A 2-year-old boy with severe pulmonary Langerhans cell histiocytosis presented in extreme respiratory failure. He was intubated and ventilated. Despite maximal support, he deteriorated and needed extremely high ventilator pressures. An electrical impedance tomography monitor was used to inform management. This is a monitoring technique which is not used in children due to the lack of suitable interface devices and a lack of randomised clinical evidence. Despite technical difficulties, a good signal was achieved. This informed management and enabled the selection of a suitable ventilator strategy, facilitating weaning. Electrical impedance tomography is a viable technology for use in paediatric critical respiratory failure. This is a non-invasive and safe technology which adds individual patient information which is not available through any other modalities. We urge equipment manufacturers to develop belts which will allow routine application of this life-saving technology in children.

Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection: A Randomized Clinical Trial.

IMPORTANCE: Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings. OBJECTIVE: To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)-186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program. INTERVENTIONS: The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group. MAIN OUTCOMES AND MEASURES: The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. RESULTS: Among 1,194,147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596,642 in the intervention group; 597,505 in the control group), the images were interpreted in 37,688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10,484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, -0.02% to 0.04% points; recall rate, 24,681 [4.14%] vs 24,894 [4.17%]; difference, -0.03% points; 95% CI, -0.10% to 0.04% points; or rate of reader disagreements, 20,471 [3.43%] vs 20,793 [3.48%]; difference, -0.05% points; 95% CI, -0.11% to 0.02% points). CONCLUSIONS AND RELEVANCE: Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN46603370.

Paravertebral block versus thoracic epidural for patients undergoing thoracotomy.

BACKGROUND: Operations on structures in the chest (usually the lungs) involve cutting between the ribs (thoracotomy). Severe post-thoracotomy pain can result from pleural (lung lining) and muscular damage, costovertebral joint (ribcage) disruption and intercostal nerve (nerves that run along the ribs) damage during surgery. Poor pain relief after surgery can impede recovery and increase the risks of developing complications such as lung collapse, chest infections and blood clots due to ineffective breathing and clearing of secretions. Effective management of acute pain following thoracotomy may prevent these complications and reduce the likelihood of developing chronic pain. A multi-modal approach to analgesia is widely employed by thoracic anaesthetists using a combination of regional anaesthetic blockade and systemic analgesia, with both non-opioid and opioid medications and local anaesthesia blockade.There is some evidence that blocking the nerves as they emerge from the spinal column (paravertebral block, PVB) may be associated with a lower risk of major complications in thoracic surgery but the majority of thoracic anaesthetists still prefer to use a thoracic epidural blockade (TEB) as analgesia for their patients undergoing thoracotomy. In order to bring about a change in practice, anaesthetists need a review that evaluates the risk of all major complications associated with thoracic epidural and paravertebral block in thoracotomy. OBJECTIVES: To compare the two regional techniques of TEB and PVB in adults undergoing elective thoracotomy with respect to:1. analgesic efficacy;2. the incidence of major complications (including mortality);3. the incidence of minor complications;4. length of hospital stay;5. cost effectiveness. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 9); MEDLINE via Ovid (1966 to 16 October 2013); EMBASE via Ovid (1980 to 16 October 2013); CINAHL via EBSCO host (1982 to 16 October 2013); and reference lists of retrieved studies. We handsearched the Journal of Cardiothoracic Surgery and Journal of Cardiothoracic and Vascular Anesthesia (16 October 2013). We reran the search on 31st January 2015. We found one additional study which is awaiting classification and will be addressed when we update the review. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing PVB with TEB in thoracotomy, including upper gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JY and SG) independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta-analysis). MAIN RESULTS: We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real-world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low-quality evidence that showed no significant difference in 30-day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate-quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate-quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs. AUTHORS' CONCLUSIONS: Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30-day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well-conducted, adequately-powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs.

Changing case Order to Optimise patterns of Performance in mammography Screening (CO-OPS): study protocol for a randomized controlled trial.

BACKGROUND: X-ray mammography remains the predominant test for screening for breast cancer, with the aim of reducing breast cancer mortality. In the English NHS Breast Screening Programme each woman's mammograms are examined separately by two expert readers. The two readers read each batch in the same order and each indicates if there should be recall for further tests. This is a highly skilled, pressurised, repetitive and frequently intellectually unchallenging activity where readers examine one or more batches of 30-50 women's mammograms in each session. A vigilance decrement or performance decrease over time has been observed in similar repetitive visual tasks such as radar operation. METHODS/DESIGN: The CO-OPS study is a pragmatic, multi-centre, two-arm, double blind cluster randomised controlled trial of a computer software intervention designed to reduce the effects of a vigilance decrement in breast cancer screening. The unit of randomisation is the batch. Intervention batches will be examined in the opposite order by the two readers (one forwards, one backwards). Control batches will be read in the same order as one another, as is current standard practice. The hypothesis is that cancer detection rates will be higher in the intervention group because each readers' peak performance will occur when examining different women's mammograms. The trial will take place in 44 English breast screening centres for 1 year and 4 months. The primary outcome is cancer detection rate, which will be extracted from computer records after 1 year of the trial. The secondary outcomes include rate of disagreement between readers (a more statistically powerful surrogate for cancer detection rate), recall rate, positive predictive value, and interval cancer rate (cancers found between screening rounds which will be measured three years after the end of the trial). DISCUSSION: This is the first trial of an intervention to ameliorate a vigilance decrement in breast cancer screening. TRIAL REGISTRATION: ISRCTN46603370 (submitted: 24 October 2012, date of registration: 26 March 2013).

The beta agonist lung injury trial prevention. A randomized controlled trial.

RATIONALE: Experimental studies suggest that pretreatment with ß-agonists might prevent acute lung injury (ALI). OBJECTIVES: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled ß-agonists effects the development of early ALI. METHODS: We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 µg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury. MEASUREMENTS AND MAIN RESULTS: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life. Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury. CONCLUSION: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI. Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).

Interventions for preventing falls in older people living in the community.

BACKGROUND: Approximately 30% of people over 65 years of age living in the community fall each year. This is an update of a Cochrane review first published in 2009. OBJECTIVES: To assess the effects of interventions designed to reduce the incidence of falls in older people living in the community. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (February 2012), CENTRAL (The Cochrane Library 2012, Issue 3), MEDLINE (1946 to March 2012), EMBASE (1947 to March 2012), CINAHL (1982 to February 2012), and online trial registers. SELECTION CRITERIA: Randomised trials of interventions to reduce falls in community-dwelling older people. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. We used a rate ratio (RaR) and 95% confidence interval (CI) to compare the rate of falls (e.g. falls per person year) between intervention and control groups. For risk of falling, we used a risk ratio (RR) and 95% CI based on the number of people falling (fallers) in each group. We pooled data where appropriate. MAIN RESULTS: We included 159 trials with 79,193 participants. Most trials compared a fall prevention intervention with no intervention or an intervention not expected to reduce falls. The most common interventions tested were exercise as a single intervention (59 trials) and multifactorial programmes (40 trials). Sixty-two per cent (99/159) of trials were at low risk of bias for sequence generation, 60% for attrition bias for falls (66/110), 73% for attrition bias for fallers (96/131), and only 38% (60/159) for allocation concealment.Multiple-component group exercise significantly reduced rate of falls (RaR 0.71, 95% CI 0.63 to 0.82; 16 trials; 3622 participants) and risk of falling (RR 0.85, 95% CI 0.76 to 0.96; 22 trials; 5333 participants), as did multiple-component home-based exercise (RaR 0.68, 95% CI 0.58 to 0.80; seven trials; 951 participants and RR 0.78, 95% CI 0.64 to 0.94; six trials; 714 participants). For Tai Chi, the reduction in rate of falls bordered on statistical significance (RaR 0.72, 95% CI 0.52 to 1.00; five trials; 1563 participants) but Tai Chi did significantly reduce risk of falling (RR 0.71, 95% CI 0.57 to 0.87; six trials; 1625 participants).Multifactorial interventions, which include individual risk assessment, reduced rate of falls (RaR 0.76, 95% CI 0.67 to 0.86; 19 trials; 9503 participants), but not risk of falling (RR 0.93, 95% CI 0.86 to 1.02; 34 trials; 13,617 participants).Overall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.Home safety assessment and modification interventions were effective in reducing rate of falls (RR 0.81, 95% CI 0.68 to 0.97; six trials; 4208 participants) and risk of falling (RR 0.88, 95% CI 0.80 to 0.96; seven trials; 4051 participants). These interventions were more effective in people at higher risk of falling, including those with severe visual impairment. Home safety interventions appear to be more effective when delivered by an occupational therapist.An intervention to treat vision problems (616 participants) resulted in a significant increase in the rate of falls (RaR 1.57, 95% CI 1.19 to 2.06) and risk of falling (RR 1.54, 95% CI 1.24 to 1.91). When regular wearers of multifocal glasses (597 participants) were given single lens glasses, all falls and outside falls were significantly reduced in the subgroup that regularly took part in outside activities. Conversely, there was a significant increase in outside falls in intervention group participants who took part in little outside activity.Pacemakers reduced rate of falls in people with carotid sinus hypersensitivity (RaR 0.73, 95% CI 0.57 to 0.93; three trials; 349 participants) but not risk of falling. First eye cataract surgery in women reduced rate of falls (RaR 0.66, 95% CI 0.45 to 0.95; one trial; 306 participants), but second eye cataract surgery did not.Gradual withdrawal of psychotropic medication reduced rate of falls (RaR 0.34, 95% CI 0.16 to 0.73; one trial; 93 participants), but not risk of falling. A prescribing modification programme for primary care physicians significantly reduced risk of falling (RR 0.61, 95% CI 0.41 to 0.91; one trial; 659 participants).An anti-slip shoe device reduced rate of falls in icy conditions (RaR 0.42, 95% CI 0.22 to 0.78; one trial; 109 participants). One trial (305 participants) comparing multifaceted podiatry including foot and ankle exercises with standard podiatry in people with disabling foot pain significantly reduced the rate of falls (RaR 0.64, 95% CI 0.45 to 0.91) but not the risk of falling.There is no evidence of effect for cognitive behavioural interventions on rate of falls (RaR 1.00, 95% CI 0.37 to 2.72; one trial; 120 participants) or risk of falling (RR 1.11, 95% CI 0.80 to 1.54; two trials; 350 participants).Trials testing interventions to increase knowledge/educate about fall prevention alone did not significantly reduce the rate of falls (RaR 0.33, 95% CI 0.09 to 1.20; one trial; 45 participants) or risk of falling (RR 0.88, 95% CI 0.75 to 1.03; four trials; 2555 participants).No conclusions can be drawn from the 47 trials reporting fall-related fractures.Thirteen trials provided a comprehensive economic evaluation. Three of these indicated cost savings for their interventions during the trial period: home-based exercise in over 80-year-olds, home safety assessment and modification in those with a previous fall, and one multifactorial programme targeting eight specific risk factors. AUTHORS' CONCLUSIONS: Group and home-based exercise programmes, and home safety interventions reduce rate of falls and risk of falling.Multifactorial assessment and intervention programmes reduce rate of falls but not risk of falling; Tai Chi reduces risk of falling.Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment.

Interventions for preventing falls in older people living in the community.

BACKGROUND: Approximately 30% of people over 65 years of age living in the community fall each year. OBJECTIVES: To assess the effects of interventions to reduce the incidence of falls in older people living in the community. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE, EMBASE, CINAHL, and Current Controlled Trials (all to May 2008). SELECTION CRITERIA: Randomised trials of interventions to reduce falls in community-dwelling older people. Primary outcomes were rate of falls and risk of falling. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Data were pooled where appropriate. MAIN RESULTS: We included 111 trials (55,303 participants).Multiple-component group exercise reduced rate of falls and risk of falling (rate ratio (RaR) 0.78, 95%CI 0.71 to 0.86; risk ratio (RR) 0.83, 95%CI 0.72 to 0.97), as did Tai Chi (RaR 0.63, 95%CI 0.52 to 0.78; RR 0.65, 95%CI 0.51 to 0.82), and individually prescribed multiple-component home-based exercise (RaR 0.66, 95%CI 0.53 to 0.82; RR 0.77, 95%CI 0.61 to 0.97).Assessment and multifactorial intervention reduced rate of falls (RaR 0.75, 95%CI 0.65 to 0.86), but not risk of falling.Overall, vitamin D did not reduce falls (RaR 0.95, 95%CI 0.80 to 1.14; RR 0.96, 95%CI 0.92 to 1.01), but may do so in people with lower vitamin D levels. Overall, home safety interventions did not reduce falls (RaR 0.90, 95%CI 0.79 to 1.03); RR 0.89, 95%CI 0.80 to 1.00), but were effective in people with severe visual impairment, and in others at higher risk of falling. An anti-slip shoe device reduced rate of falls in icy conditions (RaR 0.42, 95%CI 0.22 to 0.78).Gradual withdrawal of psychotropic medication reduced rate of falls (RaR 0.34, 95%CI 0.16 to 0.73), but not risk of falling. A prescribing modification programme for primary care physicians significantly reduced risk of falling (RR 0.61, 95%CI 0.41 to 0.91).Pacemakers reduced rate of falls in people with carotid sinus hypersensitivity (RaR 0.42, 95%CI 0.23 to 0.75). First eye cataract surgery reduced rate of falls (RaR 0.66, 95%CI 0.45 to 0.95).There is some evidence that falls prevention strategies can be cost saving. AUTHORS' CONCLUSIONS: Exercise interventions reduce risk and rate of falls. Research is needed to confirm the contexts in which multifactorial assessment and intervention, home safety interventions, vitamin D supplementation, and other interventions are effective.