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© 2023 European Academy of Neurology, Hariz and colleagues [1] argue that the new EAN/MDS GL contradicts the repeated endorsements of pallidotomy by the MDS. The MDS has previously published “evidence based medicine (EBM) reviews,” which appraise each treatment on the basis of welldefined criteria but are not GLs. Clinical GLs, such as the new EAN/MDS GL, also take into consideration other variables, including context, summarizing the current medical knowledge, weighing the benefits and harms of treatments, and giving specific recommendations based on this information. The specific GRADE GL methodology allows for the evaluation of available scientific evidence with a sophisticated evaluation process that includes grading the strength of the evidence and the certainty of that evidence, out of which the recommendations are developed. These steps are well documented in our appendices 1 and 2 for methodology and appendices 3 and 4 for outcomes. Thus, the case of radiofrequency pallidotomy and deep brain stimulation (DBS) of the pallidum, which is discussed by Hariz et al, illustrates the difference between EBM reviews and GLs. The EBM review ranks pallidotomy at the same level as globus pallidus internus (GPi)-DBS: both treatments are considered “efficacious,” “clinically useful,” and coming with a “clinically acceptable risk with specialized monitoring,” but it does not express whether the treatments are equal in their application in patients overall. In our GL using the GRADE methodology, in contrast, GPi-DBS is recommended, whereas pallidotomy is recommended only with restrictions.

[Background and Purpose] This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist and general practitioners taking care of PD patients should know the therapies and their place in the treatment pathway., [Methods] Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging–guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (intrajejunal levodopa/carbidopa pump [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, clinical consensus of the guideline task force was gathered., [Results] Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson's disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as change compared with current medical treatment. STN-DBS is the best-studied intervention for advanced PD with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. Clinical consensus was reached for the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended., [Conclusions] Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis. They differ in their profile of effects and have been tested only for specific patient groups., The GL development was further supported by travel grants for meetings and support for online meetings by EAN/MDS-ES. Katarzyna Śmiłowska was supported with a stipend of the Medical Faculty of the Christian-Albrechts-University, Kiel. Open Access funding enabled and organized by Projekt DEAL. Mir has received grants from the Spanish Ministry of Science and Innovation, the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional, the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía, and the Consejería de Salud y Bienestar Social de la Junta de Andalucía. A. Schrag has received grants from GE Healthcare.

Background: Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19. Objectives: To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly. Search methods: We searched the Cochrane COVID-19 Study Register and the COVID-19 L-OVE Platform (search date 5 November 2021). These sources are maintained through regular searches of MEDLINE, Embase, CENTRAL, trial registers and other sources. We also checked the World Health Organization International Clinical Trials Registry Platform, regulatory agency websites, Retraction Watch (search date 3 November 2021). Selection criteria: We included randomised controlled trials (RCTs) evaluating IL-1 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. Data collection and analysis: We followed Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two researchers independently screened and extracted data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence using the GRADE approach for the critical outcomes of clinical improvement (Day 28; ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28; ≥ D60); all-cause mortality (D28; ≥ D60); incidence of any adverse events; and incidence of serious adverse events. Main results: We identified four RCTs of anakinra (three published in peer-reviewed journals, one reported as a preprint) and two RCTs of canakinumab (published in peer-reviewed journals). All trials were multicentre (2 to 133 centres). Two trials stopped early (one due to futility and one as the trigger for inferiority was met). The median/mean age range varied from 58 to 68 years; the proportion of men varied from 58% to 77%. All participants were hospitalised; 67% to 100% were on oxygen at baseline but not intubated; between 0% and 33% were intubated at baseline. We identified a further 16 registered trials with no results available, of which 15 assessed anakinra (four completed, four terminated, five ongoing, three not recruiting) and one (completed) trial assessed canakinumab. Effectiveness of anakinra for people with COVID-19. Anakinra probably results in little or no increase in clinical improvement at D28 (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.97 to 1.20; 3 RCTs, 837 participants; absolute effect: 59 more per 1000 (from 22 fewer to 147 more); moderate-certainty evidence. The evidence is uncertain about an effect of anakinra on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.67, 95% CI 0.36 to 1.22; 2 RCTs, 722 participants; absolute effect: 55 fewer per 1000 (from 107 fewer to 37 more); low-certainty evidence) and ≥ D60 (RR 0.54, 95% CI 0.30 to 0.96; 1 RCT, 606 participants; absolute effect: 47 fewer per 1000 (from 72 fewer to 4 fewer) low-certainty evidence); and 2) all-cause mortality at D28 (RR 0.69, 95% CI 0.34 to 1.39; 2 RCTs, 722 participants; absolute effect: 32 fewer per 1000 (from 68 fewer to 40 more); low-certainty evidence). The evidence is very uncertain about an effect of anakinra on 1) the proportion of participants with clinical improvement at ≥ D60 (RR 0.93, 95% CI 0.78 to 1.12; 1 RCT, 115 participants; absolute effect: 59 fewer per 1000 (from 186 fewer to 102 more); very low-certainty evidence); and 2) all-cause mortality at ≥ D60 (RR 1.03, 95% CI 0.68 to 1.56; 4 RCTs, 1633 participants; absolute effect: 8 more per 1000 (from 84 fewer to 147 more); very low-certainty evidence). Safety of anakinra for people with COVID-19. Anakinra probably results in little or no increase in adverse events (RR 1.02, 95% CI 0.94 to 1.11; 2 RCTs, 722 participants; absolute effect: 14 more per 1000 (from 43 fewer to 78 more); moderate-certainty evidence). The evidence is uncertain regarding an effect of anakinra on serious adverse events (RR 0.95, 95% CI 0.58 to 1.56; 2 RCTs, 722 participants; absolute effect: 12 fewer per 1000 (from 104 fewer to 138 more); low-certainty evidence). Effectiveness of canakinumab for people with COVID-19. Canakinumab probably results in little or no increase in clinical improvement at D28 (RR 1.05, 95% CI 0.96 to 1.14; 2 RCTs, 499 participants; absolute effect: 42 more per 1000 (from 33 fewer to 116 more); moderate-certainty evidence). The evidence of an effect of canakinumab is uncertain on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.72, 95% CI 0.44 to 1.20; 2 RCTs, 499 participants; absolute effect: 35 fewer per 1000 (from 69 fewer to 25 more); low-certainty evidence); and 2) all-cause mortality at D28 (RR:0.75; 95% CI 0.39 to 1.42); 2 RCTs, 499 participants; absolute effect: 20 fewer per 1000 (from 48 fewer to 33 more); low-certainty evidence). The evidence is very uncertain about an effect of canakinumab on all-cause mortality at ≥ D60 (RR 0.55, 95% CI 0.16 to 1.91; 1 RCT, 45 participants; absolute effect: 112 fewer per 1000 (from 210 fewer to 227 more); very low-certainty evidence). Safety of canakinumab for people with COVID-19. Canakinumab probably results in little or no increase in adverse events (RR 1.02; 95% CI 0.86 to 1.21; 1 RCT, 454 participants; absolute effect: 11 more per 1000 (from 74 fewer to 111 more); moderate-certainty evidence). The evidence of an effect of canakinumab on serious adverse events is uncertain (RR 0.80, 95% CI 0.57 to 1.13; 2 RCTs, 499 participants; absolute effect: 44 fewer per 1000 (from 94 fewer to 28 more); low-certainty evidence). Authors' conclusions: Overall, we did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated. The findings of this review are updated on the COVID-NMA platform (covid-nma.com).

Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes. We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs). MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available. This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.

Introduction: COVID-19 is a public health emergency all around the world. Severe illness occurred in about 14% of patients and 5% of patients developed critical illness, but the prognosis for these patients remains unclear. Objective: To describe the prognosis in hospitalized adults with COVID-19. Methods: The MEDLINE, EMBASE, AMED, and COCHRANE databases were searched for studies published up to 28 June 2021 without language restrictions. Descriptors were related to “COVID-19” and “prognosis”. Prospective inception cohort studies that assessed morbidity, mortality and recovery in hospitalized people over 18 years old with COVID-19 were included. Two independent reviewers selected eligible studies and extracted the available data. Acute respiratory distress syndrome (ARDS) and multiple organ failure (MOFS) were considered as outcomes for morbidity and discharge was considered for recovery. The Quality in Prognosis Studies (QUIPS) tool was used to assess risk of bias. Analyses were performed using Comprehensive Meta-Analysis (version 2.2.064). Results: We included 30 inception cohort studies investigating 13,717 people hospitalized with COVID-19 from different countries. The mean (SD) age was 60.90 (21.87) years, and there was high proportion of males (76.19%) and people with comorbidities (e.g., 49.44% with hypertension and 29.75% with diabetes). Findings suggested a high occurrence of morbidity, mainly related to ARDS. Morbidity rates varied across studies from 19% to 36% in hospital wards, and from 13% to 90% in Intensive Care Units—ICU. Mortality rates ranged from 4% to 38% in hospital wards and from 8% to 51% in ICU. Recovery rates ranged up to 94% and 65% in hospital wards and ICU, respectively. The included studies had high risk of bias in the confounding domain. Conclusions: The prognosis of people hospitalized with COVID-19 is an issue for the public health system worldwide, with high morbidity and mortality rates, mainly in ICU and for patients with comorbidities. Its prognosis emphasizes the need for appropriate prevention and management strategies.

Corticosteroids are medications with anti-inflammatory and immunosuppressant properties. Systemic corticosteroids administered through the oral, intravenous, or intramuscular routes have been used to treat various types of low back pain, including radicular back pain (not due to spinal stenosis), non-radicular back pain, and spinal stenosis. However, there is uncertainty about the benefits and harms of systemic corticosteroids for low back pain.To evaluate the benefits and harms of systemic corticosteroids versus placebo or no corticosteroid for radicular low back pain, non-radicular low back pain, and symptomatic spinal stenosis in adults.We used standard, extensive Cochrane search methods. The latest search date was September 2021.We included randomized and quasi-randomized trials in adults of systematic corticosteroids versus placebo or no corticosteroid.We used standard Cochrane methods. The major outcomes were pain, function, need for surgery, serious adverse effect, and presence of hyperglycemia. The minor outcomes were quality of life, successful outcomes, non-serious adverse events, and withdrawal due to adverse events. We used GRADE to assess the certainty of evidence for each outcome.Thirteen trials (1047 participants) met the inclusion criteria. Nine trials included participants with radicular low back pain, two trial with low back pain, and two trials with spinal stenosis. All trials blinded participants to receipt of systemic corticosteroids. Seven trials were at low risk of bias, five at unclear risk, and one at high risk of selection bias. Two trials were at high risk of attrition bias. Doses and duration of systemic corticosteroid therapy varied. Radicular low back pain For radicular low back pain, moderate-certainty evidence indicated that systemic corticosteroids probably slightly decrease pain versus placebo at short-term follow-up (mean difference (MD) 0.56 points better, 95% confidence interval (CI) 1.08 to 0.04 on a 0 to 10 scale) and may slightly increase the likelihood of experiencing improvement in pain at short-term follow-up (risk ratio (RR) 1.21, 95% CI 0.88 to 1.66; absolute effect 5% better (95% CI 5% worse to 15% better). Systemic corticosteroids may not improve function at short-term follow-up (standardized mean difference (SMD) 0.14 better; range 0.49 better to 0.21 worse) and probably increase the likelihood of improvement in function at short-term follow-up (RR 1.52, 95% CI 1.22 to 1.91; absolute effect 19% better, 95% CI 8% better to 30% better). Systemic corticosteroids were associated with greater improvement in function versus placebo at long-term follow-up (MD -7.40, 95% CI -12.55 to -2.25 on the 0 to 100 Oswestry Disability Index) and greater likelihood of functional improvement (RR 1.29, 95% CI 1.06 to 1.56), based on a single trial. There was no difference in likelihood of surgery (RR 1.00, 95% CI 0.68 to 1.47). Evidence indicated that systemic corticosteroids (administered as a single dose or as a short course of therapy) are not associated with increased risk of any adverse event, serious adverse events, withdrawal due to adverse events, or hyperglycemia, but estimates were imprecise as some trials did not report harms, and harms reporting was suboptimal in trials that did provide data. Limitations included variability across trials in interventions (e.g. corticosteroid used, dose and duration of treatment), clinical settings, and participants (e.g. duration of symptoms, methods for diagnosis); limited utility of subgroup analyses due to small numbers of trials; methodologic limitations or suboptimal reporting of methods by some trials; and too few trials to formally assess for publication bias using graphical or statistical tests for small sample effects. Non-radicular low back pain Evidence on systemic corticosteroids versus placebo for non-radicular pain was limited and suggested that systemic corticosteroids may be associated with slightly worse short-term pain but slightly better function. Spinal stenosis For spinal stenosis, limited evidence indicated that systemic corticosteroids are probably no more effective than placebo for short-term pain or function.Systemic corticosteroids appear to be slightly effective at improving short-term pain and function in people with radicular low back pain not due to spinal stenosis, and might slightly improve long-term function. The effects of systemic corticosteroids in people with non-radicular low back pain are unclear and systemic corticosteroids are probably ineffective for spinal stenosis. A single dose or short course of systemic corticosteroids for low back pain does not appear to cause serious harms, but evidence is limited.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: We aim to assess population‐level effects of human papillomavirus (HPV) vaccination programmes on HPV‐related disease and harms from vaccination.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: We aim to evaluate the safety and efficacy of WHO pre‐qualified human papillomavirus (HPV) vaccines given in different dose schedules, in females and males, to prevent cervical cancer and other HPV‐related diseases by undertaking a network meta‐analysis (NMA). We will rank the different vaccines and dose schedules according to the critical outcomes.

To determine the frequency of red flag signs and symptoms in patients presenting with back pain to the Emergency Department (ED) and association with serious pathologies and investigations performed. This retrospective observational study evaluated consecutive patients presenting with back pain to a Melbourne ED over a 14-month period. Data regarding red flags, patient characteristics, ED-initiated investigations, and diagnoses were extracted from medical records. Prevalence of each red flag and sensitivity, specificity, and likelihood ratios for diagnosing serious spinal or non-spinal pathology were calculated. Analysis was undertaken on 1000 eligible participants with back pain. 69% had red flags. Participants were categorised into diagnostic groups: musculoskeletal (80.6%), serious spinal (3.3%), and serious non-spinal (14.6%) pathologies. A number of red flags had positive likelihood ratios (LR) > 5, indicating a higher probability of serious pathology (spinal/non-spinal) including fever (LR + 68.8), tuberculosis history (LR + 13.8), known nephrolithiasis/abdominal aortic aneurysm (LR + 10.2), unexplained weight-loss (LR + 9.2), writhing in pain (LR + 6.9), urinary symptoms (LR + 5.4), and flank pain (LR + 5.2). Red flags with positive LR > 5 indicating a higher probability of serious spinal pathology were saddle anaesthesia (LR + 11.0), tuberculosis history (LR + 9.8), intravenous drug-use (LR + 6.9), acute-onset urinary retention (LR + 6.4), and anal tone loss (LR + 6.3). The majority of this study cohort had back pain of benign cause. Some red flags were associated with greater risk of serious pathology, others were not. Further evidence regarding red flags and their association with serious pathology is required, to better inform clinical guidelines.

Background There are a growing number of studies using mediation analysis to understand the mechanisms of health interventions and exposures. Recent work has shown that the reporting of these studies is heterogenous and incomplete. This problem stifles clinical application, reproducibility, and evidence synthesis. This paper describes the processes and methods that will be used to develop a guideline for reporting studies of mediation analyses (AGReMA). Methods/design AGReMA will be developed over five overlapping stages. Stage one will comprise a systematic review to examine relevant evidence on the quality of reporting in published studies that use mediation analysis. In the second stage we will consult a group of methodologists and applied researchers by using a Delphi process to identify items that should be considered for inclusion in AGReMA. The third stage will involve a consensus meeting to consolidate and prioritise key items to be included in AGReMA. The fourth stage will involve the production of AGReMA and an accompanying explanation and elaboration document. In the final stage we will disseminate the AGReMA statement via journals, conferences, and professional meetings across multiple disciplines. Discussion The development and implementation of AGReMA will improve the standardization, transparency, and completeness in the reporting of studies that use mediation analysis to understand the mechanisms of health interventions and exposures.

Protocol for a Cochrane Effective Practice and Organisation of Care (EPOC) review update, Simon Lewin receives additional funding from the South African Medical Research Council

Chronic pain in childhood is an international public health problem. We conducted a systematic review and meta-analysis to provide a summary of the published evidence of pharmacological, physical, and psychological therapies for children with chronic pain conditions. We searched CENTRAL, MEDLINE, EMBASE, and PsycINFO from inception to April 2020; clinical trial registries; and other sources for randomised controlled trials or comparative observational trials. We extracted critical outcomes of pain intensity, quality of life, physical functioning, role functioning, emotional functioning, sleep, and adverse events. We assessed studies for risk of bias and certainty of the evidence using GRADE. We included 34 pharmacological (4091 participants), 25 physical therapy (1470 participants), and 63 psychological trials (5025 participants). Participants reported a range of chronic pain conditions. Most studies were assessed to have unclear or high risk of bias across multiple domains. Pharmacological, physical, and psychological therapies showed some benefit for reducing pain, posttreatment, but only physical and psychological therapies improved physical functioning. We found no benefit of any treatment modality for health-related quality of life, role functioning, emotional functioning, or sleep. Adverse events were poorly reported, particularly for psychological and physical interventions. The largest evidence base for the management of chronic pain in children supports the use of psychological therapies, followed by pharmacological and physical therapies. However, we rated most outcomes as low or very low certainty, meaning further evidence is likely to change our confidence in the estimates of effects. This protocol was registered on PROSPERO (CRD42020172451).

Importance: Mediation analyses of randomized trials and observational studies can generate evidence about the mechanisms by which interventions and exposures may influence health outcomes. Publications of mediation analyses are increasing, but the quality of their reporting is suboptimal. Objective: To develop international, consensus-based guidance for the reporting of mediation analyses of randomized trials and observational studies (A Guideline for Reporting Mediation Analyses; AGReMA). Design, Setting, and Participants: The AGReMA statement was developed using the Enhancing Quality and Transparency of Health Research (EQUATOR) methodological framework for developing reporting guidelines. The guideline development process included (1) an overview of systematic reviews to assess the need for a reporting guideline; (2) review of systematic reviews of relevant evidence on reporting mediation analyses; (3) conducting a Delphi survey with panel members that included methodologists, statisticians, clinical trialists, epidemiologists, psychologists, applied clinical researchers, clinicians, implementation scientists, evidence synthesis experts, representatives from the EQUATOR Network, and journal editors (n = 19; June-November 2019); (4) having a consensus meeting (n = 15; April 28-29, 2020); and (5) conducting a 4-week external review and pilot test that included methodologists and potential users of AGReMA (n = 21; November 2020). Results: A previously reported overview of 54 systematic reviews of mediation studies demonstrated the need for a reporting guideline. Thirty-three potential reporting items were identified from 3 systematic reviews of mediation studies. Over 3 rounds, the Delphi panelists ranked the importance of these items, provided 60 qualitative comments for item refinement and prioritization, and suggested new items for consideration. All items were reviewed during a 2-day consensus meeting and participants agreed on a 25-item AGReMA statement for studies in which mediation analyses are the primary focus and a 9-item short-form AGReMA statement for studies in which mediation analyses are a secondary focus. These checklists were externally reviewed and pilot tested by 21 expert methodologists and potential users, which led to minor adjustments and consolidation of the checklists. Conclusions and Relevance: The AGReMA statement provides recommendations for reporting primary and secondary mediation analyses of randomized trials and observational studies. Improved reporting of studies that use mediation analyses could facilitate peer review and help produce publications that are complete, accurate, transparent, and reproducible.

Introduction Although several non-pharmacological interventions have been tested in the management of Fibromyalgia (FM), there is little consensus regarding the best options for the treatment of this health condition. The purpose of this network meta-analysis (NMA) is to investigate the comparative efficacy and acceptability of non-pharmacological interventions for FM, in order to assist clinical decision making through a ranking of interventions in relation to the most important clinical outcomes in these patients. Methods and analysis We will perform a systematic search to identify randomised controlled trials of non-pharmacological interventions endorsed in guidelines and systematic reviews. Information sources searched will include major bibliographic databases without language or date restrictions (MEDLINE, Cochrane Library, EMBASE, AMED, PsycINFO and PEDro). Our primary outcomes will be pain intensity, patient-reported quality of life (QoL), and acceptability of treatment will be our secondary outcome. Risk of bias of the included trials will be assessed using the Cochrane risk of bias tool (RoB2). For each pairwise comparison between the different interventions, we will present mean differences (MDs) for pain intensity and QoL outcomes and Relative Risks (RRs) for acceptability, both with respective 95% confidence intervals (CIs). Initially, standard pairwise meta-analyses will be performed using a DerSimonian-Laird random effects model for all comparisons with at least two trials and then we will perform a frequentist NMA using the methodology of multivariate meta-analysis assuming a common heterogeneity parameter, using the mvmeta command and network suite in STATA. In the NMA, two different types of control group, such as placebo/sham and no intervention/waiting list will be combined as one node called “Control”. The competing interventions will be ranked using the P-score, which is the frequentist analogue of surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at immediate- (intervention duration of up to 2 weeks), short- (over 2 weeks up to 12 weeks) and long-terms (over 12 weeks). The confidence in the results from NMA will be assessed using the Confidence in Network Meta‐analysis (CINeMA) framework. Ethics and dissemination This work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal. Registration OSF (DOI: 10.17605/OSF.IO/7MS25) and registered in the PROSPERO database (CRD42020216374).

Background Refugees, and other forcibly displaced people, face mental distress and may be disproportionately affected by risk factors for suicide. Little is known about suicidal behaviour in these highly mobile populations because collecting timely, relevant, and reliable data is challenging. Methods and findings A systematic review was performed to identify studies of any design reporting on suicide, suicide attempts, or suicidal ideation among populations of displaced people. A sensitive electronic database search was performed in August 2020, and all retrieved studies were screened for relevance by two authors. Studies were categorised by the population being evaluated: refugees granted asylum, refugees living in temporary camps, asylum seekers, or internally displaced people. We distinguished between whether the sampling procedure in the studies was likely to be representative, or the sample examined a specific non-representative subgroup of displaced people (such as those already diagnosed with mental illness). Data on the rates of suicide or the prevalence of suicide attempts or suicidal ideation were extracted by one reviewer and verified by a second reviewer from each study and converted to common metrics. After screening 4347 articles, 87 reports of 77 unique studies were included. Of these, 53 were studies in representative samples, and 24 were based on samples of specific target populations. Most studies were conducted in high-income countries, and the most studied population subgroup was refugees granted asylum. There was substantial heterogeneity across data sources and measurement instruments utilised. Sample sizes of displaced people ranged from 33 to 196,941 in studies using general samples. Suicide rates varied considerably, from 4 to 290 per 100,000 person-years across studies. Only 8 studies were identified that compared suicide rates with the host population. The prevalence of suicide attempts ranged from 0.14% to 15.1% across all studies and varied according to the prevalence period evaluated. Suicidal ideation prevalence varied from 0.17% to 70.6% across studies. Among refugees granted asylum, there was evidence of a lower risk of suicide compared with the host population in 4 of 5 studies. In contrast, in asylum seekers there was evidence of a higher suicide risk in 2 of 3 studies, and of a higher risk of suicidal ideation among refugees living in camps in 2 of 3 studies compared to host populations. Conclusion While multiple studies overall have been published in the literature on this topic, the evidence base is still sparse for refugees in camps, asylum seekers, and internally displaced people. Less than half of the included studies reported on suicide or suicide attempt outcomes, with most reporting on suicidal ideation. International research networks could usefully define criteria, definitions, and study designs to help standardise and facilitate more research in this important area. Registration PROSPERO CRD42019137242.

BACKGROUND: Community-based primary-level workers (PWs) are an important strategy for addressing gaps in mental health service delivery in low- and middle-income countries. OBJECTIVES: To evaluate the effectiveness of PW-led treatments for persons with mental health symptoms in LMICs, compared to usual care. SEARCH METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, ICTRP, reference lists (to 20 June 2019). SELECTION CRITERIA: Randomised trials of PW-led or collaborative-care interventions treating people with mental health symptoms or their carers in LMICs. PWs included: primary health professionals (PHPs), lay health workers (LHWs), community non-health professionals (CPs). DATA COLLECTION AND ANALYSIS: Seven conditions were identified apriori and analysed by disorder and PW examining recovery, prevalence, symptom change, quality-of-life (QOL), functioning, service use (SU), and adverse events (AEs). Risk ratios (RRs) were used for dichotomous outcomes; mean difference (MDs), standardised mean differences (SMDs), or mean change differences (MCDs) for continuous outcomes. For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥0.80 large clinical effects. Analysis timepoints: T1 (6 months) post-intervention. MAIN RESULTS: Description of studies 95 trials (72 new since 2013) from 30 LMICs (25 trials from 13 LICs). Risk of bias Most common: detection bias, attrition bias (efficacy), insufficient protection against contamination. Intervention effects *Unless indicated, comparisons were usual care at T2. "Probably", "may", or "uncertain" indicates "moderate", "low," or "very low" certainty evidence. Adults with common mental disorders (CMDs) LHW-led interventions a. may increase recovery (2 trials, 308 participants; RR 1.29, 95%CI 1.06 to 1.56); b. may reduce prevalence (2 trials, 479 participants; RR 0.42, 95%CI 0.18 to 0.96); c. may reduce symptoms (4 trials, 798 participants; SMD -0.59, 95%CI -1.01 to -0.16); d. may improve QOL (1 trial, 521 participants; SMD 0.51, 95%CI 0.34 to 0.69); e. may slightly reduce functional impairment (3 trials, 1399 participants; SMD -0.47, 95%CI -0.8 to -0.15); f. may reduce AEs (risk of suicide ideation/attempts); g. may have uncertain effects on SU. Collaborative-care a. may increase recovery (5 trials, 804 participants; RR 2.26, 95%CI 1.50 to 3.43); b. may reduce prevalence although the actual effect range indicates it may have little-or-no effect (2 trials, 2820 participants; RR 0.57, 95%CI 0.32 to 1.01); c. may slightly reduce symptoms (6 trials, 4419 participants; SMD -0.35, 95%CI -0.63 to -0.08); d. may slightly improve QOL (6 trials, 2199 participants; SMD 0.34, 95%CI 0.16 to 0.53); e. probably has little-to-no effect on functional impairment (5 trials, 4216 participants; SMD -0.13, 95%CI -0.28 to 0.03); f. may reduce SU (referral to MH specialists); g. may have uncertain effects on AEs (death). Women with perinatal depression (PND) LHW-led interventions a. may increase recovery (4 trials, 1243 participants; RR 1.29, 95%CI 1.08 to 1.54); b. probably slightly reduce symptoms (5 trials, 1989 participants; SMD -0.26, 95%CI -0.37 to -0.14); c. may slightly reduce functional impairment (4 trials, 1856 participants; SMD -0.23, 95%CI -0.41 to -0.04); d. may have little-to-no effect on AEs (death); e. may have uncertain effects on SU. Collaborative-care a. has uncertain effects on symptoms/QOL/SU/AEs. Adults with post-traumatic stress (PTS) or CMDs in humanitarian settings LHW-led interventions a. may slightly reduce depression symptoms (5 trials, 1986 participants; SMD -0.36, 95%CI -0.56 to -0.15); b. probably slightly improve QOL (4 trials, 1918 participants; SMD -0.27, 95%CI -0.39 to -0.15); c. may have uncertain effects on symptoms (PTS)/functioning/SU/AEs. PHP-led interventions a. may reduce PTS symptom prevalence (1 trial, 313 participants; RR 5.50, 95%CI 2.50 to 12.10) and depression prevalence (1 trial, 313 participants; RR 4.60, 95%CI 2.10 to 10.08); b. may have uncertain effects on symptoms/functioning/SU/AEs. Adults with harmful/hazardous alcohol or substance use LHW-led interventions a. may increase recovery from harmful/hazardous alcohol use although the actual effect range indicates it may have little-or-no effect (4 trials, 872 participants; RR 1.28, 95%CI 0.94 to 1.74); b. may have little-to-no effect on the prevalence of methamphetamine use (1 trial, 882 participants; RR 1.01, 95%CI 0.91 to 1.13) and functional impairment (2 trials, 498 participants; SMD -0.14, 95%CI -0.32 to 0.03); c. probably slightly reduce risk of harmful/hazardous alcohol use (3 trials, 667 participants; SMD -0.22, 95%CI -0.32 to -0.11); d. may have uncertain effects on SU/AEs. PHP/CP-led interventions a. probably have little-to-no effect on recovery from harmful/hazardous alcohol use (3 trials, 1075 participants; RR 0.93, 95%CI 0.77 to 1.12) or QOL (1 trial, 560 participants; MD 0.00, 95%CI -0.10 to 0.10); b. probably slightly reduce risk of harmful/hazardous alcohol and substance use (2 trials, 705 participants; SMD -0.20, 95%CI -0.35 to -0.05; moderate-certainty evidence); c. may have uncertain effects on prevalence (cannabis use)/SU/AEs. PW-led interventions for alcohol/substance dependence a. may have uncertain effects. Adults with severe mental disorders *Comparisons were specialist-led care at T1. LHW-led interventions a. may have little-to-no effect on caregiver burden (1 trial, 253 participants; MD -0.04, 95%CI -0.18 to 0.11); b. may have uncertain effects on symptoms/functioning/SU/AEs. PHP-led or collaborative-care a. may reduce functional impairment (7 trials, 874 participants; SMD -1.13, 95%CI -1.78 to -0.47); b. may have uncertain effects on recovery/relapse/symptoms/QOL/SU. Adults with dementia and carers PHP/LHW-led carer interventions a. may have little-to-no effect on the severity of behavioural symptoms in dementia patients (2 trials, 134 participants; SMD -0.26, 95%CI -0.60 to 0.08); b. may reduce carers' mental distress (2 trials, 134 participants; SMD -0.47, 95%CI -0.82 to -0.13); c. may have uncertain effects on QOL/functioning/SU/AEs. Children with PTS or CMDs LHW-led interventions a. may have little-to-no effect on PTS symptoms (3 trials, 1090 participants; MCD -1.34, 95%CI -2.83 to 0.14); b. probably have little-to-no effect on depression symptoms (3 trials, 1092 participants; MCD -0.61, 95%CI -1.23 to 0.02) or on functional impairment (3 trials, 1092 participants; MCD -0.81, 95%CI -1.48 to -0.13); c. may have little-or-no effect on AEs. CP-led interventions a. may have little-to-no effect on depression symptoms (2 trials, 602 participants; SMD -0.19, 95%CI -0.57 to 0.19) or on AEs; b. may have uncertain effects on recovery/symptoms(PTS)/functioning.AUTHORS' CONCLUSIONS: PW-led interventions show promising benefits in improving outcomes for CMDs, PND, PTS, harmful alcohol/substance use, and dementia carers in LMICs.

Background Vaccines may reduce antibiotic use and the development of resistance. Objectives To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. Data sources Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. Study eligibility criteria Randomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018. Participants Any population. Interventions Vaccines versus placebo, no vaccine or another vaccine. Methods Titles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. Results In all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0–38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54–0·70) and probably reduce community antibiotic use in children aged 3–15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58–0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87–0·99) and reduces illness episodes requiring antibiotics in children aged 12–35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75–0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. Conclusions The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO registration CRD42018103881.

ObjectiveTo determine the effectiveness of conservative treatment (CT) on pain and function in patients with patellar tendinopathy (PT) compared with minimal intervention (MI) or other invasive intervention, or in addition to decline eccentric squat.MethodsSearches were performed in MEDLINE, Embase, Cochrane, PEDro, SPORTDiscus, CINAHL and AMED databases. All randomised trials that evaluated CT (any intervention not involving invasive procedures or medication) in individuals with PT were included. Two reviewers screened studies, extracted data and assessed risk of bias of all included studies. Where suitable, meta-analyses were conducted; we assessed certainty of the evidence using GRADE methodology.ResultsWhen compared with MI, CT did not improve pain (weighted mean difference (WMD) −2.6, 95% CI −6.5 to 1.2) or function (WMD 1.8, 95% CI −2.4 to 6.1) in the short-term (up to 3 months) follow-up. When compared with invasive intervention, CT did not improve pain (WMD 0.7, 95% CI −0.1 to 1.4) or function (WMD −6.6, 95% CI −13.3 to 0.2) in the short-term follow-up. No overall effects were found for combined CT (when a conservative intervention was added to decline eccentric squat) on pain (WMD −0.5, 95% CI −1.4 to 0.4) or function (WMD −2.3, 95 % –9.1 to 4.6) at short-term follow-up. Single studies showed an effect on pain with iontophoresis at short-term follow-up (d = 2.42) or dry needling at medium/long-term follow-up (d = 1.17) and function with exercise intervention at medium/long-term follow-up (over 3 months) (d = 0.83).Summary/ConclusionOur estimates of treatment effect have only low to very low certainty evidence to support them. This field of sports medicine/sports physiotherapy urgently needs larger, high-quality studies with pain and function among the potential primary outcomes.

Background Ministries of health, donors, and other decision‐makers are exploring how they can use mobile technologies to acquire accurate and timely statistics on births and deaths. These stakeholders have called for evidence‐based guidance on this topic. This review was carried out to support World Health Organization (WHO) recommendations on digital interventions for health system strengthening. Objectives Primary objective: To assess the effects of birth notification and death notification via a mobile device, compared to standard practice. Secondary objectives: To describe the range of strategies used to implement birth and death notification via mobile devices and identify factors influencing the implementation of birth and death notification via mobile devices. Search methods We searched CENTRAL, MEDLINE, Embase, the Global Health Library, and POPLINE (August 2, 2019). We searched two trial registries (August 2, 2019). We also searched Epistemonikos for related systematic reviews and potentially eligible primary studies (August 27, 2019). We conducted a grey literature search using mHealthevidence.org (August 15, 2017) and issued a call for papers through popular digital health communities of practice. Finally, we conducted citation searches of included studies in Web of Science and Google Scholar (May 15, 2020). We searched for studies published after 2000 in any language. Selection criteria For the primary objective, we included individual and cluster‐randomised trials; cross‐over and stepped‐wedge study designs; controlled before‐after studies, provided they have at least two intervention sites and two control sites; and interrupted time series studies. For the secondary objectives, we included any study design, either quantitative, qualitative, or descriptive, that aimed to describe current strategies for birth and death notification via mobile devices; or to explore factors that influence the implementation of these strategies, including studies of acceptability or feasibility. For the primary objective, we included studies that compared birth and death notification via mobile devices with standard practice. For the secondary objectives, we included studies of birth and death notification via mobile device as long as we could extract data relevant to our secondary objectives. We included studies of all cadres of healthcare providers, including lay health workers; administrative, managerial, and supervisory staff; focal individuals at the village or community level; children whose births were being notified and their parents/caregivers; and individuals whose deaths were being notified and their relatives/caregivers. Data collection and analysis For the primary objective, two authors independently screened all records, extracted data from the included studies and assessed risk of bias. For the analyses of the primary objective, we reported means and proportions, where appropriate. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and we prepared a 'Summary of Findings' table. For the secondary objectives, two authors screened all records, one author extracted data from the included studies and assessed methodological limitations using the WEIRD tool and a second author checked the data and assessments. We carried out a framework analysis using the Supporting the Use of Research Evidence (SURE) framework to identify themes in the data. We used the GRADE‐CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in the evidence and we prepared a 'Summary of Qualitative Findings' table. Main results For the primary objective, we included one study, which used a controlled before‐after study design. The study was conducted in Lao People’s Democratic Republic and assessed the effect of using mobile devices for birth notification on outcomes related to coverage and timeliness of Hepatitis B vaccination. However, we are uncertain of the effect of this approach on these outcomes because the certainty of this evidence was assessed as very low. The included study did not assess resource use or unintended consequences. For the primary objective, we did not identify any studies using mobile devices for death notification. For the secondary objective, we included 21 studies. All studies were conducted in low‐ or middle‐income settings. They focussed on identification of births and deaths in rural, remote, or marginalised populations who are typically under‐represented in civil registration processes or traditionally seen as having poor access to health services. The review identified several factors that could influence the implementation of birth‐death notification via mobile device. These factors were tied to the health system, the person responsible for notifying, the community and families; and include: ‐ Geographic barriers that could prevent people’s access to birth‐death notification and post‐notification services ‐ Access to health workers and other notifiers with enough training, supervision, support, and incentives ‐ Monitoring systems that ensure the quality and timeliness of the birth and death data ‐ Legal frameworks that allow births and deaths to be notified by mobile device and by different types of notifiers ‐ Community awareness of the need to register births and deaths ‐ Socio‐cultural norms around birth and death ‐ Government commitment ‐ Cost to the system, to health workers and to families ‐ Access to electricity and network connectivity, and compatibility with existing systems ‐ Systems that protect data confidentiality We have low to moderate confidence in these findings. This was mainly because of concerns about methodological limitations and data adequacy. Authors' conclusions We need more, well‐designed studies of the effect of birth and death notification via mobile devices and on factors that may influence its implementation., Plain language summary Birth and death notification via mobile devices: a mixed methods review What is the aim of this review? In this Cochrane Review, we aimed to assess the effect of using mobile devices to notify births and deaths. We also aimed to describe how these mobile solutions are being used in practice and the factors that influence their use. We collected and analysed all relevant studies to answer these questions. Key messages We know very little about the effects of using mobile devices to notify births and deaths. Factors that can influence the implementation of this approach include factors tied to the health system and the notification system, the person responsible for notifying, the community, and the families involved. What was studied in the review? By registering notified births and deaths, governments can track the health of their population, identify needs and problems, and design better services. In many countries, births and deaths are not properly registered. Sometimes this is because government systems are poorly designed to facilitate registration, government workers do not have proper training, people live far from government services, or are not aware of the need to register births or deaths. In many cases, registration is affected by delays in or lack of birth or death notification. Governments are starting to use mobile devices such as mobile phones to reduce problems with birth or death notification. In some settings, members of the public, healthcare workers and others use mobile phones to notify a birth or death to the health system or to a central registration system. The main aim of our review was to assess what happens when people use mobile devices to notify births and deaths, compared to other systems or no systems at all. For instance, do they register more birth and deaths, and do they do this at the right time? And does this lead more babies and children to use or receive health services, such as immunisation? We also wanted to find out how people are using these mobile systems in practice and what influences their use. What are the main results of the review? We found 21 relevant studies. All of the studies were from low‐ or middle‐income countries. Most of these studies focussed on the notification of births and deaths in rural, remote, or marginalised populations who are often under‐represented in birth or death registration processes or have poor access to health services. Only one of the studies assessed the effect of using mobile devices for notification systems. This study focussed on birth notification. We did not find any studies that assessed the effect of using mobile devices for death notification. We are uncertain of the effect of this approach on the number of births and deaths that are properly notified because the certainty of this evidence was assessed as very low. The other studies had information about how people use the mobile device‐based birth and death notification systems in practice. These studies pointed to several factors that could influence the implementation of birth‐death notification via mobile devices. These factors were tied to the health system and the notification system, the person responsible for notifying, the community, and the families involved. They include: ‐ Geographic barriers that could prevent people’s access to birth‐death notification and post‐notification services ‐ Access to health workers and other notifiers with enough training, supervision, support, and incentives ‐ Monitoring systems that ensure the quality and timeliness of the birth and death data ‐ Legal frameworks that allow births and deaths to be notified by mobile device and by different types of notifiers ‐ Community awareness of the need to register births and deaths ‐ Socio‐cultural norms around birth and death ‐ Government commitment ‐ Cost to the system, to health workers and to families ‐ Access to electricity and network connectivity, and compatibility with existing systems ‐ Systems that protect data confidentiality We have low to moderate confidence in these findings. This was mainly because of the ways in which the studies were designed and small amounts of data. How up‐to‐date is this review? We searched for studies that had been published up to August 2, 2019.

Background: Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance. Objectives: To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly. Search methods: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021. Selection criteria: We included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. Data collection and analysis: We followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events. Main results: We identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo. a. Effectiveness of tocilizumab for patients with COVID-19. Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I2 = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I2 = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I2 = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I2 = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19. The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I2 = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I2 = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo. The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded. No data were available for other critical outcomes. Authors' conclusions: On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com).

ObjectiveWe undertook a systematic review of the literature to explore the prevalence of post-traumatic stress disorder (PTSD) in Palestinian children and adolescents exposed to political violence. This is the first systematic review and meta-analysis of the prevalence of PTSD in this population.MethodsPubMed, Embase, PsycInfo, Google Scholar and Cochrane library were searched until June 2020. To estimate the prevalence of PTSD, sub-group and meta-analysis were conducted.ResultsThe search resulted in 2786 studies, of which 28 articles representing 32 samples with a total of 15,121 participants from Gaza Strip and West Bank met either the DSM-4 or DSM-5 criteria and were included. The pooled prevalence of PTSD was 36% (95% CI 30–41%;I298.6%) and ranged from 6% to 70%. Sub-group analysis showed that the PTSD prevalence did not differ according to region (West Bank, Gaza Strip) and tended to decrease after including only studies using a representative sample (ppConclusionWe identified high prevalence of PTSD among Palestinian children and adolescents exposed to political violence. However, the pooled results should be interpreted with caution, due to the high heterogeneity and risk of bias in the included studies. These limitations also reflect the challenge in conceptualizing and measuring PTSD in the Palestinian context with a background of continuous and cumulative trauma. Understanding the contextual factors and developing locally adapted survey measures are of relevance to future research, public health planning, and the provision of mental healthcare in Palestine.

Background Health systems need timely and reliable access to essential medicines and health commodities, but problems with access are common in many settings. Mobile technologies offer potential low‐cost solutions to the challenge of drug distribution and commodity availability in primary healthcare settings. However, the evidence on the use of mobile devices to address commodity shortages is sparse, and offers no clear way forward. Objectives Primary objective To assess the effects of strategies for notifying stock levels and digital tracking of healthcare‐related commodities and inventory via mobile devices across the primary healthcare system Secondary objectives To describe what mobile device strategies are currently being used to improve reporting and digital tracking of health commodities To identify factors influencing the implementation of mobile device interventions targeted at reducing stockouts of health commodities Search methods We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Global Index Medicus WHO, POPLINE K4Health, and two trials registries in August 2019. We also searched Epistemonikos for related systematic reviews and potentially eligible primary studies. We conducted a grey literature search using mHealthevidence.org, and issued a call for papers through popular digital health communities of practice. Finally, we conducted citation searches of included studies. We searched for studies published after 2000, in any language. Selection criteria For the primary objective, we included individual and cluster‐randomised trials, controlled before‐after studies, and interrupted time series studies. For the secondary objectives, we included any study design, which could be quantitative, qualitative, or descriptive, that aimed to describe current strategies for commodity tracking or stock notification via mobile devices; or aimed to explore factors that influenced the implementation of these strategies, including studies of acceptability or feasibility. We included studies of all cadres of healthcare providers, including lay health workers, and others involved in the distribution of health commodities (administrative staff, managerial and supervisory staff, dispensary staff); and all other individuals involved in stock notification, who may be based in a facility or a community setting, and involved with the delivery of primary healthcare services. We included interventions aimed at improving the availability of health commodities using mobile devices in primary healthcare settings. For the primary objective, we included studies that compared health commodity tracking or stock notification via mobile devices with standard practice. For the secondary objectives, we included studies of health commodity tracking and stock notification via mobile device, if we could extract data relevant to our secondary objectives. Data collection and analysis For the primary objective, two authors independently screened all records, extracted data from the included studies, and assessed the risk of bias. For the analyses of the primary objectives, we reported means and proportions where appropriate. We used the GRADE approach to assess the certainty of the evidence, and prepared a 'Summary of findings' table. For the secondary objective, two authors independently screened all records, extracted data from the included studies, and applied a thematic synthesis approach to synthesise the data. We assessed methodological limitation using the Ways of Evaluating Important and Relevant Data (WEIRD) tool. We used the GRADE‐CERQual approach to assess our confidence in the evidence, and prepared a 'Summary of qualitative findings' table. Main results Primary objective For the primary objective, we included one controlled before‐after study conducted in Malawi. We are uncertain of the effect of cStock plus enhanced management, or cStock plus effective product transport on the availability of commodities, quality and timeliness of stock management, and satisfaction and acceptability, because we assessed the evidence as very low‐certainty. The study did not report on resource use or unintended consequences. Secondary objective For the secondary objectives, we included 16 studies, using a range of study designs, which described a total of eleven interventions. All studies were conducted in African (Tanzania, Kenya, Malawi, Ghana, Ethiopia, Cameroon, Zambia, Liberia, Uganda, South Africa, and Rwanda) and Asian (Pakistan and India) countries. Most of the interventions aimed to make data about stock levels and potential stockouts visible to managers, who could then take corrective action to address them. We identified several factors that may influence the implementation of stock notification and tracking via mobile device. These include challenges tied to infrastructural issues, such as poor access to electricity or internet, and broader health systems issues, such as drug shortages at the national level which cannot be mitigated by interventions at the primary healthcare level (low confidence). Several factors were identified as important, including strong partnerships with local authorities, telecommunication companies, technical system providers, and non‐governmental organizations (very low confidence); availability of stock‐level data at all levels of the health system (low confidence); the role of supportive supervision and responsive management (moderate confidence); familiarity and training of health workers in the use of the digital devices (moderate confidence); availability of technical programming expertise for the initial development and ongoing maintenance of the digital systems (low confidence); incentives, such as phone credit for personal use, to support regular use of the system (low confidence); easy‐to‐use systems built with user participation (moderate confidence); use of basic or personal mobile phones to support easier adoption (low confidence); consideration for software features, such as two‐way communication (low confidence); and data availability in an easy‐to‐use format, such as an interactive dashboard (moderate confidence). Authors' conclusions We need more, well‐designed, controlled studies comparing stock notification and commodity management via mobile devices with paper‐based commodity management systems. Further studies are needed to understand the factors that may influence the implementation of such interventions, and how implementation considerations differ by variations in the intervention., Plain language summary Using mobile phones to keep track of medicines and notify superiors when more are needed What is the aim of this review? In this Cochrane Review, we aimed to assess if health workers would have better access to medicines and other supplies, if they used mobile phones or other mobile devices to keep track of the amount of supplies they had available, and to notify superiors when they needed more supplies. We also described how health workers are currently using these mobile systems, and what factors influence their use. Key messages We do not know if using mobile phones to keep track of medical supplies gives primary healthcare workers better access to these supplies. This is because the certainty of the available evidence was very low. However, the evidence does point to several factors that could influence the implementation of these systems. These include the sharing of data across all levels of the health system; reliable access to electricity and the internet; easy‐to‐use and functional phones and systems; good technical support; and sufficient training and supervision. Well‐functioning digital systems will only succeed if medical supplies are actually available. What was studied in the review? Healthcare workers need medicines, vaccines, syringes, and other supplies to do their jobs properly. But many healthcare settings, particularly in poor countries, often lack supplies because governments cannot afford to buy them, or because they do not have good systems for distributing them to the right places at the right time. To address some of these problems, managers and health workers can use mobile phones to keep track of supplies, decide how much more to order and when, and let people at higher levels of the system know when supplies are running low. The main aim of our review was to find out if health workers who use these mobile systems had better access to supplies than health workers using other systems, or no systems at all. We also looked at how these mobile systems are being used in primary healthcare settings, and the factors that influences their use. What are the main results of the review? We found one study from Malawi that measured the effect of mobile phone systems on access to medicines and supplies in health facilities. However, we do not know whether these systems improve access or not, because the certainty of this evidence was very low. We found 16 studies conducted in African and Asian countries, in which study authors identified several factors that could help to set up systems successfully. ‐ Study authors suggested that allowing healthcare officials at all levels of the healthcare system to see the data could help them to respond on time and avoid supply shortages (low confidence). ‐ Study authors highlighted how poor access to electricity and internet could make it difficult for health workers to charge phones and send data (moderate confidence). ‐ Study authors pointed to the importance of user‐friendly systems, built with user participation (moderate confidence); access to technical experts to develop and maintain the system (low confidence); proper support and supervision for health workers (moderate confidence); and training of health workers in how to use the mobile system itself (moderate confidence). ‐ One author suggested that adding phone credits to health workers’ mobile phones for their personal use, could motivate them, and improve their use of the system (low confidence). Study authors also suggested several mobile phone functions that could be helpful to health workers using these systems. These included phones that could take pictures and map geographic locations, systems that allowed toll‐free text messaging, two‐way communication, and easy sharing of information (low confidence). But study authors also suggested that health workers might find it easier to use basic phones and maintain their own personal phones (low confidence). ‐ Study authors emphasised that digital notification systems will only give health workers better access to supplies if the supplies are actually available at the district or national level (low confidence). How up‐to‐date is this review? We searched for studies that had been published up to August 2019.

Importance Fibromyalgia is a chronic condition that results in a significant burden to individuals and society. Objective To investigate the effectiveness of therapies for reducing pain and improving quality of life (QOL) in people with fibromyalgia. Data Sources Searches were performed in the MEDLINE, Cochrane, Embase, AMED, PsycInfo, and PEDro databases without language or date restrictions on December 11, 2018, and updated on July 15, 2020. Study Selection All published randomized or quasi-randomized clinical trials that investigated therapies for individuals with fibromyalgia were screened for inclusion. Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias using the 0 to 10 PEDro scale. Effect sizes for specific therapies were pooled using random-effects models. The quality of evidence was assessed using the Grading of Recommendations Assessment (GRADE) approach. Main Outcomes and Measures Pain intensity measured by the visual analog scale, numerical rating scales, and other valid instruments and QOL measured by the Fibromyalgia Impact Questionnaire. Results A total of 224 trials including 29 962 participants were included. High-quality evidence was found in favor of cognitive behavioral therapy (weighted mean difference [WMD], −0.9; 95% CI, −1.4 to −0.3) for pain in the short term and was found in favor of central nervous system depressants (WMD, −1.2 [95% CI, −1.6 to −0.8]) and antidepressants (WMD, −0.5 [95% CI, −0.7 to −0.4]) for pain in the medium term. There was also high-quality evidence in favor of antidepressants (WMD, −6.8 [95% CI, −8.5 to −5.2]) for QOL in the short term and in favor of central nervous system depressants (WMD, −8.7 [95% CI, −11.3 to −6.0]) and antidepressants (WMD, −3.5 [95% CI, −4.5 to −2.5]) in the medium term. However, these associations were small and did not exceed the minimum clinically important change (2 points on an 11-point scale for pain and 14 points on a 101-point scale for QOL). Evidence for long-term outcomes of interventions was lacking. Conclusions and Relevance This systematic review and meta-analysis suggests that most of the currently available therapies for the management of fibromyalgia are not supported by high-quality evidence. Some therapies may reduce pain and improve QOL in the short to medium term, although the effect size of the associations might not be clinically important to patients.

International audience; These authors propose an “evidence ecosystem” for COVID-19–related studies that minimizes multiple low-quality reviews and helps connect evidence generation, synthesis, and decision making.

Background Quality of low back pain (LBP) information offered on YouTube ™ is unclear. Objective To describe the current low back pain information available on YouTube ™ and determine if these videos report information that aligns with clinical guidelines. Further analysis explored whether specific features of the videos explain their popularity. Methods A cross-sectional observational study was conducted on videos related to LBP on YouTube™ with the 200 most viewed videos using the term “low back pain.” The videos were independently viewed and assessed by two researchers for specific video characteristics, LBP specific content, and compliance with guidelines. The association between video characteristics or content with popularity (i.e., views, likes, dislikes, and comments) was investigated using regression models. Results The median number of views was 2 018 167. Only 59 (29.5%) of the videos reported at least one diagnostic recommendation from clinical guidelines, and only 100 (50%) reported a treatment recommendation that aligned with clinical guidelines. Apart from year of upload, no variables were identified that were independently associated with popularity or engagement of the videos. Conclusion The information related to LBP offered on YouTube™ is often not evidence-based and there is the tendency to prioritize information on interventions rather than understanding the LBP process. Factors related to engagement with content about LBP on YouTube™ remains uncertain, indicating further need for knowledge translation in this field.

Background The burden of poor sexual and reproductive health (SRH) worldwide is substantial, disproportionately affecting those living in low‐ and middle‐income countries. Targeted client communication (TCC) delivered via mobile devices (MD) (TCCMD) may improve the health behaviours and service use important for sexual and reproductive health. Objectives To assess the effects of TCC via MD on adolescents' knowledge, and on adolescents’ and adults' sexual and reproductive health behaviour, health service use, and health and well‐being. Search methods In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. Selection criteria We included randomised controlled trials of TCC via MD to improve sexual and reproductive health behaviour, health service use, and health and well‐being. Eligible comparators were standard care or no intervention, non‐digital TCC, and digital non‐targeted communication. Data collection and analysis We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross‐checked by a second. We have presented results separately for adult and adolescent populations, and for each comparison. Main results We included 40 trials (27 among adult populations and 13 among adolescent populations) with a total of 26,854 participants. All but one of the trials among adolescent populations were conducted in high‐income countries. Trials among adult populations were conducted in a range of high‐ to low‐income countries. Among adolescents, nine interventions were delivered solely through text messages; four interventions tested text messages in combination with another communication channel, such as emails, multimedia messaging, or voice calls; and one intervention used voice calls alone. Among adults, 20 interventions were delivered through text messages; two through a combination of text messages and voice calls; and the rest were delivered through other channels such as voice calls, multimedia messaging, interactive voice response, and instant messaging services. Adolescent populations TCCMD versus standard care TCCMD may increase sexual health knowledge (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.23 to 1.71; low‐certainty evidence). TCCMD may modestly increase contraception use (RR 1.19, 95% CI 1.05 to 1.35; low‐certainty evidence). The effects on condom use, antiretroviral therapy (ART) adherence, and health service use are uncertain due to very low‐certainty evidence. The effects on abortion and STI rates are unknown due to lack of studies. TCCMD versus non‐digital TCC (e.g. pamphlets) The effects of TCCMD on behaviour (contraception use, condom use, ART adherence), service use, health and wellbeing (abortion and STI rates) are unknown due to lack of studies for this comparison. TCCMD versus digital non‐targeted communication The effects on sexual health knowledge, condom and contraceptive use are uncertain due to very low‐certainty evidence. Interventions may increase health service use (attendance for STI/HIV testing, RR 1.61, 95% CI 1.08 to 2.40; low‐certainty evidence). The intervention may be beneficial for reducing STI rates (RR 0.61, 95% CI 0.28 to 1.33; low‐certainty evidence), but the confidence interval encompasses both benefit and harm. The effects on abortion rates and on ART adherence are unknown due to lack of studies. We are uncertain whether TCCMD results in unintended consequences due to lack of evidence. Adult populations TCCMD versus standard care For health behaviours, TCCMD may modestly increase contraception use at 12 months (RR 1.17, 95% CI 0.92 to 1.48) and may reduce repeat abortion (RR 0.68 95% CI 0.28 to 1.66), though the confidence interval encompasses benefit and harm (low‐certainty evidence). The effect on condom use is uncertain. No study measured the impact of this intervention on STI rates. TCCMD may modestly increase ART adherence (RR 1.13, 95% CI 0.97 to 1.32, low‐certainty evidence, and standardised mean difference 0.44, 95% CI ‐0.14 to 1.02, low‐certainty evidence). TCCMD may modestly increase health service utilisation (RR 1.17, 95% CI 1.04 to 1.31; low‐certainty evidence), but there was substantial heterogeneity (I2 = 85%), with mixed results according to type of service utilisation (i.e. attendance for STI testing; HIV treatment; voluntary male medical circumcision (VMMC); VMMC post‐operative visit; post‐abortion care). For health and well‐being outcomes, there may be little or no effect on CD4 count (mean difference 13.99, 95% CI ‐8.65 to 36.63; low‐certainty evidence) and a slight reduction in virological failure (RR 0.86, 95% CI 0.73 to 1.01; low‐certainty evidence). TCCMD versus non‐digital TCC No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may modestly increase in service attendance overall (RR: 1.12, 95% CI 0.92‐1.35, low certainty evidence), however the confidence interval encompasses benefit and harm. TCCMD versus digital non‐targeted communication No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may increase service utilisation overall (RR: 1.71, 95% CI 0.67‐4.38, low certainty evidence), however the confidence interval encompasses benefit and harm and there was considerable heterogeneity (I2 = 72%), with mixed results according to type of service utilisation (STI/HIV testing, and VMMC). Few studies reported on unintended consequences. One study reported that a participant withdrew from the intervention as they felt it compromised their undisclosed HIV status. Authors' conclusions TCCMD may improve some outcomes but the evidence is of low certainty. The effect on most outcomes is uncertain/unknown due to very low certainty evidence or lack of evidence. High quality, adequately powered trials and cost effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCC delivered by mobile devices. Given the sensitivity and stigma associated with sexual and reproductive health future studies should measure unintended consequences, such as partner violence or breaches of confidentiality., Plain language summary Communicating to young people and adults through their mobile devices to improve sexual and reproductive health Aim of this review We assessed the effect of sending targeted messages by mobile devices to young people and adults about their sexual and reproductive health (SRH). Sexually transmitted infections (STIs) and unintended pregnancies are important causes of illness and early death worldwide. Key messages There are gaps in the evidence regarding the effects of targeted messages by mobile devices to young people and adults about their SRH. These types of messages may have benefits in a few areas. However, the existing evidence is often of low or very low certainty. What was studied in the review? Targeted client communication (TCC) is an intervention in which the health system sends information to particular people, based on their health status or other factors specific to that population group. Common types of TCC are text messages that remind people to go to appointments or that offer healthcare information and support. Our review assessed whether TCC can change people’s behaviour, use of health services, and health and well‐being. We focused on communication about SRH to young people (aged 10 to 24 years), and to adults. What happens when young people receive targeted messages by mobile device? Compared to people who get no messages Young people may have better SRH knowledge and may use contraceptives slightly more. We don't know if the messages affect young people's condom use; use of SRH services; or the number testing positive for STIs, needing abortions, or adhering to HIV medication, because the evidence is missing or of very low certainty. Compared to people who get messages sent in other ways We do not know what the effect of the messages is because the evidence is missing. Compared to people who get untargeted messages We don't know whether the messages improve SRH knowledge or increase condom or contraceptive use because the certainty of the evidence is very low. The messages may reduce the number of people who get STIs (but it is possible they increase, or make little or no difference to, STIs). The messages may increase the number of young people who attend services for testing for STIs/HIV. We don't know whether the messages affect the number of young people having abortions or help them to take their HIV medication because the evidence is missing. We are uncertain if the messages lead to more unintended consequences among young people than no messages, or other types of communication. What happens when adults receive targeted messages by mobile device? Compared to people who get no messages The messages may slightly increase contraceptive use. They may also reduce the number of adults who need repeated abortions, although it is also possible they increase, or make little or no difference to, the number of abortions. We don't know whether the messages affect adults' condom use or the number of STIs because the evidence is of very low certainty, or missing. The messages may slightly increase adults' adherence to HIV medication among adults with HIV, but may make little or no difference to CD4 count and slightly improve viral load. The messages may slightly increase adults' use of SRH services overall, but results were mixed according to type of health service. Compared to people who get messages sent in other ways Adults receiving messages may attend SRH services more overall, but the evidence is mixed. We do not know what the effect of messages is on other behaviours and health because we lack evidence. Compared to people who get untargeted messages Adults receiving messages may attend SRH services more overall, but the evidence is mixed. We don't know what the effect of messages is on other behaviours and health because we lack evidence. We are uncertain if the messages lead to more unintended consequences among adults than no messages, or other types of communication. How up‐to‐date is this review? We searched for studies that had been published up to August 2017. We carried out a search update in July 2019 and relevant studies are reported in the 'Characteristics of studies awaiting classification' section.

ObjectivesMediation analysis is a widely used quantitative method for investigating how interventions and exposures in randomised controlled trials and observational studies have an effect on healthcare outcomes. This study aimed to assess the importance of items that should be considered in a consensus meeting aimed at developing a guideline for reporting mediation analyses.DesignInternational online Delphi study.ParticipantsInternational experts in the development and application of mediation analysis.Main outcome measuresThe Delphi panel were asked to rate the importance of a list of items for inclusion in a guideline for reporting mediation analyses. Thresholds for disagreement and consensus on importance for inclusion were specified a priori. We used the Research ANd Development/University of California Los Angeles appropriateness method to quantitatively assess the importance for inclusion and panel agreement.ResultsNineteen expert panellists (10 female) from seven countries agreed to participate. All panellists contributed to all three rounds conducted between 10 June 2019 and 6 November 2019. The panel reached consensus on 34 unique reporting items for study design, analytic procedures and effect estimates, with three items rated ‘optional’. Panellists added one extra item and provided 60 qualitative comments for item refinement and prioritisation.ConclusionThis Delphi study used a rigorous consensus process to reach consensus on 34 reporting items for studies that use mediation analysis. These results will inform a consensus meeting that will consolidate a core set of recommended items for reporting mediation analyses.

BACKGROUND: This is an update of a Cochrane Review published in 2014. Chronic non-specific low back pain (LBP) has become one of the main causes of disability in the adult population around the world. Although therapeutic ultrasound is not recommended in recent clinical guidelines, it is frequently used by physiotherapists in the treatment of chronic LBP. OBJECTIVES: The objective of this review was to determine the effectiveness of therapeutic ultrasound in the management of chronic non-specific LBP. A secondary objective was to determine the most effective dosage and intensity of therapeutic ultrasound for chronic LBP. SEARCH METHODS: We performed electronic searches in CENTRAL, MEDLINE, Embase, CINAHL, PEDro, Index to Chiropractic Literature, and two trials registers to 7 January 2020. We checked the reference lists of eligible studies and relevant systematic reviews and performed forward citation searching. SELECTION CRITERIA: We included randomised controlled trials (RCTs) on therapeutic ultrasound for chronic non-specific LBP. We compared ultrasound (either alone or in combination with another treatment) with placebo or other interventions for chronic LBP. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias of each trial and extracted the data. We performed a meta-analysis when sufficient clinical and statistical homogeneity existed. We determined the certainty of the evidence for each comparison using the GRADE approach. MAIN RESULTS: We included 10 RCTs involving a total of 1025 participants with chronic LBP. The included studies were carried out in secondary care settings in Turkey, Iran, Saudi Arabia, Croatia, the UK, and the USA, and most applied therapeutic ultrasound in addition to another treatment, for six to 18 treatment sessions. The risk of bias was unclear in most studies. Eight studies (80%) had unclear or high risk of selection bias; no studies blinded care providers to the intervention; and only five studies (50%) blinded participants. There was a risk of selective reporting in eight studies (80%), and no studies adequately assessed compliance with the intervention. There was very low-certainty evidence (downgraded for imprecision, inconsistency, and limitations in design) of little to no difference between therapeutic ultrasound and placebo for short-term pain improvement (mean difference (MD) -7.12, 95% confidence interval (CI) -17.99 to 3.75; n = 121, 3 RCTs; 0-to-100-point visual analogue scale (VAS)). There was also moderate-certainty evidence (downgraded for imprecision) of little to no difference in the number of participants achieving a 30% reduction in pain in the short term (risk ratio 1.08, 95% CI 0.81 to 1.44; n = 225, 1 RCT). There was low-certainty evidence (downgraded for imprecision and limitations in design) that therapeutic ultrasound has a small effect on back-specific function compared with placebo in the short term (standardised mean difference -0.29, 95% CI -0.51 to -0.07 (MD -1.07, 95% CI -1.89 to -0.26; Roland Morris Disability Questionnaire); n = 325; 4 RCTs), but this effect does not appear to be clinically important. There was moderate-certainty evidence (downgraded for imprecision) of little to no difference between therapeutic ultrasound and placebo on well-being (MD -2.71, 95% CI -9.85 to 4.44; n = 267, 2 RCTs; general health subscale of the 36-item Short Form Health Survey (SF-36)). Two studies (n = 486) reported on overall improvement and satisfaction between groups, and both reported little to no difference between groups (low-certainty evidence, downgraded for serious imprecision). One study (n = 225) reported on adverse events and did not identify any adverse events related to the intervention (low-certainty evidence, downgraded for serious imprecision). No study reported on disability for this comparison. We do not know whether therapeutic ultrasound in addition to exercise results in better outcomes than exercise alone because the certainty of the evidence for all outcomes was very low (downgraded for imprecision and serious limitations in design). The estimate effect for pain was in favour of the ultrasound plus exercise group (MD -21.1, 95% CI -27.6 to -14.5; n = 70, 2 RCTs; 0-to-100-point VAS) at short term. Regarding back-specific function (MD - 0.41, 95% CI -3.14 to 2.32; n = 79, 2 RCTs; Oswestry Disability Questionnaire) and well-being (MD -2.50, 95% CI -9.53 to 4.53; n = 79, 2 RCTs; general health subscale of the SF-36), there was little to no difference between groups at short term. No studies reported on the number of participants achieving a 30% reduction in pain, patient satisfaction, disability, or adverse events for this comparison. AUTHORS' CONCLUSIONS: The evidence from this systematic review is uncertain regarding the effect of therapeutic ultrasound on pain in individuals with chronic non-specific LBP. Whilst there is some evidence that therapeutic ultrasound may have a small effect on improving low back function in the short term compared to placebo, the certainty of evidence is very low. The true effect is likely to be substantially different. There are few high-quality randomised trials, and the available trials were very small. The current evidence does not support the use of therapeutic ultrasound in the management of chronic LBP.

Background The global burden of poor maternal, neonatal, and child health (MNCH) accounts for more than a quarter of healthy years of life lost worldwide. Targeted client communication (TCC) via mobile devices (MD) (TCCMD) may be a useful strategy to improve MNCH. Objectives To assess the effects of TCC via MD on health behaviour, service use, health, and well‐being for MNCH. Search methods In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. Selection criteria We included randomised controlled trials that assessed TCC via MD to improve MNCH behaviour, service use, health, and well‐being. Eligible comparators were usual care/no intervention, non‐digital TCC, and digital non‐targeted client communication. Data collection and analysis We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross‐checked by a second. Main results We included 27 trials (17,463 participants). Trial populations were: pregnant and postpartum women (11 trials conducted in low‐, middle‐ or high‐income countries (LMHIC); pregnant and postpartum women living with HIV (three trials carried out in one lower middle‐income country); and parents of children under the age of five years (13 trials conducted in LMHIC). Most interventions (18) were delivered via text messages alone, one was delivered through voice calls only, and the rest were delivered through combinations of different communication channels, such as multimedia messages and voice calls. Pregnant and postpartum women TCCMD versus standard care For behaviours, TCCMD may increase exclusive breastfeeding in settings where rates of exclusive breastfeeding are less common (risk ratio (RR) 1.30, 95% confidence intervals (CI) 1.06 to 1.59; low‐certainty evidence), but have little or no effect in settings where almost all women breastfeed (low‐certainty evidence). For use of health services, TCCMD may increase antenatal appointment attendance (odds ratio (OR) 1.54, 95% CI 0.80 to 2.96; low‐certainty evidence); however, the CI encompasses both benefit and harm. The intervention may increase skilled attendants at birth in settings where a lack of skilled attendants at birth is common (though this differed by urban/rural residence), but may make no difference in settings where almost all women already have a skilled attendant at birth (OR 1.00, 95% CI 0.34 to 2.94; low‐certainty evidence). There were uncertain effects on maternal and neonatal mortality and morbidity because the certainty of the evidence was assessed as very low. TCCMD versus non‐digital TCC (e.g. pamphlets) TCCMD may have little or no effect on exclusive breastfeeding (RR 0.92, 95% CI 0.79 to 1.07; low‐certainty evidence). TCCMD may reduce 'any maternal health problem' (RR 0.19, 95% CI 0.04 to 0.79) and 'any newborn health problem' (RR 0.52, 95% CI 0.25 to 1.06) reported up to 10 days postpartum (low‐certainty evidence), though the CI for the latter includes benefit and harm. The effect on health service use is unknown due to a lack of studies. TCCMD versus digital non‐targeted communication No studies reported behavioural, health, or well‐being outcomes for this comparison. For use of health services, there are uncertain effects for the presence of a skilled attendant at birth due to very low‐certainty evidence, and the intervention may make little or no difference to attendance for antenatal influenza vaccination (RR 1.05, 95% CI 0.71 to 1.58), though the CI encompasses both benefit and harm (low‐certainty evidence). Pregnant and postpartum women living with HIV TCCMD versus standard care For behaviours, TCCMD may make little or no difference to maternal and infant adherence to antiretroviral (ARV) therapy (low‐certainty evidence). For health service use, TCC mobile telephone reminders may increase use of antenatal care slightly (mean difference (MD) 1.5, 95% CI –0.36 to 3.36; low‐certainty evidence). The effect on the proportion of births occurring in a health facility is uncertain due to very low‐certainty evidence. For health and well‐being outcomes, there was an uncertain intervention effect on neonatal death or stillbirth, and infant HIV due to very low‐certainty evidence. No studies reported on maternal mortality or morbidity. TCCMD versus non‐digital TCC The effect is unknown due to lack of studies reporting this comparison. TCCMD versus digital non‐targeted communication TCCMD may increase infant ARV/prevention of mother‐to‐child transmission treatment adherence (RR 1.26, 95% CI 1.07 to 1.48; low‐certainty evidence). The effect on other outcomes is unknown due to lack of studies. Parents of children aged less than five years No studies reported on correct treatment, nutritional, or health outcomes. TCCMD versus standard care Based on 10 trials, TCCMD may modestly increase health service use (vaccinations and HIV care) (RR 1.21, 95% CI 1.08 to 1.34; low‐certainty evidence); however, the effect estimates varied widely between studies. TCCMD versus non‐digital TCC TCCMD may increase attendance for vaccinations (RR 1.13, 95% CI 1.00 to 1.28; low‐certainty evidence), and may make little or no difference to oral hygiene practices (low‐certainty evidence). TCCMD versus digital non‐targeted communication TCCMD may reduce attendance for vaccinations, but the CI encompasses both benefit and harm (RR 0.63, 95% CI 0.33 to 1.20; low‐certainty evidence). No trials in any population reported data on unintended consequences. Authors' conclusions The effect of TCCMD for most outcomes is uncertain. There may be improvements for some outcomes using targeted communication but these findings were of low certainty. High‐quality, adequately powered trials and cost‐effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCCMD. Future studies should measure potential unintended consequences, such as partner violence or breaches of confidentiality., Plain language summary Communicating to pregnant woman and parents through their mobile devices to improve maternal, neonatal, and child health Aim of this review We assessed the effect of sending targeted messages by mobile devices to pregnant women and parents of young children about health and healthcare services. Key messages There are gaps in the evidence regarding the effects of targeted messages by mobile devices to pregnant women and parents of young children about health and healthcare services. Some of these messages may improve some people's health and their use of health services, but others may make little or no difference. The existing evidence is mostly of low or very low certainty. What was studied in the review? Targeted client communication (TCC) is an intervention in which the health system sends information to particular people, based on their health status or other factors specific to that population group. Common types of TCC are text messages reminding people to attend appointments or that offer healthcare information and support. Our review assessed whether TCC can change pregnant women's and parents' behaviour, health service use, health, and well‐being. What happens when pregnant women receive targeted messages by mobile device? Compared to women who get no messages Women may breastfeed more in settings where exclusive breastfeeding is not common. They may also go to more antenatal care appointments. They may use skilled birth attendants more where this is less common. We do not know if the messages affect women's or babies' health because the certainty of the evidence is very low. Compared to women who get messages sent in other ways Women and newborns may have fewer health problems during the first 10 days after birth. The messages may make little or no difference to the number of women who breastfeed. We do not know if they make women use more health services. Compared to women who get untargeted messages The messages may make little or no difference to whether women get influenza vaccines during pregnancy. We do not know if the messages affect women's or babies' health or lead women to use skilled birth attendants more because the evidence is lacking or of very low certainty. What happens when pregnant women living with HIV receive targeted messages by mobile device? Compared to women who get no messages Women may go to slightly more antenatal care appointments. We do not know whether the messages lead more women to give birth in a health facility or improve babies' health because the evidence is of very low certainty. The messages may make little or no difference to whether pregnant women and babies follow antiretroviral (ARV) treatment (used to treat HIV) according to plan. We do not know if the messages affect women's health because the evidence is missing. Compared to women who get messages sent in other ways We do not know what the effect of these messages is because we lack evidence. Compared to women who get untargeted messages More parents may follow their babies' ARV treatment according to plan. We do not know if the messages improve women's or babies' health or their use of services because the evidence is missing. What happens when parents of young children receive targeted messages by mobile device? Compared to parents who get no messages More parents may take their children to healthcare services such as vaccination appointments. But we do not know if the messages improve children's health or their health behaviour because the evidence is missing. Compared to parents who get messages sent in other ways Slightly more parents may take their children to vaccination appointments. The messages may make little or no difference to children's toothbrushing habits. We do not know if the messages affect children's health because the evidence is missing. Compared to parents who get untargeted messages Fewer parents may take their children to vaccination appointments, but this evidence is mixed. We do not know if the messages affect children's health due to lack of evidence. How up‐to‐date is this review? We searched for studies published up to August 2017. We carried out a search update in July 2019 and relevant studies are reported in the 'Characteristics of studies awaiting classification' section.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To answer the clinical question: ‘what analgesic medicine shall I prescribe this patient with chronic low back pain to reduce their pain?’.The objectives are to determine the analgesic effects, safety, effect on function, and relative rank according to analgesic effect, safety and effect on function of a single course of opioid analgesics, NSAIDs or paracetamol or combinations of these medicines. Refereed/Peer-reviewed

ObjectiveTo determine whether there is a relationship between physical growth and development, as determined by markers of biological maturation, and musculoskeletal conditions in adolescents.DesignSystematic review.Data sourcesElectronic databases (PubMed, EMBASE and the Cumulative Index to Nursing and Allied Health Literature) were searched up to 6 September 2017.Eligibility criteria for selecting studiesStudies that evaluated the association between biological maturation or growth and musculoskeletal conditions in adolescents (chronological age 10–19 years).ResultsFrom 20 361 titles identified by the searches, 511 full-text articles were retrieved and assessed for eligibility; 56 studies, all at high risk of bias, evaluating the relationship between maturation and/or growth and musculoskeletal conditions were included. A total of 208 estimates of association were identified across the included studies, which generally indicated no association or an unclear association between maturation, growth and musculoskeletal conditions.Summary/ConclusionsWhile the relationship between maturation, growth and musculoskeletal conditions remains plausible, the available evidence is not supportive. The current body of knowledge is at high risk of bias, which impedes our ability to establish whether biological maturity and growth are independent risk factors for musculoskeletal conditions.

Background The widespread use of mobile technologies can potentially expand the use of telemedicine approaches to facilitate communication between healthcare providers, this might increase access to specialist advice and improve patient health outcomes. Objectives To assess the effects of mobile technologies versus usual care for supporting communication and consultations between healthcare providers on healthcare providers' performance, acceptability and satisfaction, healthcare use, patient health outcomes, acceptability and satisfaction, costs, and technical difficulties. Search methods We searched CENTRAL, MEDLINE, Embase and three other databases from 1 January 2000 to 22 July 2019. We searched clinical trials registries, checked references of relevant systematic reviews and included studies, and contacted topic experts. Selection criteria Randomised trials comparing mobile technologies to support healthcare provider to healthcare provider communication and consultations compared with usual care. Data collection and analysis We followed standard methodological procedures expected by Cochrane and EPOC. We used the GRADE approach to assess the certainty of the evidence. Main results We included 19 trials (5766 participants when reported), most were conducted in high‐income countries. The most frequently used mobile technology was a mobile phone, often accompanied by training if it was used to transfer digital images. Trials recruited participants with different conditions, and interventions varied in delivery, components, and frequency of contact. We judged most trials to have high risk of performance bias, and approximately half had a high risk of detection, attrition, and reporting biases. Two studies reported data on technical problems, reporting few difficulties. Mobile technologies used by primary care providers to consult with hospital specialists We assessed the certainty of evidence for this group of trials as moderate to low. Mobile technologies: ‐ probably make little or no difference to primary care providers following guidelines for people with chronic kidney disease (CKD; 1 trial, 47 general practices, 3004 participants); ‐ probably reduce the time between presentation and management of individuals with skin conditions, people with symptoms requiring an ultrasound, or being referred for an appointment with a specialist after attending primary care (4 trials, 656 participants); ‐ may reduce referrals and clinic visits among people with some skin conditions, and increase the likelihood of receiving retinopathy screening among people with diabetes, or an ultrasound in those referred with symptoms (9 trials, 4810 participants when reported); ‐ probably make little or no difference to patient‐reported quality of life and health‐related quality of life (2 trials, 622 participants) or to clinician‐assessed clinical recovery (2 trials, 769 participants) among individuals with skin conditions; ‐ may make little or no difference to healthcare provider (2 trials, 378 participants) or participant acceptability and satisfaction (4 trials, 972 participants) when primary care providers consult with dermatologists; ‐ may make little or no difference for total or expected costs per participant for adults with some skin conditions or CKD (6 trials, 5423 participants). Mobile technologies used by emergency physicians to consult with hospital specialists about people attending the emergency department We assessed the certainty of evidence for this group of trials as moderate. Mobile technologies: ‐ probably slightly reduce the consultation time between emergency physicians and hospital specialists (median difference −12 minutes, 95% CI −19 to −7; 1 trial, 345 participants); ‐ probably reduce participants’ length of stay in the emergency department by a few minutes (median difference −30 minutes, 95% CI −37 to −25; 1 trial, 345 participants). We did not identify trials that reported on providers' adherence, participants’ health status and well‐being, healthcare provider and participant acceptability and satisfaction, or costs. Mobile technologies used by community health workers or home‐care workers to consult with clinic staff We assessed the certainty of evidence for this group of trials as moderate to low. Mobile technologies: ‐ probably make little or no difference in the number of outpatient clinic and community nurse consultations for participants with diabetes or older individuals treated with home enteral nutrition (2 trials, 370 participants) or hospitalisation of older individuals treated with home enteral nutrition (1 trial, 188 participants); ‐ may lead to little or no difference in mortality among people living with HIV (RR 0.82, 95% CI 0.55 to 1.22) or diabetes (RR 0.94, 95% CI 0.28 to 3.12) (2 trials, 1152 participants); ‐ may make little or no difference to participants' disease activity or health‐related quality of life in participants with rheumatoid arthritis (1 trial, 85 participants); ‐ probably make little or no difference for participant acceptability and satisfaction for participants with diabetes and participants with rheumatoid arthritis (2 trials, 178 participants). We did not identify any trials that reported on providers' adherence, time between presentation and management, healthcare provider acceptability and satisfaction, or costs. Authors' conclusions Our confidence in the effect estimates is limited. Interventions including a mobile technology component to support healthcare provider to healthcare provider communication and management of care may reduce the time between presentation and management of the health condition when primary care providers or emergency physicians use them to consult with specialists, and may increase the likelihood of receiving a clinical examination among participants with diabetes and those who required an ultrasound. They may decrease the number of people attending primary care who are referred to secondary or tertiary care in some conditions, such as some skin conditions and CKD. There was little evidence of effects on participants' health status and well‐being, satisfaction, or costs., Plain language summary Using mobile technologies to promote communication and management of care between healthcare professionals What is the aim of this review? We aimed to find out if healthcare workers using mHealth services through their mobile phones or other mobile devices to communicate with other healthcare workers provide quicker access to healthcare, and improve patient health outcomes. We collected and analysed all relevant research and found 19 studies. Key messages Mobile technologies probably slightly decrease the time to deliver health care, as well as the number of face‐to‐face appointments, when compared with usual care, and probably increase the number of people receiving clinical examinations for some conditions, including an eye exam for people with diabetes. Mobile technologies may have little or no impact on healthcare workers' and participants' satisfaction, health status or well‐being. What was studied in the review? Many healthcare workers work alone or have little access to colleagues and specialists. This is a common problem for healthcare workers in rural areas or low‐income countries. One possible solution to this problem is to offer healthcare workers advice and support through mobile technologies that allow healthcare workers to get help from colleagues who are not in the same place. For instance, healthcare workers can contact specialists or colleagues with more experience through a phone or the Internet. Healthcare workers can also use their mobile phones or other mobile devices such as tablets. As more healthcare workers use mobile phones and other devices as part of their work, this could make it particularly easy for them to use mHealth services. What are the main results of the review? We found 19 relevant studies, which included more than 5766 people who needed health care. Sixteen studies were from high‐income countries. Two studies reported on technical problems, reporting few difficulties. When primary healthcare workers use mobile technologies to consult with hospital specialists, they: ‐ probably make little or no difference to whether guidelines are followed for people with chronic kidney disease, or to health status or quality of life of people with psoriasis. ‐ may increase the likelihood of retinopathy screening for people with diabetes, or receiving an ultrasound if referred with symptoms, and may reduce referrals or a visit to the clinic for people with a skin condition or referred for clinic follow‐up for different health problems. ‐ may make little or no difference to healthcare worker or patient satisfaction, or to how much it costs to deliver health care. When emergency doctors use mobile technologies to consult with hospital specialists: ‐ patients are probably managed slightly more quickly. We did not find any studies that looked at the effect of mobile technologies on emergency doctors following guidelines, patients’ health and well‐being, healthcare worker or patient satisfaction, or costs. When community health workers or home‐care workers use mobile technologies to consult with clinic staff, they: ‐ probably make little or no difference to the number of times people with a new diabetes‐related foot ulcer have to see a nurse, or elderly people using tube feeding have to see a nurse or go into hospital. ‐ may make no difference to the number of people living with HIV or diabetes who die; and may make little or no difference to the health status or quality of life of people with rheumatoid arthritis. ‐ probably make little or no difference to the satisfaction of people with diabetes or rheumatoid arthritis. We did not find any studies that looked at the effect of mobile technologies on whether community health workers follow guidelines, how quickly people receive care, healthcare worker satisfaction, costs, or technical difficulties. How up‐to‐date is this review? We searched for studies up to 22 July 2019.

Background Uptake of human papillomavirus (HPV) vaccine remains low in many countries, although the bivalent and quadrivalent HPV vaccines given as a three‐dose schedule are effective in the prevention of precancerous lesions of the cervix in women. Simpler immunisation schedules, such as those with fewer doses, might reduce barriers to vaccination, as may programmes that include males. Objectives To evaluate the efficacy, immunogenicity, and harms of different dose schedules and different types of HPV vaccines in females and males. Search methods We conducted electronic searches on 27 September 2018 in Ovid MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library), and Ovid Embase. We also searched the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov (both 27 September 2018), vaccine manufacturer websites, and checked reference lists from an index of HPV studies and other relevant systematic reviews. Selection criteria We included randomised controlled trials (RCTs) with no language restriction. We considered studies if they enrolled HIV‐negative males or females aged 9 to 26 years, or HIV‐positive males or females of any age. Data collection and analysis We used methods recommended by Cochrane. We use the term 'control' to refer to comparator products containing an adjuvant or active vaccine and 'placebo' to refer to products that contain no adjuvant or active vaccine. Most primary outcomes in this review were clinical outcomes. However, for comparisons comparing dose schedules, the included RCTs were designed to measure antibody responses (i.e. immunogenicity) as the primary outcome, rather than clinical outcomes, since it is unethical to collect cervical samples from girls under 16 years of age. We analysed immunogenicity outcomes (i.e. geometric mean titres) with ratios of means, clinical outcomes (e.g. cancer and intraepithelial neoplasia) with risk ratios or rate ratios and, for serious adverse events and deaths, we calculated odds ratios. We rated the certainty of evidence with GRADE. Main results We included 20 RCTs with 31,940 participants. The length of follow‐up in the included studies ranged from seven months to five years. Two doses versus three doses of HPV vaccine in 9‐ to 15‐year‐old females Antibody responses after two‐dose and three‐dose HPV vaccine schedules were similar after up to five years of follow‐up (4 RCTs, moderate‐ to high‐certainty evidence). No RCTs collected clinical outcome data. Evidence about serious adverse events in studies comparing dose schedules was of very low‐certainty owing to imprecision and indirectness (three doses 35/1159; two doses 36/1158; 4 RCTs). One death was reported in the three‐dose group (1/898) and none in the two‐dose group (0/899) (low‐certainty evidence). Interval between doses of HPV vaccine in 9‐ to 14‐year‐old females and males Antibody responses were stronger with a longer interval (6 or 12 months) between the first two doses of HPV vaccine than a shorter interval (2 or 6 months) at up to three years of follow‐up (4 RCTs, moderate‐ to high‐certainty evidence). No RCTs collected data about clinical outcomes. Evidence about serious adverse events in studies comparing intervals was of very low‐certainty, owing to imprecision and indirectness. No deaths were reported in any of the studies (0/1898, 3 RCTs, low‐certainty evidence). HPV vaccination of 10‐ to 26‐year‐old males In one RCT there was moderate‐certainty evidence that quadrivalent HPV vaccine, compared with control, reduced the incidence of external genital lesions (control 36 per 3081 person‐years; quadrivalent 6 per 3173 person‐years; rate ratio 0.16, 95% CI 0.07 to 0.38; 6254 person‐years) and anogenital warts (control 28 per 2814 person‐years; quadrivalent 3 per 2831 person‐years; rate ratio 0.11, 95% CI 0.03 to 0.38; 5645 person‐years). The quadrivalent vaccine resulted in more injection‐site adverse events, such as pain or redness, than control (537 versus 601 per 1000; risk ratio (RR) 1.12, 95% CI 1.06 to 1.18, 3895 participants, high‐certainty evidence). There was very low‐certainty evidence from two RCTs about serious adverse events with quadrivalent vaccine (control 12/2588; quadrivalent 8/2574), and about deaths (control 11/2591; quadrivalent 3/2582), owing to imprecision and indirectness. Nonavalent versus quadrivalent vaccine in 9‐ to 26‐year‐old females and males Three RCTs were included; one in females aged 9‐ to 15‐years (n = 600), one in females aged 16‐ to 26‐years (n = 14,215), and one in males aged 16‐ to 26‐years (n = 500). The RCT in 16‐ to 26‐year‐old females reported clinical outcomes. There was little to no difference in the incidence of the combined outcome of high‐grade cervical epithelial neoplasia, adenocarcinoma in situ, or cervical cancer between the HPV vaccines (quadrivalent 325/6882, nonavalent 326/6871; OR 1.00, 95% CI 0.85 to 1.16; 13,753 participants; high‐certainty evidence). The other two RCTs did not collect data about clinical outcomes. There were slightly more local adverse events with the nonavalent vaccine (905 per 1000) than the quadrivalent vaccine (846 per 1000) (RR 1.07, 95% CI 1.05 to 1.08; 3 RCTs, 15,863 participants; high‐certainty evidence). Comparative evidence about serious adverse events in the three RCTs (nonavalent 243/8234, quadrivalent 192/7629; OR 0.60, 95% CI 0.14 to 2.61) was of low certainty, owing to imprecision and indirectness. HPV vaccination for people living with HIV Seven RCTs reported on HPV vaccines in people with HIV, with two small trials that collected data about clinical outcomes. Antibody responses were higher following vaccination with either bivalent or quadrivalent HPV vaccine than with control, and these responses could be demonstrated to have been maintained for up to 24 months in children living with HIV (low‐certainty evidence). The evidence about clinical outcomes and harms for HPV vaccines in people with HIV is very uncertain (low‐ to very low‐certainty evidence), owing to imprecision and indirectness. Authors' conclusions The immunogenicity of two‐dose and three‐dose HPV vaccine schedules, measured using antibody responses in young females, is comparable. The quadrivalent vaccine probably reduces external genital lesions and anogenital warts in males compared with control. The nonavalent and quadrivalent vaccines offer similar protection against a combined outcome of cervical, vaginal, and vulval precancer lesions or cancer. In people living with HIV, both the bivalent and quadrivalent HPV vaccines result in high antibody responses. For all comparisons of alternative HPV vaccine schedules, the certainty of the body of evidence about serious adverse events reported during the study periods was low or very low, either because the number of events was low, or the evidence was indirect, or both. Post‐marketing surveillance is needed to continue monitoring harms that might be associated with HPV vaccines in the population, and this evidence will be incorporated in future updates of this review. Long‐term observational studies are needed to determine the effectiveness of reduced‐dose schedules against HPV‐related cancer endpoints, and whether adopting these schedules improves vaccine coverage rates., Plain language summary Comparison of different human papillomavirus (HPV) vaccines and the number of doses administered to prevent HPV‐related disease in females and males Human papillomaviruses (HPV) are a group of viruses that infect the skin and mucous membranes. Some types of HPV are sexually transmitted and are common in young people. Most infections will be cleared by the immune system, but some people will experience persistent infection with certain HPV types that go on to cause abnormalities in infected cells. These changes are called 'precancerous' because they can develop into cancers of the cervix, vagina, vulva, anal canal, penis, and head and neck. Infection with other HPV types causes warts in the genital area or around the anus. Vaccination aims to prevent future HPV infections. Three HPV vaccines are in use – a bivalent one (protects against two HPV types), a quadrivalent one (protects against four HPV types), and a nonavalent one (protects against nine HPV types). In women, three doses of the bivalent or the quadrivalent HPV vaccines protect against precancer of the cervix caused by the HPV types contained in the vaccine. Evidence about the nonavalent vaccine, about the effects of the quadrivalent vaccine in males, and about the effects of HPV vaccines in people with HIV infection, has not yet been reviewed thoroughly. Uptake of HPV vaccines remains low in many countries. Simpler vaccine schedules, or giving the vaccine to both girls and boys, could increase the number of people being vaccinated. Trials of HPV vaccines are not always designed to collect data about precancer and cancer, for several reasons. Firstly, HPV vaccine is routinely given before girls become sexually active, and it is not ethical to take specimens from the cervix of girls who have not had sex. Secondly, HPV‐related precancer and cancer are rare and do not develop until years after HPV infection has occurred. Thirdly, participants in a trial will be offered treatment if precancer develops, so progression to cervical cancer would be even rarer, even without vaccination. An international committee of experts states that, in some circumstances, antibody levels (i.e. showing a strong immune system response), can be used to demonstrate protection against cervical and anal cancer. The antibody levels following vaccination in a trial should not be lower than those found in other studies on adults in whom the vaccine has been shown to protect against severe HPV‐related cervical or anal disease. Review question(s) How effective or harmful are different HPV vaccine schedules (i.e. number and timing of doses) and different HPV vaccines in females and males? Main results These results are based on research evidence to 27 September 2018. We analysed 20 studies involving 31,940 people. Studies comparing two doses of HPV vaccine to three doses, or comparing the time interval between doses, focus on immune system responses rather than infection or disease outcomes. Two doses of HPV vaccine result in similar immune system responses to three doses, and a longer interval (up to 12 months) between doses gives a stronger immune system response than a shorter interval. There is insufficient evidence to determine whether there was a difference between the vaccine schedules for serious adverse events and death. In 16‐ to 26‐year‐old men, one study showed evidence of moderate certainty that a quadrivalent HPV vaccine provides better protection against external genital lesions and genital warts than a dummy treatment (control). In 16‐ to 26‐year‐old women, one study showed that the nonavalent and quadrivalent vaccines provide the same levels of protection against cervical, vaginal, and vulval precancer lesions and cancer (high‐certainty evidence). There was evidence that the quadrivalent vaccine resulted in more local adverse events (such as pain, swelling, and redness at the injection site) than a control treatment in males, and that the nonavalent vaccine resulted in more local adverse events than the quadrivalent vaccine in males and females. Evidence about serious adverse events and deaths from studies comparing different HPV vaccine types or dose schedules was of low or very low‐certainty. In people living with HIV, HPV vaccines result in reasonable levels of immune system response, but evidence about their effects on persistent HPV infection or HPV‐related disease outcomes and harms is limited. Certainty of the evidence No major issues were identified with the methodological quality of the studies for the measurements of infection and disease outcomes, or for immune system responses. Our certainty in the evidence about serious harms and deaths across all the studies comparing different HPV vaccines and vaccine schedules is low, either because of their low frequency, or because the evidence is indirect, or both. Evidence graded as high certainty means that we were confident that further research is unlikely to change our findings. Moderate‐certainty evidence means that there is a possibility that further research may have an important effect on our findings, whilst low‐certainty evidence means that our confidence was limited and further research may have an important impact on our findings. Very low‐certainty evidence means that we were uncertain about the result. Conclusion A two‐dose schedule of HPV vaccines in young females results in immune system responses that are comparable with a three‐dose schedule. In males, the quadrivalent HPV vaccine appears to be effective in the prevention of external genital lesions and genital warts. Quadrivalent and nonavalent HPV vaccines in young women result in similar levels of protection against cervical, vaginal, and vulval precancer lesions and cancer. Evidence about the efficacy and harms in people living with HIV is limited. Further long‐term population‐level studies are needed to continue monitoring safety of these vaccines, to determine for how long two doses of vaccine can provide protection against HPV‐related disease, the effect against HPV‐related cancer, and whether a two‐dose immunisation schedule will increase vaccine coverage.

To determine the frequency of red flag signs and symptoms in patients presenting with back pain to the Emergency Department (ED) and association with serious pathologies and investigations performed.This retrospective observational study evaluated consecutive patients presenting with back pain to a Melbourne ED over a 14-month period. Data regarding red flags, patient characteristics, ED-initiated investigations, and diagnoses were extracted from medical records. Prevalence of each red flag and sensitivity, specificity, and likelihood ratios for diagnosing serious spinal or non-spinal pathology were calculated.Analysis was undertaken on 1000 eligible participants with back pain. 69% had red flags. Participants were categorised into diagnostic groups: musculoskeletal (80.6%), serious spinal (3.3%), and serious non-spinal (14.6%) pathologies. A number of red flags had positive likelihood ratios (LR) 5, indicating a higher probability of serious pathology (spinal/non-spinal) including fever (LR + 68.8), tuberculosis history (LR + 13.8), known nephrolithiasis/abdominal aortic aneurysm (LR + 10.2), unexplained weight-loss (LR + 9.2), writhing in pain (LR + 6.9), urinary symptoms (LR + 5.4), and flank pain (LR + 5.2). Red flags with positive LR 5 indicating a higher probability of serious spinal pathology were saddle anaesthesia (LR + 11.0), tuberculosis history (LR + 9.8), intravenous drug-use (LR + 6.9), acute-onset urinary retention (LR + 6.4), and anal tone loss (LR + 6.3).The majority of this study cohort had back pain of benign cause. Some red flags were associated with greater risk of serious pathology, others were not. Further evidence regarding red flags and their association with serious pathology is required, to better inform clinical guidelines.

Summary Background Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages. Methods All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5·0 years, with and without restrictions on age at administration. Benefit–risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria–tetanus–pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1. Findings A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000–100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77–550) excess intussusception deaths (1·4% increase) compared with no vaccination, resulting in a benefit–risk ratio of 369:1 (160:1–895:1). The benefit–risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit–risk ratios. Interpretation Rotavirus vaccines have a favourable benefit–risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits. Funding Bill & Melinda Gates Foundation.

© 2018 2018 American Medical Association. All rights reserved. Importance: Many patients with acute low back pain do not recover with basic first-line care (advice, reassurance, and simple analgesia, if necessary). It is unclear whether intensive patient education improves clinical outcomes for those patients already receiving first-line care. Objective: To determine the effectiveness of intensive patient education for patients with acute low back pain. Design, Setting, and Participants: This randomized, placebo-controlled clinical trial recruited patients from general practices, physiotherapy clinics, and a research center in Sydney, Australia, between September 10, 2013, and December 2, 2015. Trial follow-up was completed in December 17, 2016. Primary care practitioners invited 618 patients presenting with acute low back pain to participate. Researchers excluded 416 potential participants. All of the 202 eligible participants had low back pain of fewer than 6 weeks' duration and a high risk of developing chronic low back pain according to Predicting the Inception of Chronic Pain (PICKUP) Tool, a validated prognostic model. Participants were randomized in a 1:1 ratio to either patient education or placebo patient education. Interventions: All participants received recommended first-line care for acute low back pain from their usual practitioner. Participants received additional 2 × 1-hour sessions of patient education (information on pain and biopsychosocial contributors plus self-management techniques, such as remaining active and pacing) or placebo patient education (active listening, without information or advice). Main Outcomes and Measures: The primary outcome was pain intensity (11-point numeric rating scale) at 3 months. Secondary outcomes included disability (24-point Roland Morris Disability Questionnaire) at 1 week, and at 3, 6, and 12 months. Results: Of 202 participants randomized for the trial, the mean (SD) age of participants was 45 (14.5) years and 103 (51.0%) were female. Retention rates were greater than 90% at all time points. Intensive patient education was not more effective than placebo patient education at reducing pain intensity (3-month mean [SD] pain intensity: 2.1 [2.4] vs 2.4 [2.2]; mean difference at 3 months, -0.3 [95% CI, -1.0 to 0.3]). There was a small effect of intensive patient education on the secondary outcome of disability at 1 week (mean difference, -1.6 points on a 24-point scale [95% CI, -3.1 to -0.1]) and 3 months (mean difference, -1.7 points, [95% CI, -3.2 to -0.2]) but not at 6 or 12 months. Conclusions and Relevance: Adding 2 hours of patient education to recommended first-line care for patients with acute low back pain did not improve pain outcomes. Clinical guideline recommendations to provide complex and intensive support to high-risk patients with acute low back pain may have been premature. Trial Registration: Australian Clinical Trial Registration Number: 12612001180808.

© 2016 Elsevier Ireland Ltd Objective Professional appearance is easily modifiable, and might alter the effects of a clinical encounter. We aimed to determine whether professional attire influences a patient's perception of treatment credibility. Methods We performed a single-blind randomized controlled study on 128 patients with acute non-specific low back pain who were about to receive treatment in primary care. The treating clinician was randomly allocated to wear formal attire (experimental condition) or casual attire (control condition) to the consultation. Clinicians provided a standardized briefing on the rationale behind the patient's forthcoming treatment. Treatment credibility (Credibility and Expectancy Questionnaire) was assessed immediately after this briefing. Results All patients received the experimental or control condition as allocated and provided complete primary outcome data. Formal attire had no effect on perceived treatment credibility (Mean difference between groups 1.2 [95%CI-1.1 to 3.5]). Age was the only significant predictor of treatment credibility; older patients rated treatment credibility higher (Beta = 0.16 [95%CI 0.08 to 0.24]). Conclusion In a trial setting, whether or not a clinician is formally dressed has no effect on perceptions of treatment credibility in patients with acute low back pain. Practice implication Clinicians should dress comfortably without fear of losing credibility.

Low back pain is highly prevalent and places a considerable burden on individuals, their families and communities. This back pain burden is unequally distributed around the world and within populations. Clinicians and researchers addressing back pain should be aware of the cultural, social and political context of back pain patients and how this context can influence pain perception, disability and health care use. Culture, which influences the beliefs and behaviour of individuals within a social group, could be considered an important contributor to the unequal distribution of back pain. However, there is paucity of high-quality research exploring the influence of culture on the experience and management of back pain. Further development and testing of specific tools, assessment methods and communication strategies are needed to improve our understanding of how cultural practices, values and identifications affect those dealing with back pain.

ResumoIntroduçãoA prevalência de lombalgia deverá aumentar em todo o mundo com o envelhecimento da população, mas sua prevalência em idosos não é clara, principalmente, em países em desenvolvimento.ObjetivoEstimar a prevalência de lombalgia em idosos brasileiros.MétodosForam feitas buscas eletrônicas nas bases de dados SciELO, Lilacs, Medline, Embase e Cinahl, bem como uma busca manual de estudos que investigaram a prevalência de lombalgia em idosos brasileiros com 60 anos ou mais. Dois revisores independentes selecionaram os estudos que atenderam aos critérios de inclusão, avaliaram o risco de viés de cada estudo incluído e extraíram os dados relevantes. Foi feita uma metanálise quando houve homogeneidade suficiente entre os estudos e o sistema Grade foi usado para resumir a qualidade geral das evidências.ResultadosForam incluídos 16 estudos originais com um total de 28.448 participantes. Foram obtidos dados de prevalência pontual e prevalência no período da lombalgia. Foi feita metanálise de 13 estudos que reportaram a prevalência pontual. A prevalência pontual agrupada de lombalgia foi de 25% = 15% (IC 95% 18 a 32). Outros três estudos investigaram a prevalência no período: em uma semana (IC 95% 13 a 18); em seis meses= 43% (95% IC 42 a 44); e em 12 meses = 13% (IC 95% 11 a 16). Foram feitas análises sensitivas da prevalência pontual e a exclusão de estudos com baixa qualidade metodológica aumentou a prevalência estimada de lombalgia.ConclusãoEvidências de qualidade moderada mostram que em um dado momento no tempo um em cada quatro idosos brasileiros apresenta lombalgia. Esta foi a primeira revisão sistemática que investigou dados nacionais sobre a prevalência de lombalgia em pessoas idosas, contribuindo com importantes evidências clínicas e epidemiológicas para os gestores e profissionais de saúde.AbstractIntroductionPrevalence of low back pain (LBP) is expected to increase worldwide with ageing of the population but its prevalence in older people is not clear, mainly in developing countries.ObjectiveTo estimate the prevalence of LBP in older Brazilians.MethodsElectronic searches on SciELO, Lilacs, Medline, Embase and Cinahl, as well as hand‐searching identified studies investigating prevalence of LBP in older Brazilians aged 60 years or older. Two independent reviewers selected studies fulfilling the inclusion criteria, assessed risk of bias for each included study and extracted relevant data. Meta‐analysis was conducted when enough homogeneity allowed and the GRADE system was used to summarize the overall quality of the evidence.ResultsSixteen studies were included with a total of 28,448 participants. Data from point‐ and period‐prevalence of LBP were obtained. Meta‐analysis was conducted for 13 studies reporting point‐prevalence. Pooled point‐prevalence of LBP was 25.0% (95% CI 18.0 to 32.0). Other three studies investigated period‐prevalence: one‐week prevalence = 15.0% (95% CI 13.0 to 18.0); six‐month prevalence = 43.0% (95% CI 42.0 to 44.0); and 12‐month prevalence = 13.0% (95% CI 11.0 to 16.0). Sensitivity analyses were performed for point‐prevalence and exclusion of studies with poorer methodological quality tended to increase the estimated prevalence of LBP.ConclusionModerate‐quality evidence show that at any point in time one in four older Brazilians suffers from LBP. This is the first systematic review investigating nationwide data on the prevalence of LBP in older people and contributes important clinical and epidemiological evidence for policymakers and health professionals.

Introduction Climate change and rapid population ageing are significant public health challenges. Understanding which health problems are affected by temperature is important for preventing heat and cold-related deaths and illnesses, particularly in the elderly. Here we present a systematic review and meta-analysis on the effects of ambient hot and cold temperature (excluding heat/cold wave only studies) on elderly (65 + years) mortality and morbidity. Methods Time-series or case-crossover studies comprising cause-specific cases of elderly mortality (n = 3,933,398) or morbidity (n = 12,157,782) were pooled to obtain a percent change (%) in risk for temperature exposure on cause-specific disease outcomes using a random-effects meta-analysis. Results A 1 °C temperature rise increased cardiovascular (3.44%, 95% CI 3.10–3.78), respiratory (3.60%, 3.18–4.02), and cerebrovascular (1.40%, 0.06–2.75) mortality. A 1 °C temperature reduction increased respiratory (2.90%, 1.84–3.97) and cardiovascular (1.66%, 1.19–2.14) mortality. The greatest risk was associated with cold-induced pneumonia (6.89%, 20–12.99) and respiratory morbidity (4.93% 1.54–8.44). A 1 °C temperature rise increased cardiovascular, respiratory, diabetes mellitus, genitourinary, infectious disease and heat-related morbidity. Discussion Elevated risks for the elderly were prominent for temperature-induced cerebrovascular, cardiovascular, diabetes, genitourinary, infectious disease, heat-related, and respiratory outcomes. These risks will likely increase with climate change and global ageing., Highlights • Heat and cold exposure elevates elderly risk of cardiovascular and cerebrovascular deaths and respiratory deaths and morbidity. • Climate change and ageing will likely increase the risk of diabetes, renal, infectious disease and heat-induced morbidity. • Temperature risks for elderly populations in Africa, Middle East, Asia and South America are under-represented. We applied a rigorous search strategy on three relevant databases following the PRISMA protocol. The search retrieved 18 mortality, and 30 morbidity publications eligible for meta-analysis, representing 3,933,398 deaths and 12,157,782 morbidity cases. Robust risk estimates were calculated for a wide range of temperature-sensitive health outcomes in the elderly. Temperature was found to significantly elevate cerebrovascular, cardiovascular, diabetes, genitourinary, and especially respiratory mortality or morbidity risks in the elderly. This study highlights considerable adverse health risks from temperature exposure in a large vulnerable population and provides impetus for climate change policy to address these risks.