Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

BACKGROUND: Although many people infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) experience no or mild symptoms, some individuals can develop severe illness and may die, particularly older people and those with underlying medical problems. Providing evidence-based interventions to prevent SARS-CoV-2 infection has become more urgent with the potential psychological toll imposed by the coronavirus disease 2019 (COVID-19) pandemic. Controlling exposures to occupational hazards is the fundamental method of protecting workers. When it comes to the transmission of viruses, workplaces should first consider control measures that can potentially have the most significant impact. According to the hierarchy of controls, one should first consider elimination (and substitution), then engineering controls, administrative controls, and lastly, personal protective equipment. This is the first update of a Cochrane review published 6 May 2022, with one new study added. OBJECTIVES: To assess the benefits and harms of interventions in non-healthcare-related workplaces aimed at reducing the risk of SARS-CoV-2 infection compared to other interventions or no intervention. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science Core Collections, Cochrane COVID-19 Study Register, World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and medRxiv to 13 April 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies of interventions. We included adult workers, both those who come into close contact with clients or customers (e.g. public-facing employees, such as cashiers or taxi drivers), and those who do not, but who could be infected by coworkers. We excluded studies involving healthcare workers. We included any intervention to prevent or reduce workers' exposure to SARS-CoV-2 in the workplace, defining categories of intervention according to the hierarchy of hazard controls (i.e. elimination; engineering controls; administrative controls; personal protective equipment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were incidence rate of SARS-CoV-2 infection (or other respiratory viruses), SARS-CoV-2-related mortality, adverse events, and absenteeism from work. Our secondary outcomes were all-cause mortality, quality of life, hospitalisation, and uptake, acceptability, or adherence to strategies. We used the Cochrane RoB 2 tool to assess risk of bias, and GRADE methods to evaluate the certainty of evidence for each outcome. MAIN RESULTS: We identified 2 studies including a total of 16,014 participants. Elimination-of-exposure interventions We included one study examining an intervention that focused on elimination of hazards, which was an open-label, cluster-randomised, non-inferiority trial, conducted in England in 2021. The study compared standard 10-day self-isolation after contact with an infected person to a new strategy of daily rapid antigen testing and staying at work if the test is negative (test-based attendance). The trialists hypothesised that this would lead to a similar rate of infections, but lower COVID-related absence. Staff (N = 11,798) working at 76 schools were assigned to standard isolation, and staff (N = 12,229) working at 86 schools were assigned to the test-based attendance strategy. The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of symptomatic polymerase chain reaction (PCR)-positive SARS-CoV-2 infection (rate ratio (RR) 1.28, 95% confidence interval (CI) 0.74 to 2.21; 1 study; very low-certainty evidence). The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of any PCR-positive SARS-CoV-2 infection (RR 1.35, 95% CI 0.82 to 2.21; 1 study; very low-certainty evidence). COVID-related absenteeism rates were 3704 absence days in 566,502 days-at-risk (6.5 per 1000 working days) in the control group and 2932 per 539,805 days-at-risk (5.4 per 1000 working days) in the intervention group (RR 0.83, 95% CI 0.55 to 1.25). We downgraded the certainty of the evidence to low due to imprecision. Uptake of the intervention was 71% in the intervention group, but not reported for the control intervention. The trial did not measure our other outcomes of SARS-CoV-2-related mortality, adverse events, all-cause mortality, quality of life, or hospitalisation. We found seven ongoing studies using elimination-of-hazard strategies, six RCTs and one non-randomised trial. Administrative control interventions We found one ongoing RCT that aims to evaluate the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in preventing COVID-19 infection and reducing disease severity. Combinations of eligible interventions We included one non-randomised study examining a combination of elimination of hazards, administrative controls, and personal protective equipment. The study was conducted in two large retail companies in Italy in 2020. The study compared a safety operating protocol, measurement of body temperature and oxygen saturation upon entry, and a SARS-CoV-2 test strategy with a minimum activity protocol. Both groups received protective equipment. All employees working at the companies during the study period were included: 1987 in the intervention company and 1798 in the control company. The study did not report an outcome of interest for this systematic review. Other intervention categories We did not find any studies in this category. AUTHORS' CONCLUSIONS: We are uncertain whether a test-based attendance policy affects rates of PCR-positive SARS-CoV-2 infection (any infection; symptomatic infection) compared to standard 10-day self-isolation amongst school and college staff. A test-based attendance policy may result in little to no difference in absenteeism rates compared to standard 10-day self-isolation. The non-randomised study included in our updated search did not report any outcome of interest for this Cochrane review. As a large part of the population is exposed in the case of a pandemic, an apparently small relative effect that would not be worthwhile from the individual perspective may still affect many people, and thus become an important absolute effect from the enterprise or societal perspective. The included RCT did not report on any of our other primary outcomes (i.e. SARS-CoV-2-related mortality and adverse events). We identified no completed studies on any other interventions specified in this review; however, eight eligible studies are ongoing. More controlled studies are needed on testing and isolation strategies, and working from home, as these have important implications for work organisations.

Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a psychiatric diagnosis increasingly used in adults. The recommended first-line pharmacological treatment is central nervous system (CNS) stimulants, such as methylphenidate, but uncertainty remains about its benefits and harms. OBJECTIVES: To assess the beneficial and harmful effects of extended-release formulations of methylphenidate in adults diagnosed with ADHD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases and four clinical trial registries up to February 2021. We searched 12 drug regulatory databases for clinical trial data up to 13 May 2020. In addition, we cross-referenced all available trial identifiers, handsearched reference lists, searched pharmaceutical company databases, and contacted trial authors. SELECTION CRITERIA: Randomised, double-blind, parallel-group trials comparing extended-release methylphenidate formulations at any dose versus placebo and other ADHD medications in adults diagnosed with ADHD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We assessed dichotomous outcomes as risk ratios (RRs), and rating scales and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs). We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We meta-analysed the data using a random-effects model. We assessed three design characteristics that may impair the trial results' 'generalisability'; exclusion of participants with psychiatric comorbidity; responder selection based on previous experience with CNS stimulants; and risk of withdrawal effects. Our prespecified primary outcomes were functional outcomes, self-rated ADHD symptoms, and serious adverse events. Our secondary outcomes included quality of life, ADHD symptoms rated by investigators and by peers such as family members, cardiovascular variables, severe psychiatric adverse events, and other adverse events. MAIN RESULTS: We included 24 trials (5066 participants), of which 21 reported outcome data for this review. We also identified one ongoing study. We included documents from six drug regulatory agencies covering eight trials. Twenty-one trials had an outpatient setting and three were conducted in prisons. They were primarily conducted in North America and Europe. The median participant age was 36 years. Twelve trials (76% of participants) were industry-sponsored, four (14% of participants) were publicly funded with industry involvement, seven (10% of participants) were publicly funded, and one had unclear funding. The median trial duration was eight weeks. One trial was rated at overall unclear risk of bias and 20 trials were rated at overall high risk of bias, primarily due to unclear blinding of participants and investigators, attrition bias, and selective outcome reporting. All trials were impaired in at least one of the three design characteristics related to 'generalisability'; for example, they excluded participants with psychiatric comorbidity such as depression or anxiety, or included participants only with a previous positive response to methylphenidate, or similar drugs. This may limit the trials' usefulness for clinical practice, as they may overestimate the benefits and underestimate the harms. Extended-release methylphenidate versus placebo (up to 26 weeks) For the primary outcomes, we found very low-certainty evidence that methylphenidate had no effect on 'days missed at work' at 13-week follow-up (mean difference (MD) -0.15 days, 95% confidence interval (CI) -2.11 to 1.81; 1 trial, 409 participants) or serious adverse events (risk ratio (RR) 1.43, CI 95% CI 0.85 to 2.43; 14 trials, 4078 participants), whereas methylphenidate improved self-rated ADHD symptoms (small-to-moderate effect; SMD -0.37, 95% CI -0.43 to -0.30; 16 trials, 3799 participants). For secondary outcomes, we found very low-certainty evidence that methylphenidate improved self-rated quality of life (small effect; SMD -0.15, 95% CI -0.25 to -0.05; 6 trials, 1888 participants), investigator-rated ADHD symptoms (small-to-moderate effect; SMD -0.42, 95% CI -0.49 to -0.36; 18 trials, 4183 participants), ADHD symptoms rated by peers such as family members (small-to-moderate effect; SMD -0.31, 95% CI -0.48 to -0.14; 3 trials, 1005 participants), and increased the risk of experiencing any adverse event (RR 1.27, 95% CI 1.19 to 1.37; 14 trials, 4214 participants). We rated the certainty of the evidence as 'very low' for all outcomes, primarily due to high risk of bias and 'indirectness of the evidence'. One trial (419 participants) had follow-up at 52 weeks and two trials (314 participants) included active comparators, hence long-term and comparative evidence is limited. AUTHORS' CONCLUSIONS: We found very low-certainty evidence that extended-release methylphenidate compared to placebo improved ADHD symptoms (small-to-moderate effects) measured on rating scales reported by participants, investigators, and peers such as family members. Methylphenidate had no effect on 'days missed at work' or serious adverse events, the effect on quality of life was small, and it increased the risk of several adverse effects. We rated the certainty of the evidence as 'very low' for all outcomes, due to high risk of bias, short trial durations, and limitations to the generalisability of the results. The benefits and harms of extended-release methylphenidate therefore remain uncertain.

Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care.

BACKGROUND: Acute respiratory infections (ARIs) are by far the most common reason for prescribing an antibiotic in primary care, even though the majority of ARIs are of viral or non-severe bacterial aetiology. It follows that in many cases antibiotic use will not be beneficial to a patient's recovery but may expose them to potential side effects. Furthermore, limiting unnecessary antibiotic use is a key factor in controlling antibiotic resistance. One strategy to reduce antibiotic use in primary care is point-of-care biomarkers. A point-of-care biomarker (test) of inflammation identifies part of the acute phase response to tissue injury regardless of the aetiology (infection, trauma, or inflammation) and may be used as a surrogate marker of infection, potentially assisting the physician in the clinical decision whether to use an antibiotic to treat ARIs. Biomarkers may guide antibiotic prescription by ruling out a serious bacterial infection and help identify patients in whom no benefit from antibiotic treatment can be anticipated. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of point-of-care biomarker tests of inflammation to guide antibiotic treatment in people presenting with symptoms of acute respiratory infections in primary care settings regardless of patient age. SEARCH METHODS: We searched CENTRAL (2022, Issue 6), MEDLINE (1946 to 14 June 2022), Embase (1974 to 14 June 2022), CINAHL (1981 to 14 June 2022), Web of Science (1955 to 14 June 2022), and LILACS (1982 to 14 June 2022). We also searched three trial registries (10 December 2021) for completed and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in primary care patients with ARIs that compared the use of point-of-care biomarkers with standard care. We included trials that randomised individual participants, as well as trials that randomised clusters of patients (cluster-RCTs). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the following primary outcomes: number of participants given an antibiotic prescription at index consultation and within 28 days follow-up; participant recovery within seven days follow-up; and total mortality within 28 days follow-up. We assessed risk of bias using the Cochrane risk of bias tool and the certainty of the evidence using GRADE. We used random-effects meta-analyses when feasible. We further analysed results with considerable heterogeneity in prespecified subgroups of individual and cluster-RCTs. MAIN RESULTS: We included seven new trials in this update, for a total of 13 included trials. Twelve trials (10,218 participants in total, 2335 of which were children) evaluated a C-reactive protein point-of-care test, and one trial (317 adult participants) evaluated a procalcitonin point-of-care test. The studies were conducted in Europe, Russia, and Asia. Overall, the included trials had a low or unclear risk of bias. However all studies were open-labelled, thereby introducing high risk of bias due to lack of blinding. The use of C-reactive protein point-of-care tests to guide antibiotic prescription likely reduces the number of participants given an antibiotic prescription, from 516 prescriptions of antibiotics per 1000 participants in the control group to 397 prescriptions of antibiotics per 1000 participants in the intervention group (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69 to 0.86; 12 trials, 10,218 participants; I² = 79%; moderate-certainty evidence).  Overall, use of C-reactive protein tests also reduce the number of participants given an antibiotic prescription within 28 days follow-up (664 prescriptions of antibiotics per 1000 participants in the control group versus 538 prescriptions of antibiotics per 1000 participants in the intervention group) (RR 0.81, 95% CI 0.76 to 0.86; 7 trials, 5091 participants; I² = 29; high-certainty evidence). The prescription of antibiotics as guided by C-reactive protein tests likely does not reduce the number of participants recovered, within seven or 28 days follow-up (567 participants recovered within seven days follow-up per 1000 participants in the control group versus 584 participants recovered within seven days follow-up per 1000 participants in the intervention group) (recovery within seven days follow-up: RR 1.03, 95% CI 0.96 to 1.12; I² = 0%; moderate-certainty evidence) (recovery within 28 days follow-up: RR 1.02, 95% CI 0.79 to 1.32; I² = 0%; moderate-certainty evidence). The use of C-reactive protein tests may not increase total mortality within 28 days follow-up, from 1 death per 1000 participants in the control group to 0 deaths per 1000 participants in the intervention group (RR 0.53, 95% CI 0.10 to 2.92; I² = 0%; low-certainty evidence). We are uncertain as to whether procalcitonin affects any of the primary or secondary outcomes because there were few participants, thereby limiting the certainty of evidence. We assessed the certainty of the evidence as moderate to high according to GRADE for the primary outcomes for C-reactive protein test, except for mortality, as there were very few deaths, thereby limiting the certainty of the evidence. AUTHORS' CONCLUSIONS: The use of C-reactive protein point-of-care tests as an adjunct to standard care likely reduces the number of participants given an antibiotic prescription in primary care patients who present with symptoms of acute respiratory infection. The use of C-reactive protein point-of-care tests likely does not affect recovery rates. It is unlikely that further research will substantially change our conclusion regarding the reduction in number of participants given an antibiotic prescription, although the size of the estimated effect may change.  The use of C-reactive protein point-of-care tests may not increase mortality within 28 days follow-up, but there were very few events. Studies that recorded deaths and hospital admissions were performed in children from low- and middle-income countries and older adults with comorbidities.  Future studies should focus on children, immunocompromised individuals, and people aged 80 years and above with comorbidities. More studies evaluating procalcitonin and potential new biomarkers as point-of-care tests used in primary care to guide antibiotic prescription are needed.  Furthermore, studies are needed to validate C-reactive protein decision algorithms, with a specific focus on potential age group differences.

Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

BACKGROUND: Although many people infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) experience no or mild symptoms, some individuals can develop severe illness and may die, particularly older people and those with underlying medical problems. Providing evidence-based interventions to prevent SARS-CoV-2 infection has become more urgent with the spread of more infectious SARS-CoV-2 variants of concern (VoC), and the potential psychological toll imposed by the coronavirus disease 2019 (COVID-19) pandemic.   Controlling exposures to occupational hazards is the fundamental method of protecting workers. When it comes to the transmission of viruses, such as SARS-CoV-2, workplaces should first consider control measures that can potentially have the most significant impact. According to the hierarchy of controls, one should first consider elimination (and substitution), then engineering controls, administrative controls, and lastly, personal protective equipment (PPE). OBJECTIVES: To assess the benefits and harms of interventions in non-healthcare-related workplaces to reduce the risk of SARS-CoV-2 infection relative to other interventions, or no intervention. SEARCH METHODS: We searched MEDLINE, Embase, Web of Science, Cochrane COVID-19 Study Register, the Canadian Centre for Occupational Health and Safety (CCOHS), Clinicaltrials.gov, and the International Clinical Trials Registry Platform to 14 September 2021. We will conduct an update of this review in six months. SELECTION CRITERIA: We included randomised control trials (RCT) and planned to include non-randomised studies of interventions. We included adult workers, both those who come into close contact with clients or customers (e.g. public-facing employees, such as cashiers or taxi drivers), and those who do not, but who could be infected by co-workers. We excluded studies involving healthcare workers. We included any intervention to prevent or reduce workers' exposure to SARS-CoV-2 in the workplace, defining categories of intervention according to the hierarchy of hazard controls, i.e. elimination; engineering controls; administrative controls; personal protective equipment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were incidence rate of SARS-CoV-2 infection (or other respiratory viruses), SARS-CoV-2-related mortality, adverse events, and absenteeism from work. Our secondary outcomes were all-cause mortality, quality of life, hospitalisation, and uptake, acceptability, or adherence to strategies. We used the Cochrane RoB 2 tool to assess the risk of bias, and GRADE methods to assess the certainty of evidence for each outcome. MAIN RESULTS: Elimination of exposure interventions We included one study examining an intervention that focused on elimination of hazards. This study is an open-label, cluster-randomised, non-inferiority trial, conducted in England in 2021. The study compared standard 10-day self-isolation after contact with an infected person to a new strategy of daily rapid antigen testing and staying at work if the test is negative (test-based attendance). The trialists hypothesised that this would lead to a similar rate of infections, but lower COVID-related absence. Staff (N = 11,798) working at 76 schools were assigned to standard isolation, and staff (N = 12,229) at 86 schools to the test-based attendance strategy.  The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of symptomatic PCR-positive SARS-COV-2 infection rate ratio ((RR) 1.28, 95% confidence interval (CI) 0.74 to 2.21; 1 study, very low-certainty evidence)). The results between test-based attendance and standard 10-day self-isolation were inconclusive for the rate of any PCR-positive SARS-COV-2 infection (RR 1.35, 95% CI 0.82 to 2.21; 1 study, very low-certainty evidence). COVID-related absenteeism rates were 3704 absence days in 566,502 days-at-risk (6.5 per 1000 days at risk) in the control group and 2932 per 539,805 days-at-risk (5.4 per 1000 days at risk) in the intervention group (RR 0.83; 95% CI 0.55 to 1.25). The certainty of the evidence was downgraded to low, due to imprecision. Uptake of the intervention was 71 % in the intervention group, but not reported for the control intervention.  The trial did not measure other outcomes, SARS-CoV-2-related mortality, adverse events, all-cause mortality, quality of life, and hospitalisation. We found one ongoing RCT about screening in schools, using elimination of hazard strategies. Personal protective equipment We found one ongoing non-randomised study on the effects of closed face shields to prevent COVID-19 transmission. Other intervention categories We did not find studies in the other intervention categories. AUTHORS' CONCLUSIONS: We are uncertain whether a test-based attendance policy affects rates of PCR-postive SARS-CoV-2 infection (any infection; symptomatic infection) compared to standard 10-day self-isolation amongst school and college staff. Test-based attendance policy may result in little to no difference in absence rates compared to standard 10-day self-isolation. As a large part of the population is exposed in the case of a pandemic, an apparently small relative effect that would not be worthwhile from the individual perspective may still affect many people, and thus, become an important absolute effect from the enterprise or societal perspective.  The included study did not report on any other primary outcomes of our review, i.e. SARS-CoV-2-related mortality and adverse events. No completed studies were identified on any other interventions specified in this review, but two eligible studies are ongoing. More controlled studies are needed on testing and isolation strategies, and working from home, as these have important implications for work organisations.

Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns: a systematic review.

BACKGROUND: Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation plays an important role in pathogenesis, antileukotrienes have been explored in both clinical and animal studies. We aimed to assess the benefits and harms of antileukotrienes for the prevention and treatment of respiratory morbidity and mortality in very preterm newborns. METHODS: In this systematic review, we included randomized trials and non-randomized studies in humans and animals reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. Our pre-specified primary outcomes were all-cause mortality and any harm, and, for the clinical studies, incidence of chronic lung disease. Included studies underwent risk of bias-assessment and data extraction performed by two authors independently. There were no language restrictions. RESULTS: Fifteen studies totally met our inclusion criteria: one randomized trial and four non-randomized studies in humans and 10 animal studies (five in rodents, two in lambs and one in either guinea pigs, rabbits or caprinae). All five clinical studies used montelukast and had a small sample size, ranging from 4 to 77 infants. The randomized trial (n = 60) found no difference in the incidence of chronic lung disease between the groups. Only one clinical study, which enrolled four very preterm infants and had a critical overall risk of bias, reported long-term outcomes. All other studies had unclear or greater overall risk of bias and meta-analyses were therefore deemed unfeasible. Eight of ten animal studies used leukotriene receptor antagonists as antileukotriene (montelukast in three of ten studies) and seven had an experimental study design (i.e. some animals were not exposed to antileukotrienes but no randomization). Three of the ten animal studies assessed different doses. Animal studies found no effect on the outcomes mortality, growth, or lung function related surrogate outcomes. CONCLUSIONS: Use of antileukotrienes in very preterm infants to prevent or treat chronic lung disease is not supported by the available evidence. Large randomized trials focusing on outcomes relevant to patients, including long-term outcomes, are needed. Studies should also minimize risk of bias.

Hand cleaning with ash for reducing the spread of viral and bacterial infections: a rapid review.

BACKGROUND: Handwashing is important to reduce the spread and transmission of infectious disease. Ash, the residue from stoves and fires, is a material used for cleaning hands in settings where soap is not widely available. OBJECTIVES: To assess the benefits and harms of hand cleaning with ash compared with hand cleaning using soap or other materials for reducing the spread of viral and bacterial infections. SEARCH METHODS: On 26 March 2020 we searched CENTRAL, MEDLINE, Embase, WHO Global Index Medicus, and the WHO International Clinical Trials Registry Platform. SELECTION CRITERIA: We included all types of studies, in any population, that examined hand cleaning with ash compared to hand cleaning with any other material. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and full texts, and one review author extracted outcome data and assessed risk of bias, which another review author double-checked. We used the ROBINS-I tool for observational studies, we used RoB 2.0 for three interventional studies, and we used GRADE to assess the certainty of the evidence. We planned to synthesise data with random-effects meta-analyses. Our prespecified outcome measures were overall mortality, number of cases of infections (as defined in the individual studies), severity of infectious disease, harms (as reported in the individual studies), and adherence. MAIN RESULTS: We included 14 studies described in 19 records using eight different study designs, but only one randomised trial. The studies were primarily conducted in rural settings in low- and lower-middle-income countries. Six studies reported outcome data relevant to our review. A retrospective case-control study and a cohort study assessed diarrhoea in children under the age of five years and self-reported reproductive tract symptoms in women, respectively. It was very uncertain whether the rate of hospital contacts for moderate-to-severe diarrhoea in children differed between households that cleaned hands using ash compared with households cleaning hands using soap (RR 0.97, 95% CI 0.84 to 1.11; very low-certainty evidence). Similarly, it was very uncertain whether the rate of women experiencing symptoms of reproductive tract infection differed between women cleaning hands with ash compared with cleaning hands using soap (RR 0.48, 95% CI 0.12 to 1.86; very low-certainty evidence) or when compared with handwashing with water only or not washing hands (RR 0.50, 95% CI 0.13 to 1.96; very low-certainty evidence). Four studies reported on bacteriological counts after hand wash. We rated all four studies at high risk of bias, and we did not synthesise data due to methodological heterogeneity and unclear outcome reporting. AUTHORS' CONCLUSIONS: Based on the available evidence, the benefits and harms of hand cleaning with ash compared with soap or other materials for reducing the spread of viral or bacterial infections are uncertain.

Conflicts of interest in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: associations with recommendations.

BACKGROUND: Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest. OBJECTIVES: To investigate to what degree financial and non-financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. SEARCH METHODS: We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources. SELECTION CRITERIA: We included studies comparing the association between conflicts of interest and favourable recommendations of drugs or devices (e.g. recommending a particular drug) in clinical guidelines, advisory committee reports, opinion pieces, or narrative reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently included studies, extracted data, and assessed risk of bias. When a meta-analysis was considered meaningful to synthesise our findings, we used random-effects models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), with RR > 1 indicating that documents (e.g. clinical guidelines) with conflicts of interest more often had favourable recommendations. We analysed associations for financial and non-financial conflicts of interest separately, and analysed the four types of documents both separately (pre-planned analyses) and combined (post hoc analysis). MAIN RESULTS: We included 21 studies analysing 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews. We received unpublished data from 11 studies; eight full data sets and three summary data sets. Fifteen studies had a risk of confounding, as they compared documents that may differ in other aspects than conflicts of interest (e.g. documents on different drugs used for different populations). The associations between financial conflicts of interest and favourable recommendations were: clinical guidelines, RR: 1.26, 95% CI: 0.93 to 1.69 (four studies of 86 clinical guidelines); advisory committee reports, RR: 1.20, 95% CI: 0.99 to 1.45 (four studies of 629 advisory committee reports); opinion pieces, RR: 2.62, 95% CI: 0.91 to 7.55 (four studies of 284 opinion pieces); and narrative reviews, RR: 1.20, 95% CI: 0.97 to 1.49 (four studies of 457 narrative reviews). An analysis combining all four document types supported these findings (RR: 1.26, 95% CI: 1.09 to 1.44). One study investigating specialty interests found that the association between including radiologist guideline authors and recommending routine breast cancer screening was RR: 2.10, 95% CI: 0.92 to 4.77 (12 clinical guidelines). AUTHORS' CONCLUSIONS: We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.

Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study.

BACKGROUND: Large reductions in the incidence of abdominal aortic aneurysm (AAA) and AAA-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of AAA screening in Sweden on disease-specific mortality, incidence, and surgery. METHODS: Individual data on the incidence of AAA, AAA mortality, and surgery for AAA in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for AAA screening. We also analysed national data for all men aged 40-99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. FINDINGS: AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65-74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio [aOR] 0·76, 95% CI 0·38-1·51), which means that two men (95% CI -3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16-1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20-2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25-73) were likely to be overdiagnosed, 19 of whom (95% CI 1-37) had avoidable surgery that increased their risk of mortality and morbidity. INTERPRETATION: AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question. FUNDING: Research Unit and Section for General Practice, FoUU-centrum Fyrbodal, Sweden, and the region of Västra Götaland, Sweden.

General health checks in adults for reducing morbidity and mortality from disease.

BACKGROUND: General health checks are common elements of health care in some countries. They aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used individual screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is therefore important to assess whether general health checks do more good than harm. This is the first update of the review published in 2012. OBJECTIVES: To quantify the benefits and harms of general health checks. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases and two trials registers on 31 January 2018. Two review authors independently screened titles and abstracts, assessed papers for eligibility and read reference lists. One review author used citation tracking (Web of Knowledge) and asked trial authors about additional studies. SELECTION CRITERIA: We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening for more than one disease or risk factor in more than one organ system. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the trials. We contacted trial authors for additional outcomes or trial details when necessary. When possible, we analysed the results with a random-effects model meta-analysis; otherwise, we did a narrative synthesis. MAIN RESULTS: We included 17 trials, 15 of which reported outcome data (251,891 participants). Risk of bias was generally low for our primary outcomes. Health checks have little or no effect on total mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.97 to 1.03; 11 trials; 233,298 participants and 21,535 deaths; high-certainty evidence, I2 = 0%), or cancer mortality (RR 1.01, 95% CI 0.92 to 1.12; 8 trials; 139,290 participants and 3663 deaths; high-certainty evidence, I2 = 33%), and probably have little or no effect on cardiovascular mortality (RR 1.05, 95% CI 0.94 to 1.16; 9 trials; 170,227 participants and 6237 deaths; moderate-certainty evidence; I2 = 65%). Health checks have little or no effect on fatal and non-fatal ischaemic heart disease (RR 0.98, 95% CI 0.94 to 1.03; 4 trials; 164,881 persons, 10,325 events; high-certainty evidence; I2 = 11%), and probably have little or no effect on fatal and non-fatal stroke (RR 1.05 95% CI 0.95 to 1.17; 3 trials; 107,421 persons, 4543 events; moderate-certainty evidence, I2 = 53%). AUTHORS' CONCLUSIONS: General health checks are unlikely to be beneficial.

Screening for reducing morbidity and mortality in malignant melanoma.

BACKGROUND: Screening for malignant melanoma has the potential to reduce morbidity and mortality from the disease through earlier detection, as prognosis is closely associated with the thickness of the lesion at the time of diagnosis. However, there are also potential harms from screening people without skin lesion concerns, such as overdiagnosis of lesions that would never have caused symptoms if they had remained undetected. Overdiagnosis results in harm through unnecessary treatment and the psychosocial consequences of being labelled with a cancer diagnosis. For any type of screening, the benefits must outweigh the harms. Screening for malignant melanoma is currently practised in many countries, and the incidence of the disease is rising sharply, while mortality remains largely unchanged. OBJECTIVES: To assess the effects on morbidity and mortality of screening for malignant melanoma in the general population. SEARCH METHODS: We searched the following databases up to May 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registries, checked the reference lists of included and other relevant studies for further references to randomised controlled trials (RCTs), used citation tracking (Web of Science) for key articles, and asked trialists about additional studies and study reports. SELECTION CRITERIA: RCTs, including cluster-randomised trials, of screening for malignant melanoma compared with no screening, regardless of screening modality or setting, in any type of population and in any age group where people were not suspected of having malignant melanoma. We excluded studies in people with a genetic disposition for malignant melanoma (e.g. familial atypical mole and melanoma syndrome) and studies performed exclusively in people with previous melanomas. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes of this review were total mortality, overdiagnosis of malignant melanoma, and quality of life/psychosocial consequences. MAIN RESULTS: We included two studies with 64,391 participants. The first study was a randomised trial of an intervention developed to increase the rate of performance of thorough skin self-examination. The intervention group received instructional materials, including cues and aids, a 14-minute instruction video, and a brief counselling session, and at three weeks a brief follow-up telephone call from a health educator, aimed at increasing performance of thorough skin self-examination. The control group received a diet intervention with similar follow-up. The trial included 1356 people, who were recruited from 11 primary care practices in the US between 2000 and 2001. Participant mean age was 53.2 years and 41.7% were men. This study did not report on any of our primary outcomes or the following secondary outcomes: mortality specific to malignant melanoma, false-positive rates (skin biopsies/excisions with benign outcome), or false-negative rates (malignant melanomas diagnosed between screening rounds and up to one year after the last round). All participants were asked to complete follow-up telephone interviews at 2, 6, and 12 months after randomisation.The second study was a pilot study for a cluster-RCT of population-based screening for malignant melanoma in Australia. This pilot trial included 63,035 adults aged over 30 years. The three-year programme involved community education, an education and support component for medical practitioners, and the provision of free skin screening services. The mean age of people attending the skin screening clinics (which were held by primary care physicians in workplaces, community venues, and local hospitals, and included day and evening sessions) was 46.5 years, and 51.5% were men. The study included whole communities, targeting participants over 30 years of age, but information on age and gender of the whole study population was not reported. Study duration was three years (1998 to 2001), and outcomes were measured at the screening clinics during these three years. There was no further follow-up for any outcomes. The control group received no programme. The ensuing, planned cluster randomised trial in 560,000 adults was never carried out due to lack of funding. At the time of this review, there are no published or unpublished data on our prespecified outcomes available, and no results for mortality outcomes from the pilot study are to be expected.The risk of bias in these studies was high for performance bias (blinding study personnel and participants) and high or unclear for detection bias (blinding of outcome assessment). Risk of bias in the other domains was either unclear or low. We were unable to assess the certainty of the evidence for our primary outcomes as planned due to lack of data. AUTHORS' CONCLUSIONS: Adult general population screening for malignant melanoma is not supported or refuted by current evidence from RCTs. It therefore does not fulfil accepted criteria for implementation of population screening programmes. This review did not investigate the effects of screening people with a history of malignant melanoma or in people with a genetic disposition for malignant melanoma (e.g. familial atypical mole and melanoma syndrome). To determine the benefits and harms of screening for malignant melanoma, a rigorously conducted randomised trial is needed, which assesses overall mortality, overdiagnosis, psychosocial consequences, and resource use.

Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis.

BACKGROUND: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. OBJECTIVE: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). DESIGN: Cohort study. SETTING: Denmark from 1980 to 2010. PARTICIPANTS: Women aged 35 to 84 years. INTERVENTION: Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times. MEASUREMENTS: Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas. RESULTS: Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]). LIMITATION: Regional differences complicate interpretation. CONCLUSION: Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%). PRIMARY FUNDING SOURCE: None.

National clinical guidelines for non-surgical treatment of patients with recent onset neck pain or cervical radiculopathy.

PURPOSE: To summarise recommendations about 21 selected non-surgical interventions for recent onset (<12 weeks) non-specific neck pain (NP) and cervical radiculopathy (CR) based on two guidelines from the Danish Health Authority. METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach. RESULTS: Twelve recommendations were based on evidence and nine on consensus. Management should include information about prognosis, warning signs, and advise to remain active. For treatment, guidelines suggest different types of supervised exercise and manual therapy; combinations of exercise and manual therapy before medicine for NP; acupuncture for NP but not CR; traction for CR; and oral NSAID (oral or topical) and Tramadol after careful consideration for NP and CR. CONCLUSION: Recommendations are based on low-quality evidence or on consensus, but are well aligned with recommendations from guidelines from North America. The working groups recommend intensifying research relating to all aspects of management of NP and CR.

The Cochrane Collaboration withdraws a review on methylphenidate for adults with attention deficit hyperactivity disorder.

A Cochrane systematic review on immediate-release methylphenidate for adults with attention deficit hyperactivity disorder (ADHD) was withdrawn from the Cochrane Library on 26 May 2016 after substantial criticism of its methods and flawed conclusions. Retraction of scientific papers on this basis is unusual but can be necessary. We provide a summary of the criticism that led to the withdrawal. We detail the methodological flaws of the withdrawn Cochrane systematic review and general issues of bias and shortcomings of the included ADHD trials: cross-over designs compared with parallel-group designs, exclusion of participants with psychiatric comorbidity, absence of 'functional outcomes' and use of clinical outcomes with limited relevance, short trial duration and small trial populations, broken blinding caused by easily recognisable side effects, combining outcome assessments by trial investigators and participants, outcome reporting bias, poor evaluation of cardiovascular and psychiatric harms and conflicts of interest of trialists and systematic reviewers. The withdrawal of the Cochrane systematic review signals recognition of previous unreliable clinical ADHD research. We conclude that clinical trials of immediate-release methylphenidate in adults with ADHD are of very low quality. We urgently need well-conducted long-term trials free of bias to assess the benefits and harms of central stimulant treatment in adult ADHD.

Treatment for women with postpartum iron deficiency anaemia.

BACKGROUND: Postpartum iron deficiency anaemia is caused by bleeding or inadequate dietary iron intake/uptake. This condition is defined by iron deficiency accompanied by a lower than normal blood haemoglobin concentration, although this can be affected by factors other than anaemia and must be interpreted in the light of any concurrent symptoms. Symptoms include fatigue, breathlessness, and dizziness. Treatment options include oral or intravenous iron, erythropoietin which stimulates red blood cell production, and substitution by red blood cell transfusion. OBJECTIVES: To assess the efficacy and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. SEARCH METHODS: The Cochrane Pregnancy and Childbirth Group's Trials Register (9 April 2015); the WHO International Clinical Trials Registry Portal (ICTRP), and the Latin-American and Caribbean Health Sciences Literature database (LILACS) (8 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished and ongoing randomised controlled trials that compared a treatment for postpartum iron deficiency anaemia with placebo, no treatment, or another treatment for postpartum iron deficiency anaemia, including trials described in abstracts only. Cluster-randomised trials were eligible for inclusion. We included both open-label trials and blinded trials, regardless of who was blinded. The participants were women with a postpartum haemoglobin of 120 g per litre (g/L) or less, for which treatment was initiated within six weeks after childbirth.Non-randomised trials, quasi-randomised trials and trials using a cross-over design were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, quality, and extracted data. We contacted study authors and pharmaceutical companies for additional information. MAIN RESULTS: We included 22 randomised controlled trials (2858 women), most of which had high risk of bias in several domains. We performed 13 comparisons. Many comparisons are based on a small number of studies with small sample sizes. No analysis of our primary outcomes contained more than two studies.Intravenous iron was compared to oral iron in 10 studies (1553 women). Fatigue was reported in two studies and improved significantly favouring the intravenously treated group in one of the studies. Other anaemia symptoms were not reported. One woman died from cardiomyopathy (risk ratio (RR) 2.95; 95% confidence interval (CI) 0.12 to 71.96; two studies; one event; 374 women; low quality evidence). One woman developed arrhythmia. Both cardiac complications occurred in the intravenously treated group. Allergic reactions occurred in three women treated with intravenous iron, not statistically significant (average RR 2.78; 95% CI 0.31 to 24.92; eight studies; 1454 women; I² = 0%; low quality evidence). Gastrointestinal events were less frequent in the intravenously treated group (average RR 0.31; 95% CI 0.20 to 0.47; eight studies; 169 events; 1307 women; I² = 0%; very low quality evidence).One study evaluated red blood cell transfusion versus non-intervention. General fatigue improved significantly more in the transfusion group at three days (MD -0.80; 95% CI -1.53 to -0.07; women 388; low quality evidence), but no difference between groups was seen at six weeks. Maternal mortality was not reported.The remaining comparisons evaluated oral iron (with or without other food substances) versus placebo (three studies), intravenous iron with oral iron versus oral iron (two studies) and erythropoietin (alone or combined with iron) versus placebo or iron (seven studies). These studies did not investigate fatigue. Maternal mortality was rarely reported. AUTHORS' CONCLUSIONS: The body of evidence did not allow us to reach a clear conclusion regarding the efficacy of the interventions on postpartum iron deficiency anaemia. The quality of evidence was low.Clinical outcomes were rarely reported. Laboratory values may not be reliable indicators for efficacy, as they do not always correlate with clinical treatment effects. It remains unclear which treatment modality is most effective in alleviating symptoms of postpartum anaemia.Intravenous iron was superior regarding gastrointestinal harms, however anaphylaxis and cardiac events occurred and more data are needed to establish whether this was caused by intravenous iron.The clinical significance of some temporarily improved fatigue scores in women treated with blood transfusion is uncertain and this modest effect should be balanced against known risks, e.g. maternal mortality (not reported) and maternal immunological sensitisation, which can potentially harm future pregnancies.When comparing oral iron to placebo it remains unknown whether efficacy (relief of anaemia symptoms) outweighs the documented gastrointestinal harms.We could not draw conclusions regarding erythropoietin treatment due to lack of evidence.Further research should evaluate treatment effect through clinical outcomes, i.e. presence and severity of anaemia symptoms balanced against harms, i.e. survival and severe morbidity.

Screening with urinary dipsticks for reducing morbidity and mortality.

BACKGROUND: Urinary dipsticks are sometimes used for screening asymptomatic people, and for case-finding among inpatients or outpatients who do not have genitourinary symptoms. Abnormalities identified on screening sometimes lead to additional investigations, which may identify serious disease, such as bladder cancer and chronic kidney disease (CKD). Urinary dipstick screening could improve prognoses due to earlier detection, but could also lead to unnecessary and potentially invasive follow-up testing and unnecessary treatment. OBJECTIVES: We aimed to quantify the benefits and harms of screening with urinary dipsticks in general populations and patients in hospitals. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 8 September 2014 through contact with the Trials Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials and other study types that compared urinary dipstick screening with no dipstick screening were eligible for inclusion. We searched for studies that investigated the use of urinary dipsticks for detecting haemoglobin, protein, albumin, albumin-creatinine ratio, leukocytes, nitrite, or glucose, alone or in any combination, and in any setting. We planned to exclude studies conducted in patients with urinary disorders. DATA COLLECTION AND ANALYSIS: It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. However, no studies met our inclusion criteria. MAIN RESULTS: Literature searches to 8 September 2014 yielded 4298 records, of which 4249 were excluded following title and abstract assessment. There were 49 records (44 studies) eligible for full text assessment; of these 18 studies were not RCTs and 26 studies compared interventions or controls that were not relevant to this review. Thus, no studies were eligible for inclusion. AUTHORS' CONCLUSIONS: We found no evidence to assess the benefits and harms of screening with urinary dipsticks, which remain unknown.