Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL, and two trials registers in October 2022, with backwards and forwards citation analysis on the new studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, glasses, and gargling) to prevent respiratory virus transmission.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 11 new RCTs and cluster-RCTs (610,872 participants) in this update, bringing the total number of RCTs to 78. Six of the new trials were conducted during the COVID-19 pandemic; two from Mexico, and one each from Denmark, Bangladesh, England, and Norway. We identified four ongoing studies, of which one is completed, but unreported, evaluating masks concurrent with the COVID-19 pandemic. Many studies were conducted during non-epidemic influenza periods. Several were conducted during the 2009 H1N1 influenza pandemic, and others in epidemic influenza seasons up to 2016. Therefore, many studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Adherence with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included 12 trials (10 cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza-like illness (ILI)/COVID-19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate-certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory-confirmed influenza/SARS-CoV-2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate-certainty evidence). Harms were rarely measured and poorly reported (very low-certainty evidence). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). We are very uncertain on the effects of N95/P2 respirators compared with medical/surgical masks on the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 3 trials, 7779 participants; very low-certainty evidence). N95/P2 respirators compared with medical/surgical masks may be effective for ILI (RR 0.82, 95% CI 0.66 to 1.03; 5 trials, 8407 participants; low-certainty evidence). Evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirators compared to medical/surgical masks probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 5 trials, 8407 participants; moderate-certainty evidence). Restricting pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies (very low-certainty evidence).  One previously reported ongoing RCT has now been published and observed that medical/surgical masks were non-inferior to N95 respirators in a large study of 1009 healthcare workers in four countries providing direct care to COVID-19 patients.  Hand hygiene compared to control Nineteen trials compared hand hygiene interventions with controls with sufficient data to include in meta-analyses. Settings included schools, childcare centres and homes. Comparing hand hygiene interventions with controls (i.e. no intervention), there was a 14% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.86, 95% CI 0.81 to 0.90; 9 trials, 52,105 participants; moderate-certainty evidence), suggesting a probable benefit. In absolute terms this benefit would result in a reduction from 380 events per 1000 people to 327 per 1000 people (95% CI 308 to 342). When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.94, 95% CI 0.81 to 1.09; 11 trials, 34,503 participants; low-certainty evidence), and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials, 8332 participants; low-certainty evidence), suggest the intervention made little or no difference. We pooled 19 trials (71, 210 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. Pooled data showed that hand hygiene may be beneficial with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.83 to 0.94; low-certainty evidence), but with high heterogeneity. In absolute terms this benefit would result in a reduction from 200 events per 1000 people to 178 per 1000 people (95% CI 166 to 188). Few trials measured and reported harms (very low-certainty evidence). We found no RCTs on gowns and gloves, face shields, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory-confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old. METHODS: ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to <12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28-56 days after the additional dose of Rotarix or placebo. RESULTS: Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events. CONCLUSIONS: An additional dose of Rotarix administered to Australian Aboriginal infants 6 to <12 months old increased the proportion with a vaccine seroresponse. CLINICAL TRIALS REGISTRATION: NCT02941107.

SARS-CoV-2 infection in heart transplant recipients: a systematic literature review of clinical outcomes and immunosuppression strategies.

The impact of SARS-CoV-2 infection on heart transplant recipients is unknown. Literature is limited to case reports and series. The purpose of this study is to identify the clinical features, outcomes, and immunosuppression strategies of heart transplant recipients with COVID-19 infection. A systematic review was conducted using the search term "Coronavirus" or COVID," "SARS-CoV-2," "cardiac transplantation," and "heart transplant." Case reports and retrospective studies were gathered by searching Medline/PubMed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science. Thirty-three articles were selected for review. We identified 74 cases of SARS-CoV-2 infection in heart transplant and heart-kidney transplant recipients. The mean age was 60.5 ± 15.8 years, and 82.4% were males with median time from transplant of 6.5 years. Commonest symptoms were fever, cough, and dyspnea, but new left ventricular (LV) dysfunction was rare. Leukocytosis, lymphopenia, elevated inflammatory markers, and bilateral ground-glass opacities were common. Mortality was high, with particularly poor survival in patients who required intensive care unit (ICU) admission and older patients. Immunosuppression involved discontinuation of antimetabolites and steroids. COVID-19 infection in heart transplant (HT) recipients presents similarly to the general population, but new onset of LV dysfunction is uncommon. Immunosuppression strategies include increase in corticosteroids and discontinuation of antimetabolites.

Impact of Rotavirus Vaccines on Gastroenteritis Hospitalizations in Western Australia: A Time-series Analysis.

BACKGROUND: Rotavirus vaccination was introduced into the Australian National Immunisation Program in mid-2007. We aimed to assess the impact of the rotavirus vaccination program on the burden of hospitalizations associated with all-cause acute gastroenteritis (including rotavirus gastroenteritis and non-rotavirus gastroenteritis) in the Aboriginal and non-Aboriginal population in Western Australia. METHODS: We identified all hospital records, between July 2004 and June 2012, with a discharge diagnosis code for all-cause gastroenteritis. Age-specific hospitalization rates for rotavirus and non-rotavirus acute gastroenteritis before and after the introduction of the rotavirus vaccination program were compared. Interrupted time-series models were used to examine differences in the annual trends of all-cause gastroenteritis hospitalization between the two periods. RESULTS: Between July 2004 and June 2012, there were a total of 106,974 all-cause gastroenteritis-coded hospitalizations (1,381 rotavirus-coded [15% among Aboriginal] and 105,593 non-rotavirus gastroenteritis-coded [7% among Aboriginal]). Following rotavirus vaccination introduction, significant reductions in rotavirus-coded hospitalization rates were observed in all children aged <5 years (up to 79% among non-Aboriginal and up to 66% among Aboriginal). Among adults aged ≥65 years, rotavirus-coded hospitalizations were 89% (95% confidence interval, 16-187%) higher in the rotavirus vaccination program period. The time-series analysis suggested reductions in all-cause gastroenteritis hospitalizations in the post-vaccination period among both vaccinated and unvaccinated (age-ineligible) children, with increases observed in adults aged ≥45 years. CONCLUSIONS: Rotavirus vaccination has been associated with a significant decline in gastroenteritis hospitalizations among children. The increase in the elderly requires further evaluation, including assessment of the cost-benefits of rotavirus vaccination in this population.

Left Ventricular Impaired Relaxation and Interstitial Myocarditis Identified in Sepsis-Associated Cardiac Dysfunction: Use of a Rodent Model.

BACKGROUND Sepsis is a serious clinical problem that results from the systemic response of the body to infection. Left ventricular (LV) diastolic dysfunction is increasingly appreciated as a contributor to morbidity and mortality in sepsis. Animal models may offer a method of studying diastolic dysfunction while controlling for many potential clinical confounders, such as sepsis duration, premorbid condition, and therapeutic interventions. This study sought to evaluate an endotoxemia (LPS) rodent model of sepsis, with regard to echocardiographic evidence, including tissue Doppler, of LV diastolic dysfunction and histopathology findings. MATERIAL AND METHODS Fourteen male Sprague-Dawley rats were randomly allocated (1: 1) to LPS or saline (control). Mean arterial blood pressure (MAP) was measured through cannulation of the carotid artery. After a 30-min stabilization, baseline assessment with echocardiography and blood collection was performed. Rats were administered 0.9% saline or LPS (10 mg/mL). Follow-up echocardiography and blood collection were performed after 2 h. Hearts were removed post-mortem and pathology studied using histology and immunohistochemistry. RESULTS LPS was associated with hypotension (MAP 81.86±31.67 mmHg; 124.29±20.16; p=0.02) and LV impaired relaxation (myocardial early diastolic velocity [e'] 0.06±0.02 m/s; 0.09±0.02; P=0.008). Histopathology and immunohistochemistry demonstrated evidence of interstitial myocarditis (hydropic changes and inflammation). CONCLUSIONS LPS was associated with both diastolic dysfunction (impaired relaxation) and interstitial myocarditis. These features may offer a link between the structural and functional changes that have previously been described separately in clinical sepsis. This may facilitate further studies focused upon the mechanism and potential benefit treatment of sepsis-associated cardiac dysfunction.

Short- and Long-Term Effects of a Scapular-Focused Exercise Protocol for Patients with Shoulder Dysfunctions-A Prospective Cohort.

Current clinical practice lacks consistent evidence in the management of scapular dyskinesis. This study aims to determine the short- and long-term effects of a scapular-focused exercise protocol facilitated by real-time electromyographic biofeedback (EMGBF) on pain and function, in individuals with rotator cuff related pain syndrome (RCS) and anterior shoulder instability (ASI). One-hundred and eighty-three patients were divided into two groups (n = 117 RCS and n = 66 ASI) and guided through a structured exercise protocol, focusing on scapular dynamic control. Values of pain and function (shoulder pain and disability index (SPADI) questionnaire, complemented by the numeric pain rating scale (NPRS) and disabilities of the arm, shoulder, and hand (DASH) questionnaire) were assessed at the initial, 4-week, and 2-year follow-up and compared within and between. There were significant differences in pain and function improvement between the initial and 4-week assessments. There were no differences in the values of DASH 1st part and SPADI between the 4-week and 2-year follow-up. There were no differences between groups at the baseline and long-term, except for DASH 1st part and SPADI (p < 0.05). Only 29 patients (15.8%) had a recurrence episode at follow-up. These results provide valuable information on the positive results of the protocol in the short- and long-term.

Estimating the magnitude of cancer overdiagnosis in Australia.

OBJECTIVES: To estimate the proportion of cancer diagnoses in Australia that might reasonably be attributed to overdiagnosis by comparing current and past lifetime risks of cancer. DESIGN, SETTING, AND PARTICIPANTS: Routinely collected Australian Institute of Health and Welfare national data were analysed to estimate recent (2012) and historical (1982) lifetime risks (adjusted for competing risk of death and changes in risk factors) of diagnoses with five cancers: prostate, breast, renal, thyroid cancers, and melanoma. MAIN OUTCOME MEASURE: Difference in lifetime risks of cancer diagnosis between 1982 and 2012, interpreted as probable overdiagnosis. RESULTS: For women, absolute lifetime risk increased by 3.4 percentage points for breast cancer (invasive cancers, 1.7 percentage points), 0.6 percentage point for renal cancer, 1.0 percentage point for thyroid cancer, and 5.1 percentage points for melanoma (invasive melanoma, 0.7 percentage point). An estimated 22% of breast cancers (invasive cancers, 13%), 58% of renal cancers, 73% of thyroid cancers, and 54% of melanomas (invasive melanoma, 15%) were overdiagnosed, or 18% of all cancer diagnoses (8% of invasive cancer diagnoses). For men, absolute lifetime risk increased by 8.2 percentage points for prostate cancer, 0.8 percentage point for renal cancer, 0.4 percentage point for thyroid cancer, and 8.0 percentage points for melanoma (invasive melanoma, 1.5 percentage points). An estimated 42% of prostate cancers, 42% of renal cancers, 73% of thyroid cancers, and 58% of melanomas (invasive melanomas, 22%) were overdiagnosed, or 24% of all cancer diagnoses (16% of invasive cancer diagnoses). Alternative assumptions slightly modified the estimates for overdiagnosis of breast cancer and melanoma. CONCLUSIONS: About 11 000 cancers in women and 18 000 in men may be overdiagnosed each year. Rates of overdiagnosis need to be reduced and health services should monitor emerging areas of overdiagnosis.

Is the risk of cancer in Australia overstated? The importance of competing mortality for estimating lifetime risk.

OBJECTIVES: To calculate lifetime risks of cancer diagnosis and cancer-specific death, adjusted for competing mortality, and to compare these estimates with the corresponding risks published by the Australian Institute of Health and Welfare (AIHW). DESIGN, SETTING: Analysis of publicly available annual AIHW data on age-specific cancer incidence and mortality - for breast cancer, colorectal cancer, prostate cancer, melanoma of the skin, and lung cancer - and all-cause mortality in Australia, 1982-2013. OUTCOME MEASURES: Lifetime risks of cancer diagnosis and mortality (to age 85), adjusted for competing mortality. RESULTS: During 1982-2013, AIHW estimates were consistently higher than our competing mortality-adjusted estimates of lifetime risks of diagnosis and death for all five cancers. Differences between AIHW and adjusted estimates declined with time for breast cancer, prostate cancer, colorectal cancer, and lung cancer (for men only), but remained steady for lung cancer (women only) and melanoma of the skin. In 2013, the respective estimated lifetime risks of diagnosis (AIHW and adjusted) were 12.7% and 12.1% for breast cancer, 18.7% and 16.2% for prostate cancer, 9.0% and 7.0% (men) and 6.4% and 5.5% (women) for colorectal cancer, 7.5% and 6.0% (men) and 4.4% and 4.0% (women) for melanoma of the skin, and 7.6% and 5.8% (men) and 4.5% and 3.9% (women) for lung cancer. CONCLUSION: The method employed in Australia to calculate the lifetime risks of cancer diagnosis and mortality overestimates these risks, especially for men.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review published in 2007, 2009, 2010, and 2011. The evidence summarised in this review does not include results from studies from the current COVID-19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL on 1 April 2020. We searched ClinicalTrials.gov, and the WHO ICTRP on 16 March 2020. We conducted a backwards and forwards citation analysis on the newly included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs of trials investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, and gargling) to prevent respiratory virus transmission. In previous versions of this review we also included observational studies. However, for this update, there were sufficient RCTs to address our study aims.   DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Three pairs of review authors independently extracted data using a standard template applied in previous versions of this review, but which was revised to reflect our focus on RCTs and cluster-RCTs for this update. We did not contact trialists for missing data due to the urgency in completing the review. We extracted data on adverse events (harms) associated with the interventions. MAIN RESULTS: We included 44 new RCTs and cluster-RCTs in this update, bringing the total number of randomised trials to 67. There were no included studies conducted during the COVID-19 pandemic. Six ongoing studies were identified, of which three evaluating masks are being conducted concurrent with the COVID pandemic, and one is completed. Many studies were conducted during non-epidemic influenza periods, but several studies were conducted during the global H1N1 influenza pandemic in 2009, and others in epidemic influenza seasons up to 2016. Thus, studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID-19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high-income countries; crowded inner city settings in low-income countries; and an immigrant neighbourhood in a high-income country. Compliance with interventions was low in many studies. The risk of bias for the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included nine trials (of which eight were cluster-RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and seven in the community). There is low certainty evidence from nine trials (3507 participants) that wearing a mask may make little or no difference to the outcome of influenza-like illness (ILI) compared to not wearing a mask (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.82 to 1.18. There is moderate certainty evidence that wearing a mask probably makes little or no difference to the outcome of laboratory-confirmed influenza compared to not wearing a mask (RR 0.91, 95% CI 0.66 to 1.26; 6 trials; 3005 participants). Harms were rarely measured and poorly reported. Two studies during COVID-19 plan to recruit a total of 72,000 people. One evaluates medical/surgical masks (N = 6000) (published Annals of Internal Medicine, 18 Nov 2020), and one evaluates cloth masks (N = 66,000). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). There is uncertainty over the effects of N95/P2 respirators when compared with medical/surgical masks on the outcomes of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; very low-certainty evidence; 3 trials; 7779 participants) and ILI (RR 0.82, 95% CI 0.66 to 1.03; low-certainty evidence; 5 trials; 8407 participants). The evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirator compared to a medical/surgical mask probably makes little or no difference for the objective and more precise outcome of laboratory-confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; moderate-certainty evidence; 5 trials; 8407 participants). Restricting the pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies. One ongoing study recruiting 576 people compares N95/P2 respirators with medical surgical masks for healthcare workers during COVID-19. Hand hygiene compared to control Settings included schools, childcare centres, homes, and offices. In a comparison of hand hygiene interventions with control (no intervention), there was a 16% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.84, 95% CI 0.82 to 0.86; 7 trials; 44,129 participants; moderate-certainty evidence), suggesting a probable benefit. When considering the more strictly defined outcomes of ILI and laboratory-confirmed influenza, the estimates of effect for ILI (RR 0.98, 95% CI 0.85 to 1.13; 10 trials; 32,641 participants; low-certainty evidence) and laboratory-confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials; 8332 participants; low-certainty evidence) suggest the intervention made little or no difference. We pooled all 16 trials (61,372 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. The pooled data showed that hand hygiene may offer a benefit with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.84 to 0.95; low-certainty evidence), but with high heterogeneity. Few trials measured and reported harms. There are two ongoing studies of handwashing interventions in 395 children outside of COVID-19. We identified one RCT on quarantine/physical distancing. Company employees in Japan were asked to stay at home if household members had ILI symptoms. Overall fewer people in the intervention group contracted influenza compared with workers in the control group (2.75% versus 3.18%; hazard ratio 0.80, 95% CI 0.66 to 0.97). However, those who stayed at home with their infected family members were 2.17 times more likely to be infected. We found no RCTs on eye protection, gowns and gloves, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low compliance with the interventions during the studies hamper drawing firm conclusions and generalising the findings to the current COVID-19 pandemic. There is uncertainty about the effects of face masks. The low-moderate certainty of the evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of randomised trials did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks during seasonal influenza. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness. Harms associated with physical interventions were under-investigated. There is a need for large, well-designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, especially in those most at risk of ARIs.

A Multicenter Collaboration to Assess the Safety of Laparoscopic Ventral Rectopexy.

BACKGROUND: Concerns have been raised regarding the potential risk of mesh complications after laparoscopic ventral rectopexy. OBJECTIVE: This study aimed to determine the risk of mesh and nonmesh morbidity after laparoscopic ventral rectopexy and to compare the safety of synthetic meshes with biological grafts. DESIGN: This was a retrospective review. SETTINGS: The study used data collated from prospective pelvic floor databases in 5 centers (3 in the United Kingdom, 1 in Australia, and 1 in Italy). PATIENTS: All of the patients undergoing laparoscopic ventral rectopexy over a 14-year period (1999-2013) at these centers were included in the study. MAIN OUTCOME MEASURES: The primary outcome was mesh morbidity, classified as vaginal erosion, rectal erosion, rectovaginal fistula, or perineal erosion. Secondary outcomes were nonmesh morbidity. RESULTS: A total of 2203 patients underwent surgery; 1764 (80.1%) used synthetic mesh and 439 (19.9%) used biological grafts. There were 2 postoperative deaths (0.1%). Forty-five patients (2.0%) had mesh erosion, including 20 vaginal, 17 rectal, 7 rectovaginal fistula, and 1 perineal. Twenty-three patients (51.1%) required treatment for minor erosion morbidity (local excision of stitch/exposed mesh), and 18 patients (40.0%) were treated for major erosion morbidity (12 laparoscopic mesh removal, 3 mesh removal plus colostomy, and 3 anterior resection). Erosion occurred in 2.4% of synthetic meshes and 0.7% of biological meshes. The median time to erosion was 23 months. Nonmesh complications occurred in 11.1% of patients. LIMITATIONS: This was a retrospective study including patients with minimal follow-up. The study was unable to determine whether patients will develop future erosions, currently have asymptomatic erosions, or have been treated in other institutions for erosions. CONCLUSIONS: Laparoscopic ventral rectopexy is a safe operation. Mesh erosion rates are 2% and occasionally require resectional surgery that might be reduced by the use of biological graft. An international ventral mesh registry is recommended to monitor mesh problems and to assess whether type of mesh has any impact on functional outcomes or the need for revisional surgery for nonerosion problems.

Post-exposure passive immunisation for preventing measles.

BACKGROUND: Measles outbreaks continue to occur in countries with high vaccination coverage. Passive immunisation is generally considered to prevent measles in someone who is not immune and has been exposed to infection. Estimates of effectiveness have varied and no minimum effective dose has been determined. OBJECTIVES: To assess the effectiveness and safety of intramuscular injection or intravenous infusion of immunoglobulins (passive immunisation) for preventing measles when administered to exposed susceptible people before the onset of symptoms. SEARCH METHODS: We searched CENTRAL (2013, Issue 7), MEDLINE (1946 to July week 5, 2013), CINAHL (1981 to August 2013) and EMBASE (1974 to August 2013). SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and prospective, controlled (cohort) studies if: participants were susceptible and exposed to measles, polyclonal immunoglobulins derived from human sera or plasma were administered intramuscularly or intravenously as the only intervention in at least one group and the number of subsequent measles cases was measured. We excluded studies of other sources of immunoglobulins. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and critically appraised the included studies. We attempted to contact study authors for missing information. We described the results of studies not included in meta-analyses. MAIN RESULTS: We included one RCT, two quasi-RCTs and 10 cohort studies (3925 participants). No studies were rated as low risk of bias for all criteria. Critical appraisal was constrained by a lack of information in most studies. The overall quality of the evidence was moderate.Seven studies (1432 participants) assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity was explained by subgrouping according to the blood product used as an approximation of dose of immunoglobulin. When given within seven days of exposure, immunoglobulins were effective at preventing measles: gamma globulin (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of different blood products were supported by studies not included in the meta-analysis and by two studies (702 participants) that found gamma globulin more effective than serum (RR 0.56, 95% CI 0.46 to 0.69).Based on three studies (893 participants) immunoglobulin was effective at preventing death due to measles compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44).Two studies included measles vaccine alone among the intervention groups. Meta-analysis could not be undertaken. Both studies suggested the vaccine was more effective than gamma globulin.No serious adverse events were observed in any of the included studies, although reporting of adverse events was poor overall. Non-serious adverse events included transient fever, rash, muscle stiffness, local redness and induration. AUTHORS' CONCLUSIONS: Passive immunisation within seven days of exposure is effective at preventing measles, with the risk for non-immune people up to 83% less than if no treatment is given. Given an attack rate of 45 per 1000 (per the control group of the most recent included study), gamma globulin compared to no treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the attack rate of the other included study assessing gamma globulin), the ARR of gamma globulin compared to no treatment is 629 and the NNTB is two.It seems the dose of immunoglobulin administered impacts on effectiveness. A minimum effective dose of measles-specific antibodies could not be identified.Passive immunisation is effective at preventing deaths from measles, reducing the risk by 76% compared to no treatment. Whether the benefits of passive immunisation vary among subgroups of non-immune exposed people could not be determined.Due to a paucity of evidence comparing vaccine to passive immunisation, no firm conclusions can be drawn regarding relative effectiveness.The included studies were not specifically designed to detect adverse events.Future research should consider the effectiveness of passive immunisation for preventing measles in high-risk populations such as pregnant women, immunocompromised people and infants. Further efforts should be made to determine the minimum effective dose of measles-specific antibodies for post-exposure prophylaxis and the relative effectiveness of vaccine compared to immunoglobulin.

Neuraminidase inhibitors for preventing and treating influenza in adults and children.

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza-infected and non-influenza-infected subgroups (P = 0.53). Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI -0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported. Serious influenza complications or those leading to study withdrawal. In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI -0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children. Pneumonia. Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator-mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir. Bronchitis, sinusitis and otitis media. Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children. Harms of treatment. Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four-fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I(2) statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on-treatment period. There was a dose-response effect on psychiatric events in the two oseltamivir "pivotal" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four-fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I(2) = 0%). Prophylaxis. In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non-influenza, influenza-like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI -2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.

Ecological study estimating melanoma overdiagnosis in the USA using the lifetime risk method.

OBJECTIVES: To quantify the proportion of melanoma diagnoses (invasive and in situ) in the USA that might be overdiagnosed. DESIGN: In this ecological study, incidence and mortality data were collected from the Surveillance, Epidemiology and End Results 9 registries database. DevCan software was used to calculate the cumulative lifetime risk of being diagnosed with melanoma between 1975 and 2018, with adjustments made for changes in longevity and risk factors over the study period. SETTING: USA. PARTICIPANTS: White American men and women (1975-2018). MAIN OUTCOME MEASURES: The primary outcome was excess lifetime risk of melanoma diagnosis between 1976 and 2018 (adjusted for year 2018 competing mortality and changes in risk factors), which was inferred as likely overdiagnosis. The secondary outcome was an excess lifetime risk of melanoma diagnosis in each year between 1976 and 2018 (adjusted and unadjusted). RESULTS: Between 1975 and 2018 the adjusted lifetime risk of being diagnosed with melanoma (invasive and in situ) increased from 3.2% (1 in 31) to 6.4% (1 in 16) among white men, and from 1.6% (1 in 63) to 4.5% (1 in 22) among white women. Over the same period, the adjusted lifetime risk of being diagnosed with melanoma in situ increased from 0.17% (1 in 588) to 2.7% (1 in 37) in white men and 0.08% (1 in 1250) to 2.0% (1 in 50) in white women. An estimated 49.7% of melanomas diagnosed in white men and 64.6% in white women were overdiagnosed in 2018. Among people diagnosed with melanomas in situ, 89.4% of white men and 85.4% of white women were likely overdiagnosed in 2018. CONCLUSIONS: Melanoma overdiagnosis among white Americans is significant and increasing over time with an estimated 44 000 overdiagnosed in men and 39 000 in women in 2018. A large proportion of overdiagnosed melanomas are in situ cancers, pointing to a potential focus for intervention.

Characteristics of exceptionally good Doctors-A survey of public adults.

Background: Systematic reviews have found that doctors can have a substantial effect on patients' physical health, beyond what can be explained by known factors. In a previous qualitative study, 13 medical doctors were interviewed on their experiences of exceptionally good doctors, and all had met at least one such doctor. Objective: To determine how common it is for exceptionally good doctors to be encountered by patients and what are the characteristics of exceptionally good doctors. Design: Mixed methods cross-sectional survey of 580 Amazon Mechanical Turk participants. Questions included doctor and participant demographics, and 34 Likert questions on characteristics of exceptionally good and average doctors. Free-text questions allowed participants to describe exceptional doctors, record their experience, and provide survey feedback. Stratified sampling ensured gender parity and 33% of participants aged ≥55 years. Analysis included descriptive statistics, statistical modelling of associations between Likert scale scores and patient demographics, and factor analysis. Results: Of 580 responses, 505 (86%) were included in the analysis. Factor analysis confirmed internal validity. Most respondents (86%) had met at least two exceptionally good doctors, of whom 55% were specialists. 58% of respondents regarded doctors as exceptional based on an overall impression with multiple reasons. Doctors were most commonly considered exceptional based on one or more of their personality, diagnostic, or intervention ability. Respondents who reported the doctors "willingly listened to them to the end" scored their doctors higher on 33 of 34 Likert questions, except for popularity. They also rated average doctors lower throughout. Conclusions: Exceptionally good doctors appear to be commonly encountered by the adult public. Listening to patients willingly to the end is a highly rated and influential characteristic, suggesting that listening could be targeted for quality improvement.

Understanding African American vernacular English and reading achievement: Implications for the science of reading.

The purpose of this article is to discuss issues of language, specifically African American Vernacular English (AAVE), as it relates to the reading performance of African American children. Previous research on the science of reading provides a research-based framework that is a starting point for evidence-based research that can be used to improve the reading outcomes of African American children. School psychology literature is limited in its inclusion of issues posed by deficit perspectives of AAVE with Black children and reading achievement. Given that practicing school psychologists spend significant portions of their time conducting assessments related to identifying and remediating reading problems, an increased awareness on how AAVE can impact African American children's reading performance is necessary. Implications for research and practice will be discussed, such as inclusion of instruments to differentiate between reading difficulties and dialect differences (i.e., Diagnostic Evaluation of Language Variation). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Uterine atony prophylaxis with carbetocin versus oxytocin and the risk of major haemorrhage during caesarean section: A retrospective cohort study.

Carbetocin and oxytocin are commonly recommended agents for active management of the third stage of labour. Evidence is inconclusive whether either one more effectively reduces the occurrence of important postpartum haemorrhage outcomes at caesarean section. We examined whether carbetocin is associated with a lower risk of severe postpartum haemorrhage (blood loss ≥ 1000 ml) in comparison with oxytocin for the third stage of labour in women undergoing caesarean section. This was a retrospective cohort study among women undergoing scheduled or intrapartum caesarean section between 1 January 2010 and 2 July 2015 who received carbetocin or oxytocin for the third stage of labour. The primary outcome was severe postpartum haemorrhage. Secondary outcomes included blood transfusion, interventions, third stage complications and estimated blood loss. Outcomes were examined overall and by timing of birth, scheduled versus intrapartum, using propensity score-matched analysis. Among 21,027 eligible participants, 10,564 women who received carbetocin and 3836 women who received oxytocin at caesarean section were included in the analysis. Carbetocin was associated with a lower risk of severe postpartum haemorrhage overall (2.1% versus 3.3%; odds ratio, 0.62; 95% confidence interval 0.48 to 0.79; P < 0.001). This reduction was apparent irrespective of timing of birth. Secondary outcomes also favoured carbetocin over oxytocin. In this retrospective cohort study, the risk of severe postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean section. Randomised clinical trials are needed to further investigate these findings.

Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination.

BACKGROUND: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination. METHODS: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.1 of threshold of detection). PCR-RFLP analysis was used to identify the FUT2 'G428A' mutation in a subset. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL. RESULTS: Of 156 children, 119 (76 %) were secretors, 129 (83 %) were Lewis antigen positive, and 105 (67 %) were rotavirus IgA seropositive. Eighty-seven of 119 (73 %) secretors were rotavirus seropositive, versus 4/9 (44 %) weak secretors and 13/27 (48 %) non-secretors. CONCLUSIONS: Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive to rotavirus antibodies following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain underperformance of rotavirus vaccines among Australian Aboriginal children.

Health-related quality of life changes associated with buprenorphine treatment for opioid dependence.

BACKGROUND: Few studies have described improvement in health-related quality of life (HRQOL) associated with opioid dependence treatment with buprenorphine (ODT-B). OBJECTIVE: To evaluate HRQOL changes in domain scores, physical and mental component summaries, and health utilities (HUs) associated with ODT-B using the Short Form 36 (SF-36). METHODS: We assessed HRQOL changes in a substudy of a pharmacokinetic study that compared buprenorphine oral tablet and liquid dosage formulations over 16 weeks. Individuals, aged 18-65 years, were screened for opioid dependence. They were excluded if they would not agree to birth control or had a serious medical condition. Subjects received psychosocial counseling and weekly group therapy. The SF-36 was administered upon enrollment and at 4-week intervals. We used the SF-6D to estimate HUs. We performed intention to treat (ITT) analyses based on the last observation available for each subject. Paired t tests of each domain and HU, limited to remaining patients at each 4-week interval, were also conducted. RESULTS: Of 96 subjects enrolled, cumulative dropouts over time resulted in 80, 69, 59, and 44 subjects remaining at 4, 8, 12, and 16 weeks. There were no significant differences in opioid-positive urines, dropout rates, or dosage changes between formulations. In the ITT analyses, HRQOL improvements over time were bodily pain (62.1 vs. 69.1, P = 0.017), vitality (49.8 vs. 56.5, P = 0.001), mental health (59.9 vs. 66.0, P = 0.001), social function (66.4 vs. 74.7, P = 0.001), role emotional (59.4 vs. 71.9, P = 0.003), role physical (60.9 vs. 70.6, P = 0.005), and mental component summary (41.9 vs. 45.4, P<0.001). HU scores also improved (0.674 vs. 0.715, P = 0.001). Results from paired t tests, with only concurrently enrolled patients, showed similar improvements from baseline to 4, 8, 12, or 16 weeks. CONCLUSION: Buprenorphine, accompanied with psychosocial counseling, was associated with improved HRQOL and HUs.