A population-based, province-wide, record-linkage interrupted time series analysis of impact of the universal seasonal influenza vaccination policy on seasonal influenza vaccine uptake among 5-64-year-olds in the province of Manitoba, Canada.

INTRODUCTION: Universal seasonal influenza vaccination policy (USIVP) was introduced in Manitoba, Canada in 2010. Its impact on seasonal influenza vaccine (SIV) uptake remains underexplored. METHODS: We used population-wide data from Manitoba to assess the impact of the USIVP on SIV uptake. The study covered twenty influenza seasons (2000/01-2019/20). We summarized SIV uptake for influenza seasons before and after the USIVP. Utilizing a single-group interrupted time series analysis and appropriately accounting for autocorrelation, we estimated absolute change and annual trend in SIV uptake percentages among 5-17-, 18-44-, and 45-64-year-olds across strata of certain population socioeconomic and health-related characteristics following the USIVP. RESULTS: Average SIV uptake percentage in all age groups was significantly higher after compared with before the USIVP. Following the USIVP, there was no significant absolute change in SIV uptake percentage among 18-44- and 45-64-year-olds overall; however, a significant decrease was observed among 18-44-year-old males in the higher income quintiles, across healthcare utilization, and in some regions of residence. A significant increase was observed among 5-17-year-olds in the lowest income quintiles, in Northern Manitoba, and among those with less healthcare utilization, and no chronic disease. Overall, there was mostly no significant annual trend in SIV uptake percentage among 18-44-year-olds, and while a significant upward and downward trend was observed among 5-17-year-olds and 45-64-year-olds, respectively, a significant downward trend was observed across all strata of population characteristics within all age groups in Northern Manitoba. CONCLUSIONS: The USIVP in Manitoba was followed by an absolute increase in SIV uptake percentage only in some socioeconomically disadvantaged subpopulations among 5-17-year-olds. While there was mostly an upward annual trend in SIV uptake percentage among 5-17-year-olds, a downward trend was observed among 45-64-year-olds and across all age groups and subpopulations in socioeconomically disadvantaged Northern Manitoba. These findings are novel for Manitoba and require investigation and public health attention.

Characteristics and determinants of seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage study.

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba. Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01-2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals. Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5-17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18-44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45-64-year-olds receiving the SIV in 2000-2004, 2005-2009, 2010-2014 and 2015-2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex. Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions.

A global systematic evidence review with meta-analysis of the epidemiological characteristics of the 2022 Mpox outbreaks.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarized published full-text epidemiological data from the outbreaks. METHODS: A global evidence review (protocol: osf.io/j3kb7) with systematic literature search up to February 09, 2023. We focused on experimental/observational studies of laboratory confirmed Mpox, excluding case reports and case series of < 5 cases. Epidemiological data were pooled using an inverse variance, random-effects model, and pooled estimates presented with associated 95% confidence intervals. RESULTS: We included 66 studies. Mean incubation period was 7.8 days (6.6-9.0 days, 8 studies: 560 cases), reproductive number 1.8 (1.7-1.9, 6 studies), mean duration from symptom onset to diagnosis 5.8 days (4.8-6.8 days, 4 studies: 982 cases), mean symptom duration 17.5 days (14.7-20.2 days, 3 studies: 292 cases), mean serial interval 8.5 days (7.3-9.9 days, 1 study), hospitalisation 6% (4-9%, 26 studies: 5339 cases), and vaccine effectiveness 78% (65-91%, 3 studies: 953 cases). Highly relevant clinical manifestations were pleomorphic skin lesions 82% (68-94%, 26 studies: 4093 cases), anogenital lesions 64% (51-77%, 9 studies: 10,398 cases), fever 54% (50-57%, 52 studies: 25,992 cases), and lymphadenopathy 51% (46-57%, 42 studies: 17,803 cases), with cases mostly men who have sex with men (MSM). Possibly relevant manifestations were perianal lesions, fatigue, asthenia, myalgia, and headache. CONCLUSIONS: The 2022 Mpox outbreaks presented with sex-related clinical manifestations and were mostly reported among MSM.

Impact of the universal seasonal influenza vaccination policy in the province of Manitoba, Canada: A population-based, province-wide record-linkage study.

INTRODUCTION: In 2010, the government of the province of Manitoba, Canada introduced universal seasonal influenza vaccination policy (USIVP), providing free-of-charge vaccination to all registered residents of the province at least six months of age. Impact of the policy on seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba remains unclear, as there is a lack of published evaluations. METHODS: We conducted an ecological study, utilizing population-wide data from several linked de-identified Manitoba Health and Seniors Care administrative health databases. The study period was from 2000/01-2019/20 influenza seasons. The primary exposure was USIVP (five influenza seasons pre-policy [2005/06-2009/10] compared with post-policy [2010/11-2014/15]). The outcome was SIV uptake. We conducted pre/post logistic regression analysis stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and certain population socioeconomic and health-related characteristics. Results are adjusted odds ratios with associated 95 % confidence intervals. RESULTS: We observed significantly increased adjusted odds of SIV uptake post-policy relative to pre-policy in all age groups except ≥65-year-olds already covered from inception of the vaccination programme. The adjusted odds ratios ranged from 0.76 (0.75-0.76) among ≥65-year-olds to 2.15 (2.13-2.18) among 5-17-year-olds, and were largely homogeneous within age groups across sex, income quintiles, regions of residence, and categories of number of visits to primary care physician/hospitalization one year prior to an influenza season except among <5- and 5-17-year-olds. These findings were mostly consistent irrespective of sex and region of residence although there was variability across income quintiles in Northern Manitoba region. CONCLUSIONS: Introduction of the USIVP in Manitoba was followed by a significant increase in SIV uptake in the five years post policy among <65-year-olds, with similar increased relative odds of vaccination observed within age groups across subpopulations. The observed variations in the relative odds of vaccination across income quintiles in Northern Manitoba region requires administrative attention.

Comparative evaluation of the clinical presentation and epidemiology of the 2022 and previous Mpox outbreaks: a rapid review and meta-analysis.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarised and compared the findings from published observational studies on the clinical presentation and epidemiology of the 2022 and previous outbreaks of Mpox. METHODS: We registered a review protocol with the Open Science Framework (osf.io/j3kb7). We searched MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases, and relevant websites up to August 30, 2022. Retrieved literature citations were screened for eligibility, and summary clinical presentation and epidemiological data from the included studies were pooled, when possible, using an inverse variance, random-effects model. RESULTS: Seventy-nine studies met the eligibility. Irrespective of outbreak, fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat were potentially highly relevant Mpox manifestations, while conjunctivitis, cough, and possibly reactivation of varicella zoster virus may be part of the clinical presentation. The mean incubation period for the 2022 outbreaks was 7.4 d (6.4-8.4 d, I2 64.2%; 4 studies: 270 cases) and for previous outbreaks, 12.9 d (10.4-15.5 d; one study: 31 cases), p < .001. None of the male cases from previous outbreaks was reported to have sex with men (MSM) whereas almost all reported male cases from the 2022 outbreak were MSM. Concomitant sexually transmitted infections and perianal lesions were reported only among male cases from the 2022 outbreak, with the cases mostly presenting with genital lesions. CONCLUSIONS: The 2022 Mpox outbreaks appear to be mostly among MSM and have a lower incubation period compared with previous outbreaks.Key messages79 studies met the review's inclusion criteria.The 2022 Mpox outbreaks appear to have shorter incubation period compared with previous outbreaks.Established clinical presentation of Mpox includes fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat.Almost all reported cases from the 2022 Mpox outbreaks were men who had sex with men (MSM).Concomitant sexually transmitted infections and perianal lesions were only reported among cases from the 2022 Mpox outbreaks.A significantly higher proportion of Mpox cases from the 2022 outbreaks had genital lesions compared with cases from previous outbreaks.The 2022 Mpox outbreaks appear to be mostly among MSM.

Self-Management Programs for Chronic Non-Cancer Pain: A Rapid Review of Randomized Trials.

BACKGROUND: The body of evidence regarding self-management programs (SMPs) for adult chronic non-cancer pain (CNCP) is steadily growing, and regular updates are needed for effective decision-making. OBJECTIVES: To systematically identify, critically appraise, and summarize the findings from randomized controlled trials (RCTs) of SMPs for CNCP. METHODS: We searched relevant databases from 2009 to August 2021 and included English-language RCT publications of SMPs compared with usual care for CNCP among adults (18+ years old). The primary outcome was health-related quality of life (HR-QoL). We conducted meta-analysis using an inverse variance, random-effects model and calculated the standardized mean difference (SMD) and associated 95% confidence interval (CI) and statistical heterogeneity using the I2 statistic. RESULTS: From 8538 citations, we included 28 RCTs with varying patient populations, standards for SMPs, and usual care. No RCTs were classified as having a low risk of bias. There was no evidence of a significant improvement in overall HR-QoL, irrespective of pain type, immediately post-intervention (SMD 0.01, 95%CI -0.21 to 0.24; I2 57%; 11 RCTs; 979 participants), 1-4 months post-intervention (SMD 0.02, 95%CI -0.16 to 0.20; I2 48.7%; 12 RCTs; 1160 participants), and 6-12 months post-intervention (SMD 0.07, 95%CI -0.06 to 0.21; I2 26.1%; 9 RCTs; 1404 participants). Similar findings were made for physical and mental HR-QoL, and for specific QoL assessment scales (e.g., SF-36). CONCLUSIONS: There is a lack of evidence that SMPs are efficacious for CNCP compared with usual care. Standardization of SMPs for CNCP and better planned/conducted RCTs are needed to confirm these conclusions.

Characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy and/or effectiveness of influenza vaccines: an overview of reviews.

BACKGROUND: While systematic reviews (SR) generally suggest that vaccination is an effective way to prevent influenza infection, it is not clear if these conclusions are based on high quality SR methods. As such, we systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza vaccines. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 11, 2022. We summarised the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From 11,193 retrieved citations, we included 48 publications (47 SRs). Seventy-five percent were of a critically low quality, 19% of a low quality, 2% of a moderate quality, and 4% of a high quality. Thirteen percent were industry-funded, about 13% co-authored by industry employee(s), and 4% commissioned by an organisation or authority. Only 45% percent reported protocol registration, 6% reported collaboration with a knowledge synthesis librarian/information specialist, and 60% utilised a reporting checklist (e.g. PRISMA). CONCLUSIONS AND RELEVANCE: SRs with meta-analysis of efficacy/effectiveness of influenza vaccines are mostly of critically low quality and even the more recent reviews did not follow current best SR practices. These findings are significant in view of the controversies that surround influenza vaccines, and the use of SRs in informed decision-making. However, the findings do not justify curtailment or cessation of influenza vaccine use as vaccines continue to offer substantial net public health benefit.HighlightsWe systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in 47 systematic reviews with meta-analysis of efficacy/effectiveness of influenza vaccines.13% of the reviews were industry-funded.About 13% of the reviews were co-authored by industry employee(s).4% of the reviews were commissioned by an organisation/authority.45% of the reviews reported protocol registration.6% of the reviews reported collaborating with a knowledge synthesis librarian/information specialist to prepare the search strategy.60% of the reviews reported using the PRISMA (or similar) checklist.75% of the reviews were judged to be of critically low quality; 19% of low quality; 2% of moderate quality; 4% of high quality.

An overview of the characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy/effectiveness of influenza antiviral drugs.

BACKGROUND: Influenza antiviral drugs remain controversial and it is not clear if conclusions on their efficacy/effectiveness are based on high quality systematic reviews (SRs). We systematically identified, critically appraised, and summarized the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza antiviral drugs for prevention and/or treatment of influenza. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 2020. We summarized the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From a total 3,898 citations after removal of duplicates from all identified citations, we included 24 SRs. Seventy-five percent (n = 18) were of a critically low quality, 8% (n = 2) of a low quality, 17% (n = 4) of a moderate quality, and none were of a high quality. Seventeen percent (n = 4) were industry-funded, 4% (n = 1) coauthored by industry employee(s), and 33% (n = 8) commissioned by an organization or authority. Only 33% percent (n = 8) reported protocol registration, 4% (n = 1) reported collaboration with a knowledge synthesis librarian/information specialist, and 17% (n = 4) utilized a systematic review reporting checklist. CONCLUSIONS: The evidence suggests that SRs of efficacy/effectiveness of influenza antiviral drugs are mostly of critically low quality and do not follow current best SR practices. These findings are significant in view of the important role of SRs in decision-making and the controversies that surround the use of the influenza antiviral drugs. However, the findings should not be interpreted to mean curtailment/cessation of use of antiviral drugs for influenza.

Correlation between country-level numbers of COVID-19 cases and mortalities, and country-level characteristics: A global study.

Background: Not much is known about correlations between country-level characteristics and country-level numbers of COVID-19 cases and mortalities. Methods: Using data from the World Health Organization and other international organisations, we summarised country-level COVID-19 case and mortality counts per 100,000 population, and COVID-19 case fatality rate from January 2020 to August 2021. We conducted adjusted linear regression analysis to assess relationships between these counts/rate and certain country-level characteristics. We reported adjusted regression coefficients, ß and associated 95% confidence intervals. Results: There was a positive correlation between the number of cases and country-level male/female ratio, and positive correlations between the numbers of cases and mortalities and country-level proportion of 60+-year-olds, universal health coverage index of service coverage (UHC) and tourism. Country economic status correlated negatively with the numbers of cases and mortalities. COVID-19 case fatality rate was highest in Peru, South American region (9.2%), and lowest in Singapore, Western Pacific region (0.1%). A negative correlation was observed between case fatality rate and country-level male/female ratio, population density and economic status. These observations remained mostly among mid-/low-income countries, particularly a positive correlation between the number of cases and male/female ratio and proportion of 60+-year-olds. Conclusions: Various country-level characteristics such as male/female ratio, proportion of older adults, country economic status, UHC and tourism appear to be correlated with the country-level number of COVID-19 cases and/or mortalities. Consideration of these characteristics may be necessary when designing country-level COVID-19 epidemiological studies and in comparing COVID-19 data between countries.

Offloading devices for neuropathic foot ulcers in adult persons with type 1 or type 2 diabetes: a rapid review with meta-analysis and trial sequential analysis of randomized controlled trials.

INTRODUCTION: Healing time for neuropathic planter foot ulcers (NPFUs) in persons with diabetes may be reduced through use of non-removable fiberglass total contact casting (F-TCC) compared with removable cast walkers (RCWs), although the evidence base is still growing. RESEARCH DESIGN AND METHODS: We conducted a rapid review and systematically searched for, and critically assessed, randomized controlled trials (RCTs) that compared the efficacy of F-TCC versus RCW, focusing on the time to ulcer healing in adult persons (18+ years) with NPFUs and type 1 or type 2 diabetes. We meta-analysed the mean differences and associated 95% CIs using an inverse variance, random-effects model. We also conducted a trial sequential analysis (TSA) to assess if the available evidence is up to the required information size for a robust conclusion. We assessed and quantified statistical heterogeneity between the included studies using the I2 statistic. RESULTS: Out of 102 retrieved citations, five RCTs met the eligibility criteria. Participants' inclusion in relation to stage of ulcer was highly variable as was peripheral neuropathy complicating comparisons. F-TCC appeared to present a shorter ulcer healing time (-5.42 days, 95% CI -9.66 days to -1.17 days; I2 9.9%; 5 RCTs; 169 participants) compared with RCW. This finding was supported by the TSA. CONCLUSIONS: There is limited evidence from RCTs to suggest that F-TCC has a shorter ulcer healing time compared with RCW among adults with diabetic NPFUs. Properly designed and conducted RCTs are still required for a stronger evidence base.

Implementing High-Quality Primary Care Through a Health Equity Lens.

The COVID-19 pandemic highlighted the importance of centering health equity in future health system and primary care reforms. Strengthening primary care will be needed to correct the longstanding history of mistreatment of First Nations/Indigenous and racialized people, exclusion of health care workers of color, and health care access and outcome inequities further magnified by the COVID-19 pandemic. The National Academies of Sciences, Engineering, and Medicine (NASEM) released a report on Implementing High-Quality Primary Care: Rebuilding the Foundation of Health Care, that provided a framework for defining high-quality primary care and proposed 5 recommendations for implementing that definition. Using the report's framework, we identified health equity challenges and opportunities with examples from primary care systems in the United States and Canada. We are poised to reinvigorate primary care because the recent pandemic and the attention to continued racialized police violence sparked renewed conversations and collaborations around equity, diversity, inclusion, and health equity that have been long overdue. The time to transition those conversations to actionable items to improve the health of patients, families, and communities is now.Appeared as Annals "Online First" article.

Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis.

BACKGROUND: To better inform clinical practice, we summarized the findings from randomized controlled trials (RCTs) of antivirals for COVID-19. METHODS: We systematically searched for literature up to September 2020, and included English-language publications of RCTs among hospitalized COVID-19 patients. We conducted network meta-analysis combining results of both the direct and indirect comparisons of interventions. The efficacy outcomes were clinical progression, all-cause mortality, and viral clearance, and safety outcomes were diarrhea, nausea, and vomiting. We generated treatment rankings (best to worst) and summarized rank probabilities using rankogram. RESULTS: We included 15 RCTs (14,418 patients) from 7,237 retrieved citations. There was no evidence for efficacy of the assessed antivirals compared with placebo/no treatment or with another antiviral for all efficacy outcomes. Lopinavir (400 mg)/ritonavir (100 mg) significantly increased diarrhea, nausea, and vomiting compared with placebo/no treatment and other antivirals, and was ranked worst for these outcomes, while triazavirin (250 mg), baloxavir marboxil (80 mg), and remdesivir (100 mg - 10 days) ranked best, respectively. CONCLUSIONS AND RELEVANCE: The available evidence does not support the use of any antiviral drugs for COVID-19. Cautious interpretations of the findings are, however, advised considering the paucity of the evidence. More RCTs are needed for a stronger evidence base.

The Number Needed to Vaccinate (NNV) against herpes zoster: a systematic review with meta-analysis.

OBJECTIVES: The number needed to vaccinate (NNV) quantifies the effectiveness of vaccination programs. We summarised the published data on NNV against herpes zoster to inform vaccination policies. METHODS: We systematically identified studies based on a priori established and registered methods. The main outcomes were the NNV against herpes zoster infection, hospitalisation and mortality. Where appropriate, we conducted meta-analyses using inverse variance, random-effects models, pooling estimated NNV with associated 95% confidence interval (CI). Statistical heterogeneity between pooled estimates was calculated using the I2 statistic. RESULTS: Out of 229 unique citations, we included eight nonrandomized studies. Among 50+ year-olds, the NNV against herpes zoster infection using the recombinant subunit vaccine was 11 (95%CI 8-14; I2 = 0%; 3 studies) and variable (I2 = 94.4%; 7 studies) using live attenuated vaccine, ranging from 10 (95%CI 1-19) to 58 (95%CI 49-67). Among 65+ year-olds, the NNV against herpes zoster infection using the recombinant subunit vaccine was 12 (95%CI: 9-15; I2 = 0%; 2 studies) and variable (I2 = 98.5%; 4 studies) using live attenuated vaccine, ranging from 14 (95%CI 5-23) to 75 (95%CI 66-84). The NNV against herpes zoster hospitalisation among 65+ year-olds using the live attenuated vaccine was 280 (95%CI 209-352; I2 = 0%; 2 studies). There was a paucity of data to inform other meta-analyses. CONCLUSION: Evidence on the NNV against herpes zoster is scarce. Vaccination with the recombinant subunit herpes zoster vaccine may be more effective than with the live attenuated vaccine in preventing infection among 50+ year-olds. More studies are needed for a stronger evidence base for decision-making.

Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis.

The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised, and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), and Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with the National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2  statistic. From 2875 screened citations, we included 12 studies (1255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95% CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.

Interventions to improve early cancer diagnosis of symptomatic individuals: a scoping review.

OBJECTIVES: To summarise the current evidence regarding interventions for accurate and timely cancer diagnosis among symptomatic individuals. DESIGN: A scoping review following the Joanna Briggs Institute's methodological framework for the conduct of scoping reviews and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SOURCES: MEDLINE (Ovid), CINAHL (EBSCOhost) and PsycINFO (Ovid) bibliographic databases, and websites of relevant organisations. Published and unpublished literature (grey literature) of any study type in the English language were searched for from January 2017 to January 2021. ELIGIBILITY AND CRITERIA: Study participants were individuals of any age presenting at clinics with symptoms indicative of cancer. Interventions included practice guidelines, care pathways or other initiatives focused on achieving predefined benchmarks or targets for wait times, streamlined or rapid cancer diagnostic services, multidisciplinary teams and patient navigation strategies. Outcomes included accuracy and timeliness of cancer diagnosis. DATA EXTRACTION AND SYNTHESIS: We summarised findings graphically and descriptively. RESULTS: From 21 298 retrieved citations, 88 unique published articles and 16 unique unpublished documents (on 18 study reports), met the eligibility for inclusion. About half of the published literature and 83% of the unpublished literature were from the UK. Most of the studies were on interventions in patients with lung cancer. Rapid referral pathways and technology for supporting and streamlining the cancer diagnosis process were the most studied interventions. Interventions were mostly complex and organisation-specific. Common themes among the studies that concluded intervention was effective were multidisciplinary collaboration and the use of a nurse navigator. CONCLUSIONS: Multidisciplinary cooperation and involvement of a nurse navigator may be unique features to consider when designing, delivering and evaluating interventions focused on improving accurate and timely cancer diagnosis among symptomatic individuals. Future research should examine the effectiveness of the interventions identified through this review.

Efficacy and safety of clinically managed weight loss programs: a systematic review and meta-analysis protocol.

BACKGROUND: Obesity has become a major driver in the burden of chronic diseases. The Canadian Clinical Practice Guidelines recommend a lifestyle intervention for the management and prevention of obesity. This includes behavior modification, dietary counseling, and physical activity. With the market overwhelmed with weight loss programs, the majority are focused on low-calorie diets and general recommendations for exercise. Most are not personalized and are not administered by healthcare professionals. An interdisciplinary team of highly trained healthcare professionals has the ability to provide medically sound and safe advice in all aspects of an individuals' life, such as lifestyle, sleep, mental health, and behaviors. A clinically managed weight loss program is defined as a team including a dietitian, exercise professional, psychologist, and/or physician or nurse practitioner oversight. With limiting results in the literature regarding clinically managed weight loss programs, it is difficult to conclude whether it may be effective. Therefore, the objective of this systematic review is to assess clinically managed weight loss programs, with a physician or nurse practitioner oversight in comparison with non-clinically managed weight loss programs with no physician oversight or nurse practitioner oversight in adults who are living with overweight or obesity. METHODS: A literature search will be executed by a knowledge synthesis librarian on MEDLINE, Cochrane Central, Embase, PsycINFO, and CINAHL. The data collected will be extracted, stored, and managed in MS Excel 2016. The extraction of the data will include study details, study population details, health team details, intervention details, and outcome details. DISCUSSION: The prevalence of obesity has been increasing throughout the decades. The results from this systematic review may aid in recommending a more clinically safe weight loss program for those who struggle with overweight or obesity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170014.

Remdesivir for coronavirus disease 2019 (COVID-19): a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: In view of many unanswered clinical questions regarding treatment of COVID-19 with remdesivir, we systematically identified, critically appraised and summarized the findings from randomized controlled trials (RCTs) of remdesivir for COVID-19. METHODS: We searched relevant databases/websites (up to September 2020) and selected English-language RCT publications of remdesivir for COVID-19. We conducted meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA) for the efficacy outcomes: all-cause mortality, viral burden and clinical progression. Safety outcomes were diarrhoea, nausea, and vomiting. We calculated the relative risk (RR) and 95% confidence interval (CI) for all outcomes. Statistical heterogeneity was calculated using the I2 statistic. RESULTS: We included five RCTs (7540 participants) from 7237 citations. Most (80%) were of an unclear to high risk of bias. There was no evidence of a significant improvement with remdesivir (100 mg, 10 days) regarding all-cause mortality (RR 0.94, CI 0.82-1.07; I2 = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; I2 = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; I2 = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; I2 = 0%; 2 RCTs; 630 patients). TSA showed that the required information size was not reached for firm conclusions to be drawn. CONCLUSIONS AND RELEVANCE: There is insufficient evidence to support the use of remdesivir for treatment of COVID-19. More high-quality RCTs are needed for a stronger evidence. Until then, remdesivir should remain an experimental drug for COVID-19.

Implementation strategies in emergency management of children: A scoping review.

BACKGROUND: Implementation strategies are vital for the uptake of evidence to improve health, healthcare delivery, and decision-making. Medical or mental emergencies may be life-threatening, especially in children, due to their unique physiological needs when presenting in the emergency departments (EDs). Thus, practice change in EDs attending to children requires evidence-informed considerations regarding the best approaches to implementing research evidence. We aimed to identify and map the characteristics of implementation strategies used in the emergency management of children. METHODS: We conducted a scoping review using Arksey and O'Malley's framework. We searched four databases [Medline (Ovid), Embase (Ovid), Cochrane Central (Wiley) and CINAHL (Ebsco)] from inception to May 2019, for implementation studies in children (≤21 years) in emergency settings. Two pairs of reviewers independently selected studies for inclusion and extracted the data. We performed a descriptive analysis of the included studies. RESULTS: We included 87 studies from a total of 9,607 retrieved citations. Most of the studies were before and after study design (n = 68, 61%) conducted in North America (n = 63, 70%); less than one-tenth of the included studies (n = 7, 8%) were randomized controlled trials (RCTs). About one-third of the included studies used a single strategy to improve the uptake of research evidence. Dissemination strategies were more commonly utilized (n = 77, 89%) compared to other implementation strategies; process (n = 47, 54%), integration (n = 49, 56%), and capacity building and scale-up strategies (n = 13, 15%). Studies that adopted capacity building and scale-up as part of the strategies were most effective (100%) compared to dissemination (90%), process (88%) and integration (85%). CONCLUSIONS: Studies on implementation strategies in emergency management of children have mostly been non-randomized studies. This review suggests that 'dissemination' is the most common strategy used, and 'capacity building and scale-up' are the most effective strategies. Higher-quality evidence from randomized-controlled trials is needed to accurately assess the effectiveness of implementation strategies in emergency management of children.

Decline in Seasonal Influenza Vaccine Effectiveness With Vaccination Program Maturation: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence suggests that repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (PM; number of years since program inception) as a proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies. METHODS: We systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles and calculated pooled VE using an inverse-variance random-effects model. The primary outcome was pooled VE against all influenza. RESULTS: We included 72 articles from 11 931 citations. Across the 3 categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2), and influenza B. CONCLUSIONS: The evidence suggests that influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE.

Interim seasonal influenza vaccine effectiveness estimates as proxy for final estimates: analysis of systematically identified matched pairs of interim/final estimates from test-negative design studies in outpatient settings from 2010/11 to 2018/19.

OBJECTIVES: Limited time for seasonal influenza vaccine development means that the World Health Organization has to consider interim (early) rather than final vaccine effectiveness (VE) estimates in deciding influenza vaccine composition. We assessed agreement between interim and final VE estimates, and factors that may determine a substantial difference (≥10%) between point estimates. METHODS: This was a mixed methods study. We systematically searched, identified, and matched interim/final VE studies of test-negative design (TND) type in outpatient settings after the 2009/10 influenza pandemic. The chi-square statistic (χ2) was used to assess the statistical significance of the difference between paired interim/final VE estimates. We calculated the difference between point estimates and used multivariable logistic regression to assess factors that may determine a substantial difference. RESULTS: We identified 68 interim/final VE pairs. There was no statistically significant difference between almost all compared pairs. An inconsistent statistical model for interim/final VE estimation and interim VE estimation before the epidemic peak increased the odds of having a substantial difference between estimates. CONCLUSION: : Interim influenza VE appears to be sufficient for vaccine composition decision-making. Consistency in interim/final VE estimation, and interim VE estimation during/after epidemic peak may increase agreement between the VE estimates.