Nirmatrelvir/Ritonavir Regimen for Mild/Moderately Severe COVID-19: A Rapid Review With Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear. METHODS: We systematically identified randomized controlled trials (RCTs) and real-world studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the I 2 statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/study quality and conducted trial sequential analysis of the evidence from RCTs. RESULTS: We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged ≥18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID-19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; I 2 = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; I 2 = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; I 2 = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; I 2 = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; I 2 = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; I 2 = 49.9%; 3 RCTs, 3,806 persons), although trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; I 2 = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; I 2 = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment. CONCLUSIONS: Nirmatrelvir/ritonavir appears to be promising for preventing hospitalization and potentially decreasing all-cause mortality for persons with mild/moderately severe COVID-19, but the evidence is weak. More studies are needed.

The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. RESULTS: There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67). CONCLUSION: Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.

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.

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.

Searching for evidence in public health emergencies: a white paper of best practices.

Objectives: Information professionals have supported medical providers, administrators and decision-makers, and guideline creators in the COVID-19 response. Searching COVID-19 literature presented new challenges, including the volume and heterogeneity of literature and the proliferation of new information sources, and exposed existing issues in metadata and publishing. An expert panel developed best practices, including recommendations, elaborations, and examples, for searching during public health emergencies. Methods: Project directors and advisors developed core elements from experience and literature. Experts, identified by affiliation with evidence synthesis groups, COVID-19 search experience, and nomination, responded to an online survey to reach consensus on core elements. Expert participants provided written responses to guiding questions. A synthesis of responses provided the foundation for focus group discussions. A writing group then drafted the best practices into a statement. Experts reviewed the statement prior to dissemination. Results: Twelve information professionals contributed to best practice recommendations on six elements: core resources, search strategies, publication types, transparency and reproducibility, collaboration, and conducting research. Underlying principles across recommendations include timeliness, openness, balance, preparedness, and responsiveness. Conclusions: The authors and experts anticipate the recommendations for searching for evidence during public health emergencies will help information specialists, librarians, evidence synthesis groups, researchers, and decision-makers respond to future public health emergencies, including but not limited to disease outbreaks. The recommendations complement existing guidance by addressing concerns specific to emergency response. The statement is intended as a living document. Future revisions should solicit input from a broader community and reflect conclusions of meta-research on COVID-19 and health emergencies.

Preoperative oral fluoroquinolone antibiotics in elective colorectal surgery to prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. METHODS: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials( Ovid) and ClinicalTrials.gov. RESULTS: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, I 2 = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, I 2 = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, I 2 = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, I 2 = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, I 2 = 0%). No antibiotic-related adverse events were reported. CONCLUSION: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens.

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.

Postoperative neurologic symptoms in the operative arm after shoulder surgery with interscalene blockade: a systematic review.

OBJECTIVE: Postoperative neurologic symptoms (PONS) in the operative arm are important complications of shoulder surgery and interscalene blockade (ISB). This systematic review aimed to compare the risk of PONS between ISB and other techniques, and the relative safety of different agents used in ISB. METHODS: Our systematic review followed Cochrane review methodology and was registered in PROSPERO. A search of MEDLINE (Ovid), EMBASE (Ovid), and CENTRAL (Wiley) from inception to June 2020 was completed. We included randomized or quasi-randomized trials of patients (> five years old) undergoing shoulder surgery with any ISB technique as an intervention, compared with any other nonregional or regional technique, or ISB of alternate composition or technique. The primary outcome was PONS (study author defined) assessed a minimum of one week after surgery. RESULTS: Fifty-five studies totalling 6,236 participants (median, 69; range, 30-910) were included. Another 422 otherwise eligible trials were excluded because PONS was not reported. Heterogeneity in when PONS was assessed (from one week to one year) and the diagnostic criteria used precluded quantitative meta-analysis. The most common PONS definition, consisting of one or more of paresthesia, sensory deficit, or motor deficit, was only used in 16/55 (29%) trials. Risk of bias was low in 5/55 (9%) trials and high in 36/55 (65%) trials, further limiting any inferences. CONCLUSION: These findings highlight the need for a standardized PONS outcome definition and follow-up time, along with routine, rigorous measurement of PONS in trials of ISB. STUDY REGISTRATION: PROSPERO (CRD42020148496); registered 10 February 2020.

RéSUMé: OBJECTIF: Les symptômes neurologiques postopératoires (SNPO) dans le bras opéré sont une complication importante des chirurgies de l'épaule sous bloc interscalénique (BIS). Cette revue systématique visait à comparer le risque de SNPO entre le BIS et d'autres techniques, ainsi que l'innocuité relative de divers agents utilisés pour réaliser un BIS. MéTHODE: Notre revue systématique a suivi la méthodologie de révision Cochrane et a été enregistrée dans le registre PROSPERO. Une recherche a été menée dans les bases de données MEDLINE (Ovid), EMBASE (Ovid) et CENTRAL (Wiley) de leur création à juin 2020. Nous avons inclus les études randomisées ou quasi-randomisées de patients (> cinq ans) bénéficiant d'une chirurgie de l'épaule avec n'importe quelle technique de BIS en tant qu'intervention, comparée à toute autre technique régionale ou non régionale, ou à un BIS de composition ou de technique alternative. Le critère d'évaluation principal était les SNPO (définis par l'auteur de l'étude) évalué au moins une semaine après la chirurgie. RéSULTATS: Cinquante-cinq études totalisant 6236 participants (médiane, 69; intervalle, 30-910) ont été incluses. Quatre cent vingt-deux autres études autrement admissibles ont été exclues parce que les SNPO n'y étaient pas rapportés. L'hétérogénéité du moment auquel les SNPO ont été évalués (d'une semaine à un an) et les critères diagnostiques utilisés ont empêché la réalisation d'une méta-analyse quantitative. La définition la plus courante des SNPO, consistant en la présence de paresthésie, de déficit sensoriel et/ou de déficit moteur, n'a été utilisée que dans 16/55 (29 %) des études. Le risque de biais était faible dans 5/55 (9 %) des études et élevé dans 36/55 (65 %) des études, limitant davantage toute autre inférence. CONCLUSION: Ces résultats soulignent la nécessité d'une définition normalisée du critère de SNPO et du temps de suivi, ainsi que la nécessité d'une mesure systématique et rigoureuse des SNPO dans les études portant sur les blocs interscaléniques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020148496); enregistrée le 10 février 2020.

Opioids and the Risk of Motor Vehicle Collision: A Systematic Review.

Background: Opioid analgesics are among the most commonly prescribed medications, but questions remain regarding their impact on the day-to-day functioning of patients including driving. We set out to perform a systematic review on the risk of motor vehicle collision (MVC) associated with prescription opioid exposure. Method: We searched Medline, PubMed, EMBASE, Scopus, and TRID from January 1990 to August 31, 2021 for primary studies assessing prescribed opioid use and MVCs. Results: We identified 14 observational studies that met inclusion criteria. Among those, 8 studies found an increased risk of MVC among those participants who had a concomitant opioid prescription at the time of the MVC and 3 found no significant increase of culpability of fatal MVC. The 3 studies that evaluated the presence of a dose-response relationship between the dose of opioids taken and the effects on MVC risk reported the existence of a dose-response relationship. Due to the heterogeneity of the different studies, a quantitative meta-analysis to sum evidence was deemed unfeasible. Our review supports increasing evidence on the association between motor vehicle collisions and prescribed opioids. This research would guide policies regarding driving legislation worldwide. Conclusion: Our review indicates that opioid prescriptions are likely associated with an increased risk of MVCs. Further studies are warranted to strengthen this finding, and investigate additional factors such as individual opioid medications, opioid doses and dose adjustments, and opioid tolerance for their effect on MVC risk.

Training programs to improve identification of sick newborns and care-seeking from a health facility in low- and middle-income countries: a scoping review.

BACKGROUND: Most neonatal deaths occur in low- and middle-income countries (LMICs). Limited recommendations are available on the optimal personnel and training required to improve identification of sick newborns and care-seeking from a health facility. We conducted a scoping review to map the key components required to design an effective newborn care training program for community-based health workers (CBHWs) to improve identification of sick newborns and care-seeking from a health facility in LMICs. METHODS: We searched multiple databases from 1990 to March 2020. Employing iterative scoping review methodology, we narrowed our inclusion criteria as we became more familiar with the evidence base. We initially included any manuscripts that captured the concepts of "postnatal care providers," "neonates" and "LMICs." We subsequently included articles that investigated the effectiveness of newborn care provision by CBHWs, defined as non-professional paid or volunteer health workers based in communities, and their training programs in improving identification of newborns with serious illness and care-seeking from a health facility in LMICs. RESULTS: Of 11,647 articles identified, 635 met initial inclusion criteria. Among these initial results, 35 studies met the revised inclusion criteria. Studies represented 11 different types of newborn care providers in 11 countries. The most commonly studied providers were community health workers. Key outcomes to be measured when designing a training program and intervention to increase appropriate assessment of sick newborns at a health facility include high newborn care provider and caregiver knowledge of newborn danger signs, accurate provider and caregiver identification of sick newborns and appropriate care-seeking from a health facility either through caregiver referral compliance or caregivers seeking care themselves. Key components to consider to achieve these outcomes include facilitators: sufficient duration of training, refresher training, supervision and community engagement; barriers: context-specific perceptions of newborn illness and gender roles that may deter care-seeking; and components with unclear benefit: qualifications prior to training and incentives and remuneration. CONCLUSION: Evidence regarding key components and outcomes of newborn care training programs to improve CBHW identification of sick newborns and care-seeking can inform future newborn care training design in LMICs. These training components must be adapted to country-specific contexts.

Interventions on health care providers to improve seasonal influenza vaccination rates among patients: a systematic review and meta-analysis of the evidence since 2000.

BACKGROUND: Seasonal influenza vaccination (SIV) rates remain suboptimal in many populations, even in those with universal SIV. OBJECTIVE: To summarize the evidence on interventions on health care providers (physicians/nurses/pharmacists) to increase SIV rates. METHODS: We systematically searched/selected full-text English publications from January 2000 to July 2019 (PROSPERO-CRD42019147199). Our outcome was the difference in SIV rates between patients in intervention and non-intervention groups. We calculated pooled difference using an inverse variance, random-effects model. RESULTS: We included 39 studies from 8370 retrieved citations. Compared with no intervention, team-based training/education of physicians significantly increased SIV rates in adult patients: 20.1% [7.5-32.7%; I2 = 0%; two randomized controlled trials (RCTs)] and 13.4% [8.6-18.1%; I2 = 0%; two non-randomized intervention studies (NRS)]. A smaller increase was observed in paediatric patients: 7% (0.1-14%; I2 = 0%; two NRS), and in adult patients with team-based training/education of physicians and nurses together: 0.9% (0.2-1.5%; I2 = 30.6%; four NRS). One-off provision of guidelines/information to physicians, and to both physicians and nurses, increased SIV rates in adult patients: 23.8% (15.7-31.8%; I2 = 45.8%; three NRS) and paediatric patients: 24% (8.1-39.9%; I2 = 0%; two NRS), respectively. Use of reminders (prompts) by physicians and nurses slightly increased SIV rates in paediatric patients: 2.3% (0.5-4.2%; I2 = 0%; two RCTs). A larger increase was observed in adult patients: 18.5% (14.8-22.1%; I2 = 0%; two NRS). Evidence from both RCTs and NRS showed significant increases in SIV rates with varied combinations of interventions. CONCLUSIONS: Limited evidence suggests various forms of physicians' and nurses' education and use of reminders may be effective for increasing SIV rates among patients.

Treatment of Uremic Pruritus: A Systematic Review.

BACKGROUND: Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. STUDY DESIGN: Systematic review. SETTING & POPULATION: Adult patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. SELECTION CRITERIA FOR STUDIES: PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. INTERVENTION: Any intervention for the treatment of uremic pruritus was included. OUTCOMES: A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale. RESULTS: 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high. LIMITATIONS: Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis. CONCLUSIONS: Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.

Update on efficacy of the approved remdesivir regimen for treatment of COVID-19: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Efficacy of remdesivir for COVID-19 remains unclear. We updated our published systematic review to better inform on the use of remdesivir for COVID-19. METHODS: We searched for randomized controlled trials (RCTs) among hospitalized COVID-19 patients. Meta-analysis was conducted using an inverse variance, random-effects model, presenting relative risk (RR) or mean difference (MD) and their associated 95% confidence intervals (CIs). Statistical heterogeneity was calculated using the I2 statistic. In addition, we conducted trial sequential analysis (TSA). Outcomes with additional data were clinical progression, hospitalization days, and all-cause mortality. RESULTS: We included nine RCTs (12,876 individuals). Three trials each were of a low, unclear, and a high risk of bias. Compared with no treatment/placebo, remdesivir (100 mg daily, over 10 days) significantly improved clinical progression (RR 1.06, CI 1.02-1.11), but did not significantly reduce hospitalization days (MD -0.48, CI -2.18-1.21) and all-cause mortality (RR 0.92, CI 0.84-1.01). TSA suggested that further information is not required to conclude on the efficacy of remdesivir in improving clinical progression, and that, while more information is required for hospitalization days and all-cause mortality, further RCTs to prove fewer hospitalization days may be futile, as efficacy of remdesivir for this outcome is unlikely. CONCLUSIONS: Remdesivir appeared promising for COVID-19, but there is insufficient evidence of its efficacy. High quality RCTs are needed for a stronger evidence base.

Cardiorespiratory Fitness and Physical Activity in Pediatric Diabetes: A Systemic Review and Meta-Analysis.

Importance: It is unclear whether cardiorespiratory fitness (CRF) and physical activity are lower among youths with type 1 diabetes (T1D) and type 2 diabetes (T2D) compared with youths without diabetes. Objective: To describe the magnitude, precision, and constancy of the differences in CRF and physical activity among youths with and without diabetes. Data Sources: MEDLINE, Embase, CINAHL, and SPORTDiscus were searched from January 1, 2000, to May 1, 2022, for eligible studies. Study Selection: Observational studies with measures of CRF and physical activity in children and adolescents aged 18 years or younger with T1D or T2D and a control group were included. Data Extraction and Synthesis: Data extraction was completed by 2 independent reviewers. A random-effects meta-analysis model was used to estimate differences in main outcomes. The pooled effect estimate was measured as standardized mean differences (SMDs) with 95% CIs. The Preferred Reporting Items for Systematic Review and Meta-Analyses guideline was followed. Main Outcomes and Measures: The main outcomes were objectively measured CRF obtained from a graded maximal exercise test and subjective or objective measures of physical activity. Subgroup analyses were performed for weight status and measurement type for outcome measures. Results: Of 7857 unique citations retrieved, 9 studies (755 participants) with measures of CRF and 9 studies (1233 participants) with measures of physical activity for youths with T2D were included; for youths with T1D, 23 studies with measures of CRF (2082 participants) and 36 studies with measures of PA (12 196 participants) were included. Random-effects models revealed that directly measured CRF was lower in youths with T2D (SMD, -1.06; 95% CI, -1.57 to -0.56; I2 = 84%; 9 studies; 755 participants) and in youths with T1D (SMD, -0.39; 95% CI, -0.70 to -0.09; I2 = 89%; 22 studies; 2082 participants) compared with controls. Random-effects models revealed that daily physical activity was marginally lower in youths with T1D (SMD, -0.29; 95% CI, -0.46 to -0.11; I2 = 89%; 31 studies; 12 196 participants) but not different among youths with T2D (SMD, -0.56; 95% CI, -1.28 to 0.16; I2 = 91%; 9 studies; 1233 participants) compared with controls. When analyses were restricted to studies with objective measures, physical activity was significantly lower in youths with T2D (SMD, -0.71; 95% CI, -1.36 to -0.05; I2 = 23%; 3 studies; 332 participants) and T1D (SMD, -0.67; 95% CI, -1.17 to -0.17; I2 = 93%; 12 studies; 1357 participants) compared with controls. Conclusions and Relevance: These findings suggest that deficits in CRF may be larger and more consistent in youths with T2D compared with youths with T1D, suggesting an increased risk for cardiovascular disease-related morbidity in adolescents with diabetes, particularly among those with T2D. The findings reinforce calls for novel interventions to empower youths living with diabetes to engage in regular physical activity and increase their CRF.

Characterizing research partnerships in child health research: A scoping review.

Research partnerships between researchers and knowledge users (KUs) in child health are understudied. This study examined the scope of KU engagement reported in published child health research, inclusive of health research partnership approaches and KU groups. Search strategies were developed by a health research librarian. Studies had to be in English, published since 2007, and were not excluded based on design. A two-step, multiple-person hybrid screening approach was used for study inclusion. Data on study and engagement characteristics, barriers and facilitators, and effects were extracted by one reviewer, with 10% verified by a second reviewer. Three hundred fifteen articles were included, with 243 (77.1%) published between 2019 and 2021. Community-based participatory research was the most common approach used (n = 122, 38.3%). Most studies (n = 235, 74.6%) engaged multiple KU groups (range 1-11), with children/youth, healthcare professionals, and parents/families being most frequently engaged. Reporting of barriers and facilitators and effects were variable, reported in 170 (53.8%) and 197 (62.5%) studies, respectively. Publications have increased exponentially over time. There is ongoing need to optimize evaluation and reporting consistency to facilitate growth in the field. Additional studies are needed to further our understanding of research partnerships in child health.

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.

Physical Activity for Quiescent and Mildly Active Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Physical activity (PA) may benefit people with inflammatory bowel diseases (IBD) by improving immunological response, musculoskeletal function, and psychological health. Aims: We distilled available evidence on the efficacy and safety of PA to improve health-related quality of life (HRQoL) and relieve persistent symptoms of fatigue, joint pain, abdominal pain, stress, anxiety, and depression in individuals with quiescent/mild IBD. Methods: We searched for trials in eight databases and trial registries. Trials using PA as an adjunct therapy in the management of adults (≥18 years) with quiescent or mild IBD, published in English between 2011 and 2023 were identified. Summary effect estimates were expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) using random-effects model. Results: From the 10,862 citations retrieved, we included seven randomized controlled trials (RCTs) and one non-RCT. There was no evidence of benefit of PA on HRQoL (SMD 0.34, 95%CI -0.08 to 0.77; I2 57%); high heterogeneity was noted among included trials. PA was found to be efficacious in reducing anxiety (SMD -0.35, 95%CI -0.65 to -0.05; I2 0%). There was insufficient evidence to make conclusions regarding changes in fatigue, joint pain, abdominal pain, stress, and depression. All trials deemed physical activity safe. Conclusions: PA contributes to reducing anxiety in quiescent/mild IBD. There is marked heterogeneity in methodology among trials investigating PA in adults with quiescent/mild IBD. This review highlights the need for consistent definitions of PA types and intensities in this field of research.

Equity-relevant sociodemographic variable collection in emergency medicine: A systematic review, qualitative evidence synthesis, and recommendations for practice.

OBJECTIVES: The objective was to conduct a systematic review and qualitative evidence synthesis (QES) to identify best practices, benefits, harms, facilitators, and barriers to the routine collection of sociodemographic variables in emergency departments (EDs). METHODS: This work is a systematic review and QES. We conducted a comprehensive search of Medline (Ovid), CINAHL (Ebsco), Cochrane Central (OVID), EMBASE (Ovid), and the multidisciplinary Web of Science Core database using peer-reviewed search strategies, complemented by a gray literature search. We included citations containing perspectives on routine sociodemographic variable collection in EDs and recommendations on definitions or processes of collection or benefits, harms, facilitators, or barriers related to the routine collection of sociodemographic variables in EDs. We conducted this systematic review and QES adhering to the Joanna Briggs Institute guidelines. Two reviewers independently selected included studies and extracted data. We conducted a best-fit framework synthesis and paired inductive thematic analysis of the included studies. We generated recommendations based on the QES. RESULTS: We included 21 unique reports that enrolled 10,454 patients or respondents in our systematic review and QES. Publication dates of included studies ranged from 2011 to 2021. Included citations were published in Australia, Canada, and the United States. We synthesized 11 benefits, 14 potential harms, 15 barriers, and 19 facilitators and identified 14 best practice recommendations from included citations. CONCLUSIONS: Health systems should routinely collect sociodemographic variables in EDs guided by recommendations that minimize harms and maximize benefits and consider relevant barriers and facilitators. Our recommendations can serve as a guide for the equity-focused reformation of emergency medicine health information systems.

Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ). RESULTS: Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = -  2.18; 95% CI -  2.88 to -  1.49; I 2 =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = -  2.10; 95% CI -  3.09 to -  1.11; I2 = 71%; n = 8 studies) and zonisamide (MD = -  2.31; 95% CI -  3.35 to -  1.27; I2 = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results. CONCLUSIONS: Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.

Vaccine confidence among those living with allergy during the COVID pandemic (ACCORD): A scoping review.

Background: Reports of allergic reactions to coronavirus disease 2019 (COVID-19) vaccines, coupled with an "infodemic" of misinformation, carry the potential to undermine confidence in the COVID-19 vaccines. However, no attempts have been made to comprehensively synthesize the literature on how allergic disease and fear of allergic reactions to the vaccines contribute to hesitancy. Objectives: Our aim was to review the academic and gray literature on COVID-19 vaccine hesitancy and allergic reactions. Methods: We searched 4 databases (CINAHL, PsycINFO, MEDLINE, and Embase) using a search strategy developed by content and methodologic experts. No restrictions were applied regarding COVID-19 vaccine type, country of study, or patient age. Eligible articles were restricted to 10 languages. Results: Of the 1385 unique records retrieved from our search, 60 articles (4.3%) were included. Allergic reactions to the COVID-19 vaccine were rare but slightly more common in individuals with a history of allergic disease. A fifth of the studies (13 of 60 [22%]) discussed vaccine hesitancy due to possibility of an allergic reaction. Additionally, the present review identified research on details of vaccine-related anaphylaxis (eg, a mean and median [excluding clinical trial data] of 12.4 and 5 cases per million doses, respectively) and allergic reactions (eg, a mean and median [excluding clinical trial data] of 489 and 528 cases per million doses, respectively). Conclusion: COVID-19 vaccine acceptance among individuals living with allergy and among those with no history of allergic disease may be affected by fear of an allergic reaction. Despite the low incidence of allergic reactions to the COVID-19 vaccine, fear of such reactions is one of the most commonly cited concerns reported in the literature.