Effects of dietary interventions for metabolic acidosis in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND HYPOTHESIS: Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD. METHODS: Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data. RESULTS: Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies. CONCLUSION: Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required.

The association of antiplatelet agents with mortality among patients with non-COVID-19 community-acquired pneumonia: a systematic review and meta-analysis.

Background: Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non-COVID-19 CAP remains uncertain. Objectives: To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non-COVID-19 CAP. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non-COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates. Results: We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I 2  = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I 2  = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I 2  = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias. Conclusion: In hospitalized patients with non-COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.

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.

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.

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.

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.

Stress, depression, and anxiety among undergraduate nursing students in the time of a pandemic.

INTRODUCTION: Emerging literature reports on the challenges faced by nursing students internationally during the pandemic as they continue their education. The aim of this mixed methods study was to examine stress, depression, and anxiety among undergraduate nursing students at a Canadian university during the pandemic. THEORETICAL FRAMEWORKS: Stress and coping and trauma theories informed this study. METHODS: Mixed methods included an online questionnaire composed of the Depression Anxiety Stress scales (DASS), sociodemographic data, and quality of life items with open-ended questions. RESULTS: Sample included 280 participants. Mean scores for depression and stress were in the mild level, for anxiety in the moderate level; 24 , 37 and 23 % of the sample had scores of severe or extremely severe for depression, anxiety, and stress respectively. Written comments reflected the impact on participants' relationships, motivation, struggles with remote learning, perceived heavy workloads, and impact on health and self-care, while some described positive experiences, including improved study habits. DISCUSSION: Uncertainty, isolation, sudden and ongoing changes with program delivery and a variety of psychosocial losses, helped to explain the distress many shared. The disconnect between reported levels of use of mental health services and the higher levels of mental distress raises the question of access to and use of these services. IMPLICATIONS FOR AN INTERNATIONAL AUDIENCE: The importance of developing and maintaining effective coping, including a support system, and committing to healthy self-care during challenging times was reinforced. CONCLUSIONS: This difficult time for nursing students emphasized the need to ensure attention to student well-being and mental health during their foundational educational experiences.

The impact of early palliative care on the quality of life of patients with advanced pancreatic cancer: The IMPERATIVE case-crossover study.

PURPOSE: Pancreatic cancer is a lethal disease. Many patients experience a heavy burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care alongside standard oncologic care results in improved QOL and survival in some cancer types. The benefit in advanced pancreatic cancer (APC) is not fully quantified. METHODS: In this prospective case-crossover study, patients ≥ 18 years old with APC were recruited from ambulatory clinics at a tertiary cancer center. Patients underwent a palliative care consultation within 2 weeks of registration, with follow up visits every 2 weeks for the first month, then every 4 weeks until week 16, then as needed. The primary outcome was change in QOL between baseline (BL) and week 16, measured by Functional Assessment of Cancer Therapy - hepatobiliary (FACT-Hep). Secondary outcomes included symptom control (ESAS-r), depression, and anxiety (HADS, PHQ-9) at week 16. RESULTS: Of 40 patients, 25 (63%) were male, 28 (70%) had metastatic disease, 31 (78%) had ECOG performance status 0-1, 31 (78%) received chemotherapy. Median age was 70. Mean FACT-hep score at BL was 118.8, compared to 125.7 at week 16 (mean change 6.89, [95%CI (-1.69-15.6); p = 0.11]). On multivariable analysis, metastatic disease (mean change 15.3 [95%CI (5.3-25.2); p = 0.004]) and age < 70 (mean change 12.9 [95%CI (0.5-25.4); p = 0.04]) were associated with improved QOL. Patients with metastatic disease had significant improvement in symptom burden (mean change -7.4 [95%CI (-13.4 to -1.4); p = 0.02]). There was no difference in depression or anxiety from BL to week 16. CONCLUSION: Palliative care should be integrated early in the journey for patients with APC, as it can improve QOL and symptom burden. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03837132.

Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis.

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Preventing Punitive Violence: Implementing Positive Discipline in Everyday Parenting (PDEP) with Marginalized Populations in Bangladesh.

Physical and other types of punishment remain common in Bangladesh, despite overwhelming evidence of their harm and worldwide efforts to decrease their use. One of the strategic priorities of Save the Children in Bangladesh's Child Protection Program is to protect children from physical and humiliating punishment in homes, schools, and other settings. Save the Children in Bangladesh selected the Positive Discipline in Everyday Parenting (PDEP) Program to provide parents with alternatives to physical punishment that comply with human rights standards while strengthening relationships and understanding of child development. High-risk communities where children are particularly vulnerable were selected for this project. The PDEP program was delivered to 857 parents living in lower socioeconomic areas of Bangladesh, including ethnic minority groups, and parents living in urban slums of Dhaka and rural brothel areas. Due to the low levels of education of the participants (almost two-thirds of participants had not completed elementary school), simplified pre and posttests were utilized. Following program completion, parents' approval of both physical punishment and punishment in general declined; they were less likely to view typical parent-child conflicts as intentional misbehavior and were less reactive to frustration. In addition, parents indicated an increased understanding of the positive discipline and more confidence in their parenting skills. Before taking PDEP, 64% of the parents often felt like they just did not know what to do as a parent, compared to 34% following program completion. PDEP demonstrated the potential to decrease the use of physical and humiliating punishments by parents living in high-risk communities in Bangladesh.

A systematic review and meta-analysis of computed tomography in the diagnosis of pediatric foreign body aspiration.

INTRODUCTION: Rigid bronchoscopy remains the gold standard for the diagnosis of foreign body aspiration (FBA) despite high rates of negative bronchoscopies. The use of computed tomography (CT) imaging in the assessment of FBA has recently emerged and could help obviate unnecessary bronchoscopy in these patients. The aim of this study is to assess the diagnostic accuracy of CT in the diagnosis of pediatric FBA. METHODS: A systematic literature review was conducted to identify studies reporting the use of CT imaging in suspected pediatric FBA. The search included published articles in Ovid MEDLINE, Ovid EMBASE, PubMed MEDLINE and Web of Science. The search strategy included all articles from inception of the database to January 2021. Manuscripts were reviewed and graded for quality using the QUADAS-2 tool. Subgroup analyses based on the use of virtual bronchoscopy (VB) and sedation was conducted. A meta-analysis evaluating the use of VB in the diagnosis of FBA was also conducted. RESULTS: Sixteen manuscripts met all inclusion criteria. In total, 2056 pediatric patients ranging from 0.3 to 15 years underwent CT for suspected FBA. The sensitivity and specificity of CT were 98.8% and 96.6%, respectively. VB was used in 71.4% (1391/1948) of patients while sedation during CT was required in 70.2% (1263/1800) of patients. Radiation dosing ranged from 0.04 to 2 mSv, 0.99-59.1 mGy-cm and 0.03-16.99 mGy. CONCLUSION: CT can accurately diagnose pediatric FBA and can help decrease the rate of unnecessary bronchoscopies with an acceptable dose of radiation.

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.

Assessing the impact of the Royal Canadian Mounted Police (RCMP) protocol and Emotional Resilience Skills Training (ERST) among diverse public safety personnel.

BACKGROUND: Public safety personnel (PSP; e.g., border services personnel, correctional workers, firefighters, paramedics, police, public safety communicators) are frequently exposed to potentially psychologically traumatic events. Such events contribute to substantial and growing challenges from posttraumatic stress injuries (PTSIs), including but not limited to posttraumatic stress disorder. METHODS: The current protocol paper describes the PSP PTSI Study (i.e., design, measures, materials, hypotheses, planned analyses, expected implications, and limitations), which was originally designed to evaluate an evidence-informed, proactive system of mental health assessment and training among Royal Canadian Mounted Police for delivery among diverse PSP (i.e., firefighters, municipal police, paramedics, public safety communicators). Specifically, the PSP PTSI Study will: (1) adapt, implement, and assess the impact of a system for ongoing (i.e., annual, monthly, daily) evidence-based assessments; (2) evaluate associations between demographic variables and PTSI; (3) longitudinally assess individual differences associated with PTSI; and, (4) assess the impact of providing diverse PSP with a tailored version of the Emotional Resilience Skills Training originally developed for the Royal Canadian Mounted Police in mitigating PTSIs based on the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders. Participants are assessed pre- and post-training, and then at a follow-up 1-year after training. The assessments include clinical interviews, self-report surveys including brief daily and monthly assessments, and daily biometric data. The current protocol paper also describes participant recruitment and developments to date. DISCUSSION: The PSP PTSI Study is an opportunity to implement, test, and improve a set of evidence-based tools and training as part of an evidence-informed solution to protect PSP mental health. The current protocol paper provides details to inform and support translation of the PSP PTSI Study results as well as informing and supporting replication efforts by other researchers. TRIAL REGISTRATION: Hypotheses Registration: aspredicted.org, #90136. Registered 7 March 2022-Prospectively registered. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05530642. Registered 1 September 2022-Retrospectively registered. The subsequent PSP PTSI Study results are expected to benefit the mental health of all participants and, ultimately, all PSP.

Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures. METHODS: This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs. RESULTS: From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I2 15% and RR 2.79, 95% CI 1.58 to 4.93, I2 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes. CONCLUSION: This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.

Factors associated with reporting of the Prevention of Falls Network Europe (ProFaNE) core outcome set domains in randomized trials on falls in older people: a citation analysis and correlational study.

BACKGROUND: Core outcome sets are advocated as a means to standardize outcome reporting across randomized controlled trials (RCTs) and reduce selective outcome reporting. In 2005, the Prevention of Falls Network Europe (ProFaNE) published a core outcome set identifying five domains that should be measured and reported, at a minimum, in RCTs or meta-analysis on falls in older people. As reporting of all five domains of the ProFaNE core outcome set has been minimal, we set out to investigate factors associated with reporting of the ProFaNE core outcome set domains in a purposeful sample of RCTs on falls in older people. METHODS: We conducted a systematic citation analysis to identify all reports of RCTs focused on falls in older people that cited the ProFaNE core outcome set between October 2005 and July 2021. We abstracted author-level, study-level, and manuscript-level data and whether each domain of the ProFaNE core outcome set was reported. We used penalized LASSO regression to identify factors associated with the mean percentage of ProFaNE core outcome set domains reported. RESULTS: We identified 85 eligible reports of RCTs. Articles were published between 2007 and 2021, described 75 unique RCTs, and were authored by 76 unique corresponding authors. The percentage of ProFaNE core outcome set domains reported ranged from 0 to 100%, with a median of 40% and mean (standard deviation, SD) of 52.2% (25.1). RCTs funded by a non-industry source reported a higher mean percentage of domains than RCTs without a non-industry funding source (estimated mean difference = 17.5%; 95% confidence interval (CI) 1.8-33.2). RCTs examining exercise (15.4%; 95% CI 1.9-28.9) or multi-component/factorial (17.4%; 95% CI 4.7-30.1) interventions each reported a higher mean percentage of domains than RCTs examining other intervention types. CONCLUSIONS: We found that RCTs funded by at least one non-industry source, examining exercise or multi-component/factorial interventions, reported the highest percentages of ProFaNE core outcome set domains. Findings may help inform strategies to increase the impact of the ProFaNE core outcome set. Ultimately, this may lead to enhanced knowledge of the effectiveness and safety of interventions to prevent and/or manage falls in older people.

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.

Impact of employing primary healthcare professionals in emergency department triage on patient flow outcomes: a systematic review and meta-analysis.

OBJECTIVES: To identify, critically appraise and summarise evidence on the impact of employing primary healthcare professionals (PHCPs: family physicians/general practitioners (GPs), nurse practitioners (NP) and nurses with increased authority) in the emergency department (ED) triage, on patient flow outcomes. METHODS: We searched Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley) and CINAHL (EBSCO) (inception to January 2020). Our primary outcome was the time to provider initial assessment (PIA). Secondary outcomes included time to triage, proportion of patients leaving without being seen (LWBS), length of stay (ED LOS), proportion of patients leaving against medical advice (LAMA), number of repeat ED visits and patient satisfaction. Two independent reviewers selected studies, extracted data and assessed study quality using the National Institute for Health and Care Excellence quality assessment tool. RESULTS: From 23 973 records, 40 comparative studies including 10 randomised controlled trials (RCTs) and 13 pre-post studies were included. PHCP interventions were led by NP (n=14), GP (n=3) or nurses with increased authority (n=23) at triage. In all studies, PHCP-led intervention effectiveness was compared with the traditional nurse-led triage model. Median duration of the interventions was 6 months. Study quality was generally low (confounding bias); 7 RCTs were classified as moderate quality. Most studies reported that PHCP-led triage interventions decreased the PIA (13/14), ED LOS (29/30), proportion of patients LWBS (8/10), time to triage (3/3) and repeat ED visits (5/6), and increased the patient satisfaction (8/10). The proportion of patients LAMA did not differ between groups (3/3). Evidence from RCTs (n=8) as well as other study designs showed a significant decrease in ED LOS favouring the PHCP-led interventions. CONCLUSIONS: Overall, PHCP-led triage interventions improved ED patient flow metrics. There was a significant decrease in ED LOS irrespective of the study design, favouring the PHCP-led interventions. Evidence from well-designed high-quality RCTs is required prior to widespread implementation. PROSPERO REGISTRATION NUMBER: CRD42020148053.

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.

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.