Practice variation in urine collection methods among pre-toilet trained children with suspected urinary tract infection: a systematic review.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of acute illness among infants and young children. There are numerous methods for collecting urine in children who are not toilet trained. This review examined practice variation in the urine collection methods for diagnosing UTI in non-toilet-trained children. METHODS: A systematic review was completed by searching MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), and JBI (Ovid) from January 1, 2000 until October 9, 2021 and updated on May 24, 2023. Studies were included if they were conducted in an acute care facility, examined pre-toilet trained children, and compared one urine collection method with another for relevant health care outcomes (such as length of stay in an ED, or re-visits or readmissions to the ED) or provider satisfaction. Two independent reviewers screened the identified articles independently, and those included in the final analysis were assessed for quality and bias using the Newcastle-Ottawa Scale. RESULTS: Overall, 2535 articles were reviewed and 8 studies with a total of 728 children were included in the final analysis. Seven studies investigated the primary outcome of interest, practice variation in urine collection methods to diagnose a UTI. The seven studies that investigated novel methods of urine collection concluded that there were improved health care outcomes compared to conventional methods. Novel methods include emerging methods that are not captured yet captured in clinical practice guidelines including the use of ultrasound guidance to aid existing techniques. Three studies which investigated healthcare provider satisfaction found preference to novel methods of urine collection. CONCLUSIONS: There is significant practice variation in the urine collection methods within and between countries. Further research is needed to better examine practice variation among clinicians and adherence to national organizations and societies guidelines. PROSPERO registration number CRD42021267754.

Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer. METHODS: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid-related adverse events were also summarized. RESULTS: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open-label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy-induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis-related adverse events were reported. CONCLUSIONS: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. OBJECTIVES: To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. SEARCH METHODS: We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events). DATA COLLECTION AND ANALYSIS: Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.  Any glucocorticoid compared to placebo  Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence).  One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).  Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.  There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review. AUTHORS' CONCLUSIONS: The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.

Training interventions to improve adenoma detection rates during colonoscopy: a systematic review and meta-analysis.

BACKGROUND: Colonoscopies are effective means of detecting and removing precancerous adenomatous polyps. The adenoma detection rate (ADR) is a marker of colonoscopy quality and an independent predictor of colorectal cancer incidence. Focused training interventions may improve an endoscopist's ADR, but the supporting research is limited. This systematic review and meta-analysis identified, critically appraised, and meta-analyzed data from randomized trials (RCTs) evaluating the effect of training interventions on ADRs. METHODS: Ovid Medline, EMBASE, CENTRAL, Eric, CINAHL, Scopus, Web of Science, and ClinicalTrials.gov were searched for RCTs investigating the effect of an educational intervention on ADRs. Two reviewers independently screened, identified, and extracted trial-level data. Internal validity was assessed in duplicate using the Risk of Bias tool. Our primary outcome was the ADR. Secondary outcomes were advanced ADR, adenocarcinoma detection rate, polyp detection rate, and withdrawal times. Safety outcomes were post-polypectomy bleeding rate and colonoscopy-related perforation rate. RESULTS: From 2837 screened citations, we identified 3 trials (119 endoscopists) meeting our inclusion criteria. Training interventions were associated with a trend toward increased ADRs (odds ratio 1.16, 95% confidence interval (CI) 1.00-1.34; I2 83%; 3 trials; 119 endoscopists). When limited to screening colonoscopies, the odds ratio for ADRs associated with training interventions was 1.17 (95% CI 1.00-1.36; I2 80%; 3 trials; 119 endoscopists). There was a high level of heterogeneity between the trials' training interventions. Training intervention improved the advanced ADR, adenocarcinoma detection rate, polyp detection rate, and withdrawal times. Safety outcomes were not reported. CONCLUSIONS: A focused training intervention was associated with a strong trend toward increased ADRs among certified endoscopists. While the described training interventions definitely show promise, further efforts around continuing professional developments activities are needed to more consistently improve ADRS among certified endoscopists.

Dexmedetomidine versus propofol sedation in reducing delirium among older adults in the ICU: A systematic review and meta-analysis.

BACKGROUND: Delirium is common in the ICU, with incidence rates reported to be upwards of 70%. Due to the significant morbidity and mortality associated with delirium, it is hypothesised that a delirium-free sedative agent will improve outcomes in older adults admitted to the ICU. OBJECTIVES: To assess if dexmedetomidine sedation is associated with a reduction in ICU delirium among older adults, and to evaluate its risks and benefits compared with propofol sedation. DESIGN: Systematic review of randomised controlled trials and cohort studies with meta-analyses. DATA SOURCES: Articles published from database inception to 8 April 2019 were retrieved from Medline, EMBASE, Evidence-based Medicine Reviews, International Pharmaceutical Abstracts, Scopus, ClinicalTrials.gov and WHO Trials. ELIGIBILITY: Studies were included if they compared dexmedetomidine sedation with propofol in the ICU, reported the incidence of delirium as an outcome and had a mean/median sample age of at least 60. Studies that examined dexmedetomidine and propofol use intra-operatively or as part of general anaesthesia were excluded. RESULTS: Dexmedetomidine sedation was associated with a lower incidence of delirium when compared with propofol: seven studies, n=1249; risk ratio 0.70; 95% confidence interval (CI) 0.52 to 0.95; P = 0.02. There was no statistically significant difference in the incidence of bradycardia: three studies, n=278; risk ratio 1.52; 95% CI 0.85 to 2.72; P = 0.16, and hypotension: six studies, n=867 patients; risk ratio 1.12; 95% CI 0.86 to 1.45; P = 0.42. Dexmedetomidine sedation did not reduce hospital length of stay, ICU length of stay or duration of mechanical ventilation compared with propofol. CONCLUSION: Compared with propofol, dexmedetomidine sedation in the ICU is associated with lower delirium incidence among older adults with no significant increase in adverse events. In older adult ICU patients at risk of developing delirium, sedation with dexmedetomidine should be considered. Further research is warranted to elucidate and explain the mechanisms underlying this process, and to confirm our findings with large, multicentre trials. TRIAL REGISTRATION: The study protocol has been registered in PROSPERO (CRD42018099339).

A failed attempt at developing a search filter for systematic review methodology articles in Ovid Embase.

OBJECTIVES: This paper describes the development, execution, and subsequent failure of an attempt to create an Ovid Embase search filter for locating systematic review methodology articles. METHODS: The authors devised a work plan, based on best practices, for search filter development that has been outlined in the literature. Three reference samples were gathered by identifying the OVID Embase records for specific articles that were included in the PubMed Systematic Review Methods subset. The first sample was analyzed to develop a set of keywords and subject headings to include in the search filter. The second and third samples would have been used to calibrate the search filter and to calculate filter sensitivity and precision, respectively. RESULTS: Technical shortcomings, database indexing practices, and the fuzzy nature of keyword terminology relevant to the topic prevented us from designing the search filter. CONCLUSION: Creating a search filter to identify systematic review methodology articles in Ovid Embase is not possible at this time.

An output evaluation of a health research foundation's enhanced grant review process for new investigators.

BACKGROUND: We assessed the ability of the Manitoba Medical Service Foundation (MMSF, a small not-for-profit foundation affiliated with Manitoba Blue Cross) to determine the best candidates for selection to receive research funding support among new researchers applying to the Research Operating Grants Programme (ROGP). METHODS: Using bibliometric and grants funding analyses, we retrospectively compared indices of academic outputs from five cohorts of MMSF-funded and not MMSF-funded applicants to the annual MMSF ROGP over 2008 to 2012, from 1 to 5 years after having received evaluation decisions from the MMSF enhanced grant review process. RESULTS: Those researchers funded by the MMSF competition (MMSF-funded) had a statistically significant greater number of publications, a higher h-index and greater national Tri-Council (TC) funding, versus those not selected for funding (not MMSF-funded). MMSF-funded applicants and the Manitoba research community have created a strong and rapid (within 1 to 5 years of receiving the MMSF grant) local economic return on investment associated with the MMSF ROGP that supports new investigators, of approximately nine-fold for TC grants by the principal investigator, and of 34-fold for the principal investigator on collaborative (total) TC grants. CONCLUSIONS: The use of small amounts of seed money for competitive research grants at early stages of an MMSF-funded applicant's career correlates with future short-term success of that applicant. The ability to correctly select promising candidates who subsequently demonstrate greater academic performance after the MMSF funding shows the selection process and the ROGP to be of merit. Multiple components may have contributed to this outcome, including a direct presentation and interview process of the candidate with five-person selection subcommittees, plus an assessment by an external reviewer (the enhanced grant review process). The selection methods used here may add value to the research grant selection processes of new researchers.

Analysis of a librarian-mediated literature search service.

Librarian-mediated literature searching is a key service provided at medical libraries. This analysis outlines ten years of data on 19,248 literature searches and describes information on the volume and frequency of search requests, time spent per search, databases used, and professional designations of the patron requestors. Combined with information on best practices for expert searching and evaluations of similar services, these findings were used to form recommendations on the improvement and standardization of a literature search service at a large health library system.

Information needs of public health students.

BACKGROUND: The number of public health degrees and programmes is growing rapidly. This means that a diverse and multidisciplinary group of students are in need of expert library services to navigate the complicated world of public health information. OBJECTIVE: To better understand the information needs of public health students, a group that has not previously been studied in the information needs literature. METHODS: An online survey. RESULTS: Of the 153 students, 38 responded (25% response rate). Their responses indicated a strong need for more tailored library instruction sessions at the point of need as opposed to general stand-alone sessions offered at the beginning of a term. It was also found that many students were unaware of public health specific resources available that could greatly aid them in their information needs. Suggestions were made on how to improve the library subject guide, specifically in the areas of more instructions related to locating hard to find resources (e.g. statistics, grey literature), and direct linking to resources (e.g. databases and relevant articles). CONCLUSION: The information needs of public health students are diverse and complex. It is imperative that the library has a solid understanding of their needs and is able to offer them targeted and relevant library services.

Prescribing and deprescribing guidance for benzodiazepine and benzodiazepine receptor agonist use in adults with depression, anxiety, and insomnia: an international scoping review.

Background: Clinical practice guidelines and guidance documents routinely offer prescribing clinicians' recommendations and instruction on the use of psychotropic drugs for mental illness. We sought to characterise parameters relevant to prescribing and deprescribing of benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA), in clinical practice guidelines and guidance documents internationally, for adult patients with unipolar depression, anxiety disorders and insomnia to understand similarities and discrepancies between evidence-based expert opinion. Methods: A Scoping Review was conducted to characterize documents that offered evidence-based and/or consensus pharmacologic guidance on the management of unipolar depression, anxiety disorders, obsessive-compulsive disorders, post-traumatic stress disorders and insomnia. A systematic search was conducted of PubMed, SCOPUS, PsycINFO and CINAHL from inception to October 13, 2023 and supplemented by a gray literature search. Documents were screened in Covidence for eligibility. Subsequent data-charting on eligible documents collected information on aspects of both prescribing and deprescribing. Findings: 113 documents offering guidance on BZD/BZRA use were data-charted. Overall, documents gathered were from Asia (n = 11), Europe (n = 34), North America (n = 37), Oceania (n = 7), and South America (n = 4) with the remainder being "International" (n = 20) and not representative to any particular region or country. By condition the documents reviewed covered unipolar depressive disorders (n = 28), anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder (n = 42) and Insomnia (n = 25). Few documents (n = 18) were sufficiently specific and complete to consider as de-prescribing focused documents. Interpretation: Documents were in concordance in terms of BZD and BZRA not being used routinely as first-line pharmacologic agents. When used, it is advisable to restrict their duration to "short-term" use with the most commonly recommended duration being less than four weeks. Documents were less consistent in terms of prescriptive recommendations for specific drug, dosing and administration pattern (i.e regular or 'as needed') selection for each condition. Deprescribing documents were unanimously in favor of gradual dose reduction and patient shared decision-making. However, approaches towards dose-tapering differed substantially. Finally, there were inconsistencies and/or insufficiency of detail, among deprescribing documents, in terms of switching to a long-acting BZD, use of adjunctive pharmacotherapies and micro-tapering. Funding: The authors received no funding for this work.

Considering Sex and Gender in Therapeutics throughout the Product Life Cycle: A Narrative Review and Case Study of Gilteritinib.

Background: Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects, which may in turn have clinical consequences for patients' lives. Nonetheless, sex-related factors are not always taken into account in clinical trial design or clinical decision-making, for multiple reasons, including a paucity of studies that clearly and objectively study and measure sex-disaggregated and sex-related outcomes, as well as gaps in regulatory and policy structures for integrating these considerations. Objectives: To complete a narrative review and use a case study to understand available evidence, inform future research, and provide policy considerations that incorporate information on sex- and gender-related factors into clinician-facing resources. Methods: A comprehensive review of available literature was conducted using a sex- and gender-based analysis plus (SGBA Plus) approach to identify sex- and/or gender-disaggregated information for gilteritinib, a chemotherapeutic agent. Systematic searches were performed in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus, and ClinicalTrials.gov, from inception to March 18, 2021. The information was then summarized and compared with the Canadian product monograph for this drug. Results: Of 311 records screened, 3 provided SGBA Plus information as a component of outcomes, rather than just as categories or demographic characteristics. Of these, 2 were case studies, and 1 was a clinical trial. No studies from the ClinicalTrials.gov database that were in progress at the time of this review provided details about sex-disaggregated outcomes. The Canadian product monograph did not include sex-disaggregated outcome data. Conclusions: The available evidence from clinical trials, other published literature, and guidance documents does not provide details about sex-disaggregated outcomes for gilteritinib. This paucity of available evidence may create a challenge for clinicians who are making decisions about the efficacy and safety of prescribed therapies in sex-specific populations that have not been well studied.

Contexte: Les facteurs liés au sexe biologique influencent les processus pharmacocinétiques, pharmacodynamiques et pathologiques, qui peuvent avoir une incidence sur la prévisibilité du dosage des médicaments et des effets indésirables. Ceci peut à son tour avoir des conséquences cliniques sur la vie des patients. Néanmoins, les facteurs liés au sexe ne sont pas toujours pris en compte dans la conception des essais cliniques ou la prise de décision clinique, et cela pour de nombreuses raisons ­ notamment le manque d'études qui examinent et mesurent clairement et objectivement les résultats ventilés par sexe et liés au sexe ainsi que les lacunes dans les réglementations et structures politiques pour intégrer ces considérations. Objectifs: Mener un examen narratif et utiliser une étude de cas pour comprendre les preuves disponibles, éclairer les recherches futures et fournir des considérations politiques qui intègrent des informations sur les facteurs liés au sexe et au genre dans les ressources destinées aux cliniciens. Méthodes: Une revue complète de la littérature disponible a été réalisée à l'aide d'une analyse comparative fondée sur le sexe et le genre Plus (ACSG Plus) pour identifier les informations ventilées par sexe et/ou par genre pour le giltéritinib, un agent chimiothérapeutique. Des recherches systématiques ont été effectuées dans MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus et ClinicalTrials.gov, depuis la création de chaque base de données jusqu'au 18 mars 2021. Ces informations ont ensuite été résumées et comparées avec la monographie canadienne de produit pharmaceutique pour ce médicament. Résultats: Sur les 311 documents examinés, 3 ont fourni des informations ACSG Plus en tant que composante des résultats, plutôt que simplement en tant que catégories ou caractéristiques démographiques. Parmi ceux-ci, 2 étaient des études de cas et 1 était un essai clinique. Aucune étude de la base de données ClinicalTrials.gov en cours au moment de cette revue n'a fourni de détails sur les résultats ventilés par sexe. La monographie de produit canadienne ne comprenait pas de données sur les résultats ventilées par sexe. Conclusions: Les preuves disponibles issues d'essais cliniques, d'autres publications et de documents d'orientation ne fournissent pas de détails sur les résultats ventilés par sexe pour le giltéritinib. Ce manque d'éléments probants disponibles peut constituer un défi pour les cliniciens qui prennent des décisions sur l'efficacité et l'innocuité des thérapies prescrites chez des populations sexospécifiques qui n'ont pas été bien étudiées.

Sex, Gender, and the Regulation of Prescription Drugs: Omissions and Opportunities.

The regulation of prescription drugs is an important health, safety, and equity issue. However, regulatory processes do not always consider evidence on sex, gender, and factors such as age and race, omissions that advocates have highlighted for several decades. Assessing the impact of sex-related factors is critical to ensuring drug safety and efficacy for females and males, and for informing clinical product monographs and consumer information. Gender-related factors affect prescribing, access to drugs, needs and desires for specific prescribed therapies. This article draws on a policy-research partnership project that examined the lifecycle management of prescription drugs in Canada using a sex and gender-based analysis plus (SGBA+) lens. In the same time period, Health Canada created a Scientific Advisory Committee on Health Products for Women, in part to examine drug regulation. We report on grey literature and selected regulatory documents to illustrate the extent to which sex and gender-based analysis plus (SGBA+) is utilized in regulation and policy. We identify omissions in the management of prescription drugs, and name opportunities for improvements by integrating SGBA+ into drug sponsor applications, clinical trials development, and pharmacovigilance. We report on recent efforts to incorporate sex disaggregated data and recommend ways that the management of prescription drugs can benefit from more integration of sex, gender, and equity.

Readiness of emergency departments for pediatric patients and pediatric mortality: a systematic review.

BACKGROUND: Most children who need emergency care visit general emergency departments and urgent care centres; the weighted pediatric readiness score (WPRS) is currently used to evaluate emergency departments' readiness for pediatric patients. The aim of this study was to determine whether a higher WPRS was associated with decreased mortality and improved health care outcomes and utilization. METHODS: We conducted a systematic review of cohort and cross-sectional studies on emergency departments that care for children (age ≤ 21 yr). We searched MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), CINAHL (EBSCO), Global Health (Ovid) and Scopus from inception until July 29, 2022. Articles identified were screened for inclusion by 2 independent reviewers. The primary outcome was mortality, and the secondary outcomes were health care outcomes and utilization. We used the Newcastle-Ottawa Scale to assess for quality and bias of the included studies. The I 2 statistic was calculated to quantify study heterogeneity. RESULTS: We identified 1789 articles. Eight articles were included in the final analysis. Three studies showed an inverse association between highest WPRS quartile and pediatric mortality (pooled odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26 to 0.78; I 2 = 89%, low certainty of evidence) in random-effects meta-analysis. Likewise, 1 study not included in the meta-analysis also reported an inverse association with a 1-point increase in WPRS (OR 0.93, 95% CI 0.88 to 0.98). One study reported that the highest WPRS quartile was associated with shorter length of stay in hospital (ß -0.36 days, 95% CI -0.61 to -0.10). Three studies concluded that the highest WPRS quartile was associated with fewer interfacility transfers. The certainty of evidence is low for mortality and moderate for the studied health care outcomes and utilization. INTERPRETATION: The data suggest a potential inverse association between the WPRS of emergency departments and mortality risk in children. More studies are needed to refute or confirm these findings. PROTOCOL REGISTRATION: PROSPERO-CRD42020191149.

A Sex- and Gender-Based Analysis of Adverse Drug Reactions: A Scoping Review of Pharmacovigilance Databases.

Drug-related adverse events or adverse drug reactions (ADRs) are currently partially or substantially under-reported. ADR reporting systems need to expand their focus to include sex- and gender-related factors in order to understand, prevent, or reduce the occurrence of ADRs in all people, particularly women. This scoping review describes adverse drug reactions reported to international pharmacovigilance databases. It identifies the drug classes most commonly associated with ADRs and synthesizes the evidence on ADRs utilizing a sex- and gender-based analysis plus (SGBA+) to assess the differential outcomes reported in the individual studies. We developed a systematic search strategy and applied it to six electronic databases, ultimately including 35 papers. Overall, the evidence shows that women are involved in more ADR reports than men across different countries, although in some cases, men experience more serious ADRs. Most studies were conducted in higher-income countries; the terms adverse drug reactions and adverse drug events are used interchangeably, and there is a lack of standardization between systems. Additional research is needed to identify the relationships between sex- and gender-related factors in the occurrence and reporting of ADRs to adequately detect and prevent ADRs, as well as to tailor and prepare effective reporting for the lifecycle management of drugs.

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.

Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) after cardiac surgery is associated with longer hospital stay and increased in-hospital death and stroke, but its long-term implications remain incompletely understood. A systematic literature review was undertaken to investigate the impact of POAF on long-term death and stroke in adult patients who undergo cardiac operations. METHODS: Electronic databases (Cochrane, Embase, Ovid MEDLINE, and PubMed) were queried from inception to October 2018. Included studies compared long-term outcomes after cardiac operations in patients with and without POAF. Adjusted and unadjusted meta-analyses examined death, stroke, and major adverse cardiac and cerebrovascular events. Risk of bias was evaluated with the Newcastle-Ottawa Scale. RESULTS: The inclusion criteria were met by 32 studies describing 155,575 patients who had undergone cardiac operations. POAF occurred in 36,988 patients (23.7%). Meta-analysis of 10 studies (44,367 patients) demonstrated increased 1-year death in patients with POAF (odds ratio, 2.60; 95% confidence interval, 2-3.38; P < .01). Aggregate adjusted hazard of death (16 studies, n = 84,295) was also increased in patients with POAF (hazard ratio, 1.25; 95% confidence interval, 1.2-1.3; P < .01). CONCLUSIONS: This systematic review and meta-analysis identified an association between POAF and long-term death after cardiac surgery. More comprehensive POAF prevention and management, including more stringent follow-up for POAF recurrence after hospital discharge, may be indicated. The included studies used inconsistent definitions of POAF and variable exclusion criteria; however, estimates of heterogeneity are low. Differences in preoperative comorbidities, such as age, ejection fraction, and obesity, may not be fully accounted for in adjusted analyses. Future work is required to delineate mechanisms linking POAF and death in this population.

Disease-Associated Costs in Children With Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: As a chronic noncurable disorder often diagnosed in childhood or adolescence, inflammatory bowel disease (IBD) confers a significant financial lifetime burden. The objective of this systematic review was to determine the disease-associated costs (both direct and indirect) associated with IBD in children and young adults. METHODS: We conducted a systematic review of the literature and included any study reporting direct health services-related costs or the indirect economic burden of IBD in persons aged ≤19 years (PROSPERO protocol number CRD2016036128). A technical panel of experts in pediatric gastroenterology and research methodology formulated the review questions, reviewed the search strategies and review methods, and provided input throughout the review process. RESULTS: Nine studies met criteria for inclusion, 6 of which examined direct costs, 1 of which examined both direct and indirect costs, 1 of which assessed indirect costs, and 1 of which assessed out-of-pocket (OOP) costs. Inflammatory bowel disease-associated costs were significantly higher compared with costs in non-IBD populations, with wide variations in cost estimates, which prevented us from conducting a meta-analysis. Costs in Crohn's disease were higher than in ulcerative colitis. Overall, direct costs shifted from inpatient hospitalization as a major source of direct costs to medications, mainly driven by anti-tumor necrosis factor agents, as the leading cause of direct costs. Predictors of high costs included uncontrolled disease, corticosteroid treatment in the previous year, and comorbidity burden. CONCLUSIONS: The pediatric literature examining IBD-attributable costs is limited, with widely variable cost estimates. There is a significant knowledge gap in the research surrounding indirect costs and OOP expenses.

Medication review service implementation in community pharmacy settings: Scoping review with focus on implementation studies.

BACKGROUND: Medication reviews are a structured clinical intervention with the general goals of improving patient drug knowledge and detecting and resolving drug-related problems in an individual patient's medication regimen. A variety of barriers entrenched in the traditional drug distribution and dispensing model of pharmacy business has continued to challenge the implementation efforts of medication review services worldwide in the community pharmacy setting. MAIN OBJECTIVES: i) Characterize original research studies that sought to enhance medication review service implementation in community pharmacy settings. ii) Categorize the broader corpus of scientific literature (beyond original implementation studies) on medication review service implementation in community pharmacy settings. METHODS: A broad systematic search strategy was applied to ovid MEDLINE, Embase, CINAHL and Cochrane Library to create an over-arching view and extensively ordered bibliography of the diverse research publication types dealing with the topic of medication review service implementation in the community pharmacy setting. A scoping review was subsequently conducted on original research studies that utilized various strategies to enhance the implementation of this service in community pharmacies. Data-charting evaluated the location of implementation studies, the strategies undertaken, the scale of implementation strategies, the use of DII (Dissemination, Implementation and Improvement) science theory, sample sizes, and DII outcomes. RESULTS: Of 5947 records screened, 419 fulfilled the inclusion criteria (from abstract screening) to be deemed suitable for categorization and inclusion into the broader survey on this topic. Of these 419 publications, only 75 were original research specifically focused on enhancing the implementation of medication reviews in community pharmacy. A large majority of the publications were qualitative studies (n = 203). The remaining articles were improvement studies (n = 36), descriptive observational studies (n = 49), reviews (n = 69) and methodology papers (n = 16). Twenty-nine of these articles were deemed suitable for inclusion in more than one category. After full-text screening, 41 of the 75 implementation publications, representing 40 original studies, published between 1999 and 2019, were eligible for data-charting. The majority of these studies occurred in North America (n = 30), used some form of education as the most common implementation strategy (n = 22) and measured 'adoption' (extent or frequency of medication reviews delivered) most frequently as an implementation outcome (n = 30). Just over half of the studies used a multi-faceted implementation strategy (n = 21). Only 9 studies used a theory, model or framework at any point in the research process to test hypotheses or explain empirical findings. CONCLUSIONS: There is an abundance of publications addressing various issues surrounding medication review implementation in community pharmacies. However, the literature appears disproportionately represented by qualitative studies. There is also a need for more rigorously conducted implementation studies on medication review services in community pharmacy.

Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Systemic corticosteroids as the frontline treatment of respiratory distress syndrome (RDS) in preterm infants are associated with adverse effects on growth and neurodevelopmental outcome, but the pulmonary administration of steroids may help prevent the development of bronchopulmonary dysplasia (BPD) without these side effects. OBJECTIVES: To evaluate the efficacy and safety of pulmonary application of corticosteroids in preterm infants with RDS. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the WHO's International Clinical Trials Registry and grey literature were searched with no restriction on date and language of publication from inception to May 2016. Using a random-effect model, we pooled data from randomised controlled trials (RCTs) comparing inhaled or endotracheal corticosteroids with the standard of care, placebo or no other intervention in preterm infants with RDS. RESULTS: We identified 873 potential citations and included 12 unique RCTs. Pulmonary corticosteroid therapy was associated with a significant reduction in the composite outcome of BPD or death (relative risk (RR) 0.85, 95% CI 0.76 to 0.96). Pulmonary application of corticosteroids significantly reduced the incidence of patent ductus arteriosus (PDA) (RR 0.82, 95% CI 0.74 to 0.92) and pneumonia (RR 0.57, 95% CI 0.35 to 0.92). There was no evidence of a significant difference regarding the risk of neurodevelopmental impairment or other side effects. CONCLUSIONS: Pulmonary administration of corticosteroids reduces the incidence of BPD or death, pneumonia, PDA without causing any major side effects in preterm infants with RDS.