Effectiveness and Safety of Measures to Prevent Infections and Other Complications Associated With Peripheral Intravenous Catheters: A Systematic Review and Meta-analysis.

BACKGROUND: Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL, and reference lists for controlled studies from 1 January 1980-16 March 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with 3 or more trials, we conducted Bayesian random-effects meta-analyses. RESULTS: 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for 8 research questions. Based on findings of low to high COE, wearing gloves reduced the risk of overall adverse events related to insertion compared with no gloves (1 non-randomized controlled trial [non-RCT]; adjusted risk ratio [RR], .52; 95% CI, .33-.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR, 0.74, 95% credible interval, .49-1.01) compared with clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared with non-chlorhexidine-containing disinfection (1 RCT; 0.14 vs 0.68; P = .003). No statistically significant differences were found for other measures. CONCLUSIONS: Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications. CLINICAL TRIALS REGISTRATION: The protocol was registered in the Open Science Framework (https://osf.io/exdb4).

Expression of Tissue Factor and Platelet/Leukocyte Markers on Extracellular Vesicles Reflect Platelet-Leukocyte Interaction in Severe COVID-19.

Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP), and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples was associated with CRP, HMGB-1, PF4, and TF as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41+ EVs displayed the leukocyte marker CD45, and 55.5% of all EV aggregates (CD41+CD45+) co-expressed TF, which reflects the interaction of platelets and leukocytes in COVID-19 on an EV level.

Full publication of preprint articles in prevention research: an analysis of publication proportions and results consistency.

There is concern that preprint articles will lead to an increase in the amount of scientifically invalid work available. The objectives of this study were to determine the proportion of prevention preprints published within 12 months, the consistency of the effect estimates and conclusions between preprint and published articles, and the reasons for the nonpublication of preprints. Of the 329 prevention preprints that met our eligibility criteria, almost half (48.9%) were published in a peer-reviewed journal within 12 months of being posted. While 16.8% published preprints showed some change in the magnitude of the primary outcome effect estimate, 4.4% were classified as having a major change. The style or wording of the conclusion changed in 42.2%, the content in 3.1%. Preprints on chemoprevention, with a cross-sectional design, and with public and noncommercial funding had the highest probabilities of publication. The main reasons for the nonpublication of preprints were journal rejection or lack of time. The reliability of preprint articles for evidence-based decision-making is questionable. Less than half of the preprint articles on prevention research are published in a peer-reviewed journal within 12 months, and significant changes in effect sizes and/or conclusions are still possible during the peer-review process.

Evaluation of the interim Cochrane rapid review methods guidance-A mixed-methods study on the understanding of and adherence to the guidance.

The Cochrane Rapid Review Methods Group (RRMG) first released interim guidance in March 2020 to support authors in conducting rapid reviews (RRs). The objective of this mixed-methods study was to assess the adherence and investigate authors' understanding of the RRMG guidance. We identified all documents citing the Interim Cochrane RRMG guidance up to February 17, 2022 and performed an exploratory adherence analysis. We interviewed 20 RR authors to assess the recommendations' comprehensibility and reasons for any deviations. Further, we surveyed nine authors of COVID-19-related Cochrane reviews for their reasons for not conducting a RR. We analyzed 128 RRs (111 non-Cochrane, 17 Cochrane) that cited the RRMG guidance. Several recommendations were not followed by a large proportion of RR authors such as stepwise approach to study design inclusion or peer review of search strategies, whereas others were exceeded, for example, dual independent screening of abstracts/full texts. The most reported reasons for deviating from the guidance were time constraints, unclarities in the recommended approach, or inapplicability to the specific RR. Overall, the guidance was viewed as user-friendly; however, without pre-existing knowledge of systematic review (SR) conduct, the application was perceived as difficult. The main reasons for conducting a full SR over a RR were late availability of the guidance, preset mandate to conduct a SR, uncertainty regarding methodological distinctions between SR and RR, and inapplicability to the evidence base. Clarifications are warranted throughout the Interim Cochrane RRMG guidance to ensure that users with various experience levels can understand and apply its recommendations accordingly.

Beyond statistical significance: nuanced interpretations of statistically nonsignificant results were rare in Cochrane reviews - a metaepidemiological study.

OBJECTIVES: To assess the language used by systematic review authors to emphasize that statistically nonsignificant results show meaningful differences. To determine whether the magnitude of these treatment effects was distinct from nonsignificant results that authors interpreted as not different. STUDY DESIGN AND SETTING: We screened Cochrane reviews published between 2017 and 2022 for statistically nonsignificant effect estimates that authors presented as meaningful differences. We classified interpretations qualitatively and assessed them quantitatively by calculating the areas under the curve of the portions of confidence intervals exceeding the null or a minimal important difference, indicating one intervention's greater effect. RESULTS: In 2,337 reviews, we detected 139 cases where authors emphasized meaningful differences in nonsignificant results. Authors commonly used qualifying words to express uncertainty (66.9%). Sometimes (26.6%), they made absolute claims about one intervention's greater benefit or harm without acknowledging statistical uncertainty. The areas under the curve analyses indicated that some authors may overstate the importance of nonsignificant differences, whereas others may overlook meaningful differences in nonsignificant effect estimates. CONCLUSION: Nuanced interpretations of statistically nonsignificant results were rare in Cochrane reviews. Our study highlights the need for a more nuanced approach by systematic review authors when interpreting statistically nonsignificant effect estimates.

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients.

Immunothrombosis, an excessive inflammatory response with simultaneous overactivation of the coagulation system, is a central pathomechanism in sepsis and COVID-19. It is associated with cellular activation, vascular damage, and microvascular thrombosis, which can lead to multiple organ failure and death. Here, we characterized factors related to immunothrombosis in plasma samples from 78 sepsis patients. In the course of routine clinical testing, SARS-CoV-2 was detected in 14 of these patients. Viral infection was associated with a higher mortality. Both, COVID-19 negative and COVID-19 positive sepsis patients showed increased levels of effectors of immunothrombosis, including platelet factor 4, D-dimer, nucleosomes, citrullinated histone H3, high mobility group box-1 protein, as well as phosphatidylserine-expressing platelet-derived extracellular vesicles, compared to healthy controls (n = 25). Using a 27-plex cytokine bead array, we found that Interleukin (IL)-1ra, IL-6, IL-8, IL-13, tumor necrosis factor (TNF)-α, interferon inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and granulocyte-colony stimulating factor (G-CSF) were elevated in both, COVID-19 negative and COVID-19 positive sepsis patients, as compared to healthy controls. SARS-CoV-2 infection was associated with elevated levels of IP-10, MCP-1, and IL-13, while all other mediators widely overlapped between COVID-19 negative and COVID-19 positive patients.

The effectiveness of interventions to prevent loneliness and social isolation in the community-dwelling and old population: an overview of systematic reviews and meta-analysis.

BACKGROUND: Loneliness and social isolation have comparable health effects to widely acknowledged and established risk factors. Although old people are particularly affected, the effectiveness of interventions to prevent and/or mitigate social isolation and loneliness in the community-dwelling older adults is unclear. The aim of this review of reviews was to pool the findings of systematic reviews (SRs) addressing the question of effectiveness. METHODS: Ovid MEDLINE®, Health Evidence, Epistemonikos and Global Health (EBSCO) were searched from January 2017 to November 2021. Two reviewers independently assessed each SR in two consecutive steps based on previously defined eligibility criteria and appraised the methodological quality using a measurement tool to assess SRs 2, AMSTAR 2. One author extracted data from both SRs and eligible studies; another checked this. We conducted meta-analyses to pool the study results. We report the results of the random-effects and common-effect models. RESULTS: We identified five SRs containing a total of 30 eligible studies, 16 with a low or moderate risk of bias. Our random-effects meta-analysis indicates an overall SMD effect of 0.63 [95% confidence interval (CI): -0.10 to 1.36] for loneliness and was unable to detect an overall effect of the interventions on social support [SMD: 0.00; 95% CI: -0.11 to 0.12]. DISCUSSION: The results show interventions can potentially reduce loneliness in the non-institutionalized, community-dwelling and older population living at home. As confidence in the evidence is low, rigorous evaluation is recommended. REGISTRATION: International Prospective Register of SRs (PROSPERO): Registration number: CRD42021255625.

Artificial-Intelligence-Aided Radiographic Diagnostic of Knee Osteoarthritis Leads to a Higher Association of Clinical Findings with Diagnostic Ratings.

BACKGROUND: Radiographic knee osteoarthritis (OA) severity and clinical severity are often dissociated. Artificial intelligence (AI) aid was shown to increase inter-rater reliability in radiographic OA diagnosis. Thus, AI-aided radiographic diagnoses were compared against AI-unaided diagnoses with regard to their correlations with clinical severity. METHODS: Seventy-one DICOMs (m/f = 27:42, mean age: 27.86 ± 6.5) (X-ray format) were used for AI analysis (KOALA software, IB Lab GmbH). Subjects were recruited from a physiotherapy trial (MLKOA). At baseline, each subject received (i) a knee X-ray and (ii) an assessment of five main scores (Tegner Scale (TAS); Knee Injury and Osteoarthritis Outcome Score (KOOS); International Physical Activity Questionnaire; Star Excursion Balance Test; Six-Minute Walk Test). Clinical assessments were repeated three times (weeks 6, 12 and 24). Three physicians analyzed the presented X-rays both with and without AI via KL grading. Analyses of the (i) inter-rater reliability (IRR) and (ii) Spearman's Correlation Test for the overall KL score for each individual rater with clinical score were performed. RESULTS: We found that AI-aided diagnostic ratings had a higher association with the overall KL score and the KOOS. The amount of improvement due to AI depended on the individual rater. CONCLUSION: AI-guided systems can improve the ratings of knee radiographs and show a stronger association with clinical severity. These results were shown to be influenced by individual readers. Thus, AI training amongst physicians might need to be increased. KL might be insufficient as a single tool for knee OA diagnosis.

Deep Learning for Fully Automated Radiographic Measurements of the Pelvis and Hip.

The morphometry of the hip and pelvis can be evaluated in native radiographs. Artificial-intelligence-assisted analyses provide objective, accurate, and reproducible results. This study investigates the performance of an artificial intelligence (AI)-based software using deep learning algorithms to measure radiological parameters that identify femoroacetabular impingement and hip dysplasia. Sixty-two radiographs (124 hips) were manually evaluated by three observers and fully automated analyses were performed by an AI-driven software (HIPPO™, ImageBiopsy Lab, Vienna, Austria). We compared the performance of the three human readers with the HIPPO™ using a Bayesian mixed model. For this purpose, we used the absolute deviation from the median ratings of all readers and HIPPO™. Our results indicate a high probability that the AI-driven software ranks better than at least one manual reader for the majority of outcome measures. Hence, fully automated analyses could provide reproducible results and facilitate identifying radiographic signs of hip disorders.

Cost-Effectiveness of First- and Second-Step Treatment Strategies for Major Depressive Disorder : A Rapid Review.

BACKGROUND: Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect. PURPOSE: To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD. DATA SOURCES: Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022). STUDY SELECTION: Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria. DATA EXTRACTION: Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility. DATA SYNTHESIS: Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions. LIMITATIONS: Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available. CONCLUSION: Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions. PRIMARY FUNDING SOURCE: American College of Physicians.

Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). PURPOSE: To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. DATA SOURCES: English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. STUDY SELECTION: 2 investigators independently selected randomized trials of at least 6 weeks' duration. DATA EXTRACTION: Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. DATA SYNTHESIS: 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. LIMITATIONS: Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. CONCLUSION: Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42020204703).

Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians.

BACKGROUND: Clinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection. PURPOSE: To assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting. DATA SOURCES: Epistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022. STUDY SELECTION: Two reviewers independently screened abstracts and full texts against a priori-defined criteria. Randomized controlled trials (RCTs) that compared COVID-19 treatments in adult outpatients with confirmed SARS-CoV-2 infection were included. DATA EXTRACTION: One reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments. DATA SYNTHESIS: The 26 included studies collected data before the emergence of the Omicron variant. Nirmatrelvir-ritonavir and casirivimab-imdevimab probably reduced hospitalizations (1% vs. 6% [1 RCT] and 1% vs. 4% [1 RCT], respectively; moderate COE). Nirmatrelvir-ritonavir probably reduced all-cause mortality (0% vs. 1% [1 RCT]; moderate COE), and regdanvimab probably improved recovery (87% vs. 72% [1 RCT]; moderate COE). Casirivimab-imdevimab reduced time to recovery by a median difference of 4 days (10 vs. 14 median days [1 RCT]; high COE). Molnupiravir may reduce all-cause mortality, sotrovimab may reduce hospitalization, and remdesivir may improve recovery (low COE). Lopinavir-ritonavir and azithromycin may have increased harms, and hydroxychloroquine may result in lower recovery rates (low COE). Other treatments had insufficient evidence or no statistical difference in efficacy and safety versus placebo. LIMITATION: Many outcomes had few events and small samples. CONCLUSION: Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42022323440).

Assessing the magnitude of reporting bias in trials of homeopathy: a cross-sectional study and meta-analysis.

OBJECTIVES: To assess the magnitude of reporting bias in trials assessing homeopathic treatments and its impact on evidence syntheses. DESIGN: A cross-sectional study and meta-analysis. Two persons independently searched Clinicaltrials.gov, the EU Clinical Trials Register and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials. To determine whether registered trials were published and to detect published but unregistered trials, two persons independently searched PubMed, Allied and Complementary Medicine Database, Embase and Google Scholar up to April 2021. For meta-analyses, we used random effects models to determine the impact of unregistered studies on meta-analytic results. MAIN OUTCOMES AND MEASURES: We report the proportion of registered but unpublished trials and the proportion of published but unregistered trials. We also assessed whether primary outcomes were consistent between registration and publication. For meta-analyses, we used standardised mean differences (SMDs). RESULTS: Since 2002, almost 38% of registered homeopathy trials have remained unpublished, and 50% of published randomised controlled trials (RCTs) have not been registered. Retrospective registration was more common than prospective registration. Furthermore, 25% of primary outcomes were altered or changed compared with the registry. Although we could detect a statistically significant trend toward an increase of registrations of homeopathy trials (p=0.001), almost 30% of RCTs published during the past 5 years had not been registered.A meta-analysis stratified by registration status of RCTs revealed substantially larger treatment effects of unregistered RCTs (SMD: -0.53, 95% CI -0.87 to -0.20) than registered RCTs (SMD: -0.14, 95% CI -0.35 to 0.07). CONCLUSIONS: Registration of published trials was infrequent, many registered trials were not published and primary outcomes were often altered or changed. This likely affects the validity of the body of evidence of homeopathic literature and may overestimate the true treatment effect of homeopathic remedies.

Methods to detect inappropriate use of MRI and CT for musculoskeletal conditions: A scoping review.

OBJECTIVE: Identify and evaluate methods suitable for detecting inappropriate use of MRI or CT in the musculoskeletal system. DESIGN: Systematic review of studies that described methods to measure inappropriate use of MRI or CT in the musculoskeletal system. We used a multi-step strategy to classify identified methods into categories. These categories were then analyzed according to the data needed and their limitations. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: English or German language studies that measured inappropriate use of MRI or CT in the musculoskeletal system. Articles were also included if they reported a general approach to the measurement of inappropriate imaging regardless of body region. Expert opinions, unsystematic reviews, commentaries, articles without abstracts, and studies on cancer were excluded. RESULTS: 47 studies met the inclusion criteria. The categorization of the studies resulted in seven individual approaches to measure inappropriate use: (1) availability of meaningful diagnostic information; (2) predictors associated with imaging use; (3) comparison with guideline recommendations; (4) assessment by experts; (5) comparison or analysis of patients' paths; (6) comparison with surgery findings; (7) geographic variation. All these approaches have specific data requirements and individual advantages and disadvantages regarding risk of bias and needed data. CONCLUSIONS: We could not find a single method of choice to detect inappropriate use of MRI or CT in the musculoskeletal system. A combination of different approaches is the preferred strategy to deal with the advantages and disadvantages of the individual methods.

Thrombectomy for ischemic stroke: meta-analyses of recurrent strokes, vasospasms, and subarachnoid hemorrhages.

Mechanical thrombectomy with stent retrievers is an effective treatment for patients with ischemic stroke. Results of recent meta-analyses report that the treatment is safe. However, the endpoints recurrent stroke, vasospasms, and subarachnoid hemorrhage have not been evaluated sufficiently. Hence, we extracted data on these outcomes from the five recent thrombectomy trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA published in 2015). Subsequently, we conducted meta-analyses for each outcome. We report the results of the fixed, as well as the random effects model. Three studies reported data on recurrent strokes. While the results did not reach statistical significance in the random effects model (despite a three times elevated risk), the fixed effects model revealed a significantly higher rate of recurrent strokes after thrombectomy. Four studies reported data on subarachnoid hemorrhage. The higher pooled rates in the intervention groups were statistically significant in both, the fixed and the random effects model. One study reported on vasospasms. We recorded 14 events in the intervention group and none in the control group. The efficacy of mechanical thrombectomy is not questioned, yet our results indicate an increased risk for recurrent strokes, subarachnoid hemorrhage, and vasospasms post-treatment. Therefore, we strongly recommend a thoroughly surveillance, concerning these adverse events in future clinical trials and routine registries.

Health effects of cow's milk consumption in infants up to 3 years of age: a systematic review and meta-analysis.

OBJECTIVE: To summarize the best available evidence regarding the short- and long-term health effects of cow's milk intake in healthy, full-term infants up to 3 years of age. DESIGN: We conducted a systematic review and meta-analysis. SETTING: We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library between 1960 and July 2013 and manually reviewed reference lists of pertinent articles. Two researchers independently reviewed abstracts and full-text articles and extracted relevant data. SUBJECTS: We included (randomized/non-randomized) controlled trials and observational studies. RESULTS: We included data from twenty-three studies (one randomized controlled trial, four non-randomized controlled trials, eight case-control studies and ten cohort studies) for the evidence synthesis. Pooled results of four studies revealed a higher risk of Fe-deficiency anaemia for infants consuming cow's milk compared with those consuming follow-on formula (relative risk=3·76; 95 % CI 2·73, 5·19). For type 1 diabetes mellitus, six out of seven case-control studies did not show a difference in the risk of developing this disease based on the age of introduction of cow's milk. We did not find negative associations for other health effects. CONCLUSIONS: Cow's milk consumption in infancy is associated with an increased risk of developing Fe-deficiency anaemia. Limiting cow's milk consumption may be important to ensure an adequate Fe intake for infants and toddlers. High-quality patient information for caregivers is needed on how infants' Fe requirements can be met.