Gerberi, Dana

SummaryThe thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild‐type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty‐two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9–5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9–16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.

Background. Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. Methods. We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. Results. We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. Conclusions. Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

Abstract Clozapine is an effective antipsychotic medication used for treatment‐resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life‐threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine‐associated inflammatory processes, and (iii) monitoring non‐specific signs and symptoms of inflammation. Elevated levels of C‐reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4–8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine‐associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence‐based guidelines for the monitoring of clozapine‐associated inflammation.

Pulmonary auscultation is essential for detecting abnormal lung sounds during physical assessments, but its reliability depends on the operator. Machine learning (ML) models offer an alternative by automatically classifying lung sounds. ML models require substantial data, and public databases aim to address this limitation. This systematic review compares characteristics, diagnostic accuracy, concerns, and data sources of existing models in the literature. Papers published from five major databases between 1990 and 2022 were assessed. Quality assessment was accomplished with a modified QUADAS-2 tool. The review encompassed 62 studies utilizing ML models and public-access databases for lung sound classification. Artificial neural networks (ANN) and support vector machines (SVM) were frequently employed in the ML classifiers. The accuracy ranged from 49.43% to 100% for discriminating abnormal sound types and 69.40% to 99.62% for disease class classification. Seventeen public databases were identified, with the ICBHI 2017 database being the most used (66%). The majority of studies exhibited a high risk of bias and concerns related to patient selection and reference standards. Summarizing, ML models can effectively classify abnormal lung sounds using publicly available data sources. Nevertheless, inconsistent reporting and methodologies pose limitations to advancing the field, and therefore, public databases should adhere to standardized recording and labeling procedures.

AbstractBackgroundPneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests’ performance in detecting PCP.MethodsFive databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.ResultsEleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90–0.99), and specificity was 0.96 (95% CI, 0.92–0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01–0.05) and 19.31 (95% CI, 10.26–36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78–0.99) and 0.93 (95% CI, 0.80–0.98) and a specificity of 0.96 (95% CI, 0.88–0.99) and 0.98 (95% CI, 0.76–1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90–0.98) and 0.94 (95% CI, 0.84–0.98), respectively. The overall confidence in the estimates was low.ConclusionsDespite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Introduction The public health crisis of escalating mental health, behavioural and substance-related emergencies has revealed the need to approach these complex events from a health perspective, rather than the traditional criminal justice standpoint. Despite law enforcement officers often being the first responders to emergency calls concerning self or bystander harm, they are not optimally equipped to manage these crises holistically or to connect affected individuals to necessary medical treatment and social support. Paramedics and other emergency medical services (EMS) providers are well positioned to deliver comprehensive medicosocial care during and in the immediate aftermath of these emergencies, moving beyond their traditional role in emergency evaluation, stabilisation and transport to a higher level of care. The role of EMS in bridging this gap and helping shift emphasis to mental and physical health needs in crisis situations has not been examined in prior reviews. Methods and analysis In this protocol, we delineate our approach to describing existing EMS programmes that focus specifically on supporting individuals and communities experiencing mental, behavioural and substance-related health crises. The databases to be searched are EBSCO CINAHL, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline, Ovid PsycINFO and Web of Science Core Collection, with search date limits being from database inception to 14 July 2022. A narrative synthesis will be completed to characterise populations and situations targeted by the programmes, describe programme staffing and composition, detail the interventions and identify collected outcomes. Ethics and dissemination All data in the review will be publicly accessible and published previously, so approval by a research ethics board is not needed. Our findings will be published in a peer-reviewed journal and shared with the public. Trial registration number https://doi.org/10.17605/OSF.IO/UYV4R

AbstractBackgroundCanalith repositioning maneuvers (such as the Epley maneuver) are recommended by specialty guidelines for management of benign paroxysmal positional vertigo (BPPV) yet are frequently underutilized in the emergency department (ED).MethodsWe conducted a systematic review (SR) of SRs to summarize the evidence of Epley maneuver for the treatment of posterior canal (pc) BPPV in any setting. We included SRs of randomized controlled trials (RCTs) that compared Epley to control in adult patients with pc‐BPPV. Titles, abstracts, and full texts were screened in duplicate. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was used to rate certainty of evidence. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Meta‐analysis of individual studies was conducted with random and fixed effects.ResultsFrom 2228 titles, seven SRs were selected for quality assessment. One review was of higher methodological quality, included only RCTs, and was the most current and comprehensive. Five of the 11 RCTs of the review, including 312 patients with pc‐BPPV diagnosed by Dix–Hallpike, were relevant to our question. Meta‐analysis of four RCTs (251 patients) showed the use of Epley (compared to control) was associated with higher complete resolution of vertigo at 1 week (OR 7.19, 95% CI 1.52–33.98, moderate certainty). Meta‐analysis of three RCTs (195 patients) showed the use of Epley was associated with higher conversion to negative Dix–Hallpike at 1 week (OR 6.67, 95% CI 1.52–33.98, moderate certainty). The number‐needed‐to‐treat was three. Meta‐analysis of the outcomes at 1 month, and when observational studies were included, showed similar results. No serious adverse effects were reported.ConclusionsSymptoms of pc‐BPPV improve with the Epley maneuver. Emergency clinicians should become familiar with performing the Epley for BPPV. Further studies on ED implementation and clinician education of Epley are needed.

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform.

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25–3.37, p = 0.005, I 2 = 0%) and die (OR 1.62, 95% CI 1.19–2.21, p = 0.002, I 2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55–6.09, p = 0.33, I 2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.

AbstractBackground and ObjectivesSubstance use disorders (SUDs) are chronic relapsing diseases characterized by significant morbidity and mortality. Phenomenologically, patients with SUDs present with a repeating cycle of intoxication, withdrawal, and craving, significantly impacting their diagnosis and treatment. There is a need for better identification and monitoring of these disease states. Remote monitoring chronic illness with wearable devices offers a passive, unobtrusive, constant physiological data assessment. We evaluate the current evidence base for remote monitoring of nonalcohol, nonnicotine SUDs.MethodsWe performed a systematic, comprehensive literature review and screened 1942 papers.ResultsWe found 15 studies that focused mainly on the intoxication stage of SUD. These studies used wearable sensors measuring several physiological parameters (ECG, HR, O2, Accelerometer, EDA, temperature) and implemented study‐specific algorithms to evaluate the data.Discussion and ConclusionsStudies were extracted, organized, and analyzed based on the three SUD disease states. The sample sizes were relatively small, focused primarily on the intoxication stage, had low monitoring compliance, and required significant computational power preventing “real‐time” results. Cardiovascular data was the most consistently valuable data in the predictive algorithms. This review demonstrates that there is currently insufficient evidence to support remote monitoring of SUDs through wearable devices.Scientific SignificanceThis is the first systematic review to show the available data on wearable remote monitoring of SUD symptoms in each stage of the disease cycle. This clinically relevant approach demonstrates what we know and do not know about the remote monitoring of SUDs within disease states.