Effect of Bougie Use on First-Attempt Success in Tracheal Intubations: A Systematic Review and Meta-Analysis.

The use of a bougie, a flexible endotracheal tube introducer, has been proposed to optimize first-attempt success in emergency department intubations. We aimed to evaluate the available evidence on the association of bougie use in the first attempt and success in tracheal intubations. This was a systematic review and meta-analysis of studies that evaluated first-attempt success between adults intubated with a bougie versus without a bougie (usually with a stylet) in all settings. Manikin and cadaver studies were excluded. A medical librarian searched Ovid Cochrane Central, Ovid Embase, Ovid Medline, Scopus, and Web of Science for randomized controlled trials and comparative observational studies from inception to June 2023. Study selection and data extraction were done in duplicate by 2 independent reviewers. We conducted a meta-analysis with random-effects models, and we used GRADE to assess the certainty of evidence at the outcome level. We screened a total of 2,699 studies, and 133 were selected for full-text review. A total of 18 studies, including 12 randomized controlled trials, underwent quantitative analysis. In the meta-analysis of 18 studies (9,151 patients), bougie use was associated with increased first-attempt intubation success (pooled risk ratio [RR] 1.11, 95% confidence interval [CI] 1.06 to 1.17, low certainty evidence). Bougie use was associated with increased first-attempt success across all analyzed subgroups with similar effect estimates, including in emergency intubations (9 studies; 8,070 patients; RR 1.11, 95% CI 1.05 to 1.16, low certainty). The highest point estimate favoring the use of a bougie was in the subgroup of patients with Cormack-Lehane III or IV (5 studies, 585 patients, RR 1.60, 95% CI 1.40 to 1.84, moderate certainty). In this meta-analysis, the bougie as an aid in the first intubation attempt was associated with increased success. Despite the certainty of evidence being low, these data suggest that a bougie should probably be used first and not as a rescue device in emergency intubations.

Alexander Fleming: a second look.

In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.

Prevalence of Barrett's Esophagus and Esophageal Adenocarcinoma With and Without Gastroesophageal Reflux: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Although gastroesophageal reflux disease (GERD) symptoms are an essential criterion for Barrett's esophagus (BE) screening in most gastroenterology society guidelines, a significant proportion of BE and esophageal adenocarcinoma (EAC) cases do not endorse them. In a systematic review and meta-analysis, we aimed to study the prevalence of BE/EAC in those with and without GERD. METHODS: A systematic search was conducted through 5 major databases for studies reporting prevalence of BE/EAC in patients with and without GERD. Pooled proportions and odds ratios (ORs) of BE, long-segment BE, short-segment BE, dysplasia, and EAC in patients with and without GERD were synthesized. RESULTS: Forty-three articles (12,883 patients with GERD; 51,350 patients without GERD) were included in the final analysis. BE prevalence was 7% (95% confidence interval [CI], 5.8%-8.5%) and 2.2% (95% CI, 1.6%-3%) among individuals with and without GERD, respectively. EAC prevalence was 0.6% (95% CI, 0.4%-1%) and 0.1% (95% CI, 0%-0.2%) in those with and without GERD, respectively. The overall risks for BE (OR, 2.91; 95% CI, 2.06-4.11) and long-segment BE (OR,4.17; 95% CI, 1.78-9.77) were higher in patients with GERD, but the risk for short-segment BE (OR, 1.77; 95% CI, 0.89-3.52) did not differ between the two groups. In 9 population-based high-quality studies (2244 patients with GERD; 3724 patients without GERD), BE prevalence in patients without GERD was 4.9% (95% CI, 2.6%-9%). BE prevalence was highest in North American studies (10.6% [GERD] and 4.8% [non-GERD]). CONCLUSIONS: BE prevalence in those without GERD is substantial, particularly in large high-quality population-based studies. These data are important to factor in future BE/EAC early detection guidelines.

Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Alcohol is one of the leading causes of hepatocellular carcinoma (HCC). However, pooled estimates of HCC incidence in alcohol-associated cirrhosis have not been evaluated systematically. We performed a pooled analysis of time-to-event data to provide robust estimates for the incidence of HCC in alcohol-associated cirrhosis. METHODS: Medline, Embase, Cochrane Central Register, Scopus, and Web of Science were searched from inception to August 2021. Individual patient data were reconstructed from published Kaplan-Meier curves, and a pooled analysis of cumulative HCC incidence was performed using a random-effects model. RESULTS: We screened 5022 articles and included 18 studies (148,333 patients). In the pooled analysis, the cumulative incidence of HCC in alcohol-associated cirrhosis at 1, 5, and 10 years among studies that accounted for the competing risk of death without HCC was 1%, 3%, and 9%, respectively. A secondary analysis by traditional meta-analysis determined that the HCC incidence rate was higher in cohorts enrolled in a HCC surveillance program (18.6 vs 4.8 per 1000 person-years; P = .001) vs those who were not enrolled in a surveillance program. Meta-regression showed that diabetes, smoking, variceal bleeding, and hepatic decompensation were associated with a higher risk of HCC. CONCLUSIONS: Our analysis determined that the 5- and 10- year cumulative risk of HCC in alcohol-associated cirrhosis was 3% and 9%, respectively, with a higher incidence in cohorts that were enrolled in a HCC surveillance program. These data should be validated further in large prospective studies, and may have important implications for HCC screening and surveillance among patients with alcohol-associated cirrhosis.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Systematic review: Wearable remote monitoring to detect nonalcohol/nonnicotine-related substance use disorder symptoms.

BACKGROUND AND OBJECTIVES: Substance 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. METHODS: We performed a systematic, comprehensive literature review and screened 1942 papers. RESULTS: We 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 CONCLUSIONS: Studies 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 SIGNIFICANCE: This 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.

Comparison of Intravenous Antihypertensives on Blood Pressure Control in Acute Neurovascular Emergencies: A Systematic Review.

BACKGROUND: Acute blood pressure (BP) management in neurologic patients is paramount. Different neurologic emergencies dictate various BP goals. There remains a lack of literature determining the optimal BP regimen regarding safety and efficacy. The objective of this study was to identify which intravenous antihypertensive is the most effective and safest for acute BP management in neurologic emergencies. METHODS: Ovid EBM (Evidence Based Medicine) Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection were searched from inception to August 2020. Randomized controlled trials or comparative observational studies that evaluated clevidipine, nicardipine, labetalol, esmolol, or nitroprusside for acute neurologic emergencies were included. Outcomes of interest included mortality, functional outcome, BP variability, time to goal BP, time within goal BP, incidence of hypotension, and need for rescue antihypertensives. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to evaluate the degree of certainty in the evidence available. RESULTS: A total of 3878 titles and abstracts were screened, and 183 articles were selected for full-text review. Ten studies met the inclusion criteria; however, the significant heterogeneity and very low quality of studies precluded a meta-analysis. All studies included nicardipine. Five studies compared nicardipine with labetalol, three studies compared nicardipine with clevidipine, and two studies compared nicardipine with nitroprusside. Compared with labetalol, nicardipine appears to reach goal BP faster, have less BP variability, and need less rescue antihypertensives. Compared with clevidipine, nicardipine appears to reach goal BP goal slower. Lastly, nicardipine appears to be similar for BP-related outcomes when compared with nitroprusside; however, nitroprusside may be associated with increased mortality. The confidence in the evidence available for all the outcomes was deemed very low. CONCLUSIONS: Because of the very low quality of evidence, an optimal BP agent for the treatment of patients with neurologic emergencies was unable to be determined. Future randomized controlled trials are needed to compare the most promising agents.

Infectious Complications of Dorsal Root Ganglion Stimulation: A Systematic Review and Pooled Analysis of Incidence.

BACKGROUND AND OBJECTIVES: Dorsal root ganglion stimulation (DRGS) is a newer form of neuromodulation that targets the dorsal root ganglion. DRGS has superior efficacy in complex regional pain syndrome compared to spinal cord stimulation (SCS) and may have efficacy in other forms of chronic pain. While decades of safety data are available for SCS, there is less available safety information for DRGS. The objectives of this systematic review and pooled analysis of incidence are to determine the overall incidence of DRGS infections, incidence at each stage (trial vs implant vs revision), infection characteristics, and outcomes. MATERIALS AND METHODS: A comprehensive search of databases from January 1980 to January 2021 was conducted. RESULTS: Ten studies met inclusion criteria. Eight studies reported patients with trial data (n = 291), ten studies reported patients with implant data (n = 250), and seven studies reported data with revisions (n = 26). The pooled incidence of trial infections was 1.03% (95% CI 0.35-2.99%), implant infections was 4.80% (95% CI 2.77-8.20%), revision infections was 3.85% (95% CI 0.20-21.59%), and overall infections was 2.82% (95% CI 1.62-4.54%). There was a statistically significant difference in infection rates between the trial, implant, and revision stages, X2 (2, N = 567) = 8.9839, p = 0.01. CONCLUSIONS: This is the first systematic review and pooled analysis that followed PRISMA guidelines to report infectious complications of DRGS by stage (trial vs implant vs revision). DRGS trial appears to be low risk for infection but that risk is significantly increased with DRGS implant. Our findings highlight the need for further study of infectious complications, their risks, and optimal prophylaxis.

Emotional Resilience of Older Adults during COVID-19: A Systematic Review of Studies of Stress and Well-Being.

OBJECTIVES: To examine post-traumatic stress, depression, anxiety, and well-being in older adults under quarantine. METHODS: A systematic review of CINAHL, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science from 2000 to 2020 was conducted. Keywords included coronavirus, epidemic, quarantine, stress, mental health, and similar terms. Included studies enrolled participants under quarantine, quantitatively measured mental health or well-being, and characterized outcomes by age. RESULTS: Of 894 initial results, 20 studies met the criteria and were included. Studies comprise 106,553 participants from eight countries, ages 6-100, two epidemics (COVID-19, SARS), and 27 assessment tools. One study found greater distress in older adults relative to younger adults, one found no significant differences, and 18 found lower negative outcomes in older participants in at least one metric. CONCLUSIONS: Older adults in this review generally have lower stress and less negative emotions under quarantine than younger adults. It is unknown how this compares to pre-pandemic measures. More representative and longitudinal studies are needed to measure the impact of quarantine on the mental health of older adults. CLINICAL IMPLICATIONS: As existing scales may not capture the full extent of pandemic psychological effects on older adults, clinicians must vigilantly monitor older adults' mental health.

Risk Factors for Delirium in Older Adults in the Emergency Department: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to identify risk factors for delirium in geriatric patients in the emergency department and to identify emergency department (ED)-based modifiable risk factors for developing delirium during hospitalization. We searched evidence based medicine reviews, EMBASE, MEDLINE, Scopus, and Web of Science for observational studies from the time of their inception to July 2020. We included studies that evaluated potential risk factors for either prevalent or incident delirium among older adults (age ≥ 60 years) presenting to the ED. When appropriate, we meta-analyzed estimates for risk factors using a random-effects model. The certainty of evidence was evaluated using the grading of recommendations assessment, development and evaluation approach. The study's protocol was registered in PROSPERO (CDR42020175261). A total of 4,513 citations were reviewed, and 34 studies met the criteria for inclusion: 27 evaluating risk factors for ED delirium (13,412 patients) and 7 evaluating ED-based risk factors for developing delirium during hospitalization (2,238 patients). The prevalence of ED delirium ranged from 7% to 35%. Four factors had strong associations with ED delirium and were graded as high-certainty evidence, including nursing home residence (4 studies; odds ratio [OR], 3.45; 95% confidence interval [CI], 2.17 to 5.48), cognitive impairment (7 studies; OR, 4.46; 95% CI, 3.38 to 5.89), hearing impairment (3 studies, OR, 2.57; 95% CI, 1.03 to 6.41), and a history of stroke (3 studies; OR, 3.20; 95% CI, 1.17 to 8.75). The rate of developing delirium during hospitalization ranged from 11% to 27%. A length of stay of more than 10 hours in ED was associated with a higher risk of delirium (1 study; OR, 2.23; 95% CI, 1.13 to 4.41). One study reported that severe pain, rather than the use of opioids, was associated with the development of delirium. These findings can be used to prioritize delirium screening in the ED and develop novel ED delirium risk scores or prevention interventions.

Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

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.

The Efficacy of Physical Therapy to Alleviate Symptomatic Thoracic Radiculopathy: A Systematic Review and Meta-Narrative Analysis.

To evaluate the efficacy of physical therapy (PT) to alleviate symptomatic thoracic radiculopathy (TR) without the use of invasive procedures. Database search was conducted by an experienced medical librarian from inception until January 27, 2023, in EBSCO CINAHL with Full Text, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection. Inclusion criteria included studies that involved adult patients (age≥18) who had a magnetic resonance imaging-confirmed TR and underwent a structured, supervised PT program of any length. All types of studies were included. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. A total of 1,491 studies were screened and 7 studies met inclusion criteria, 5 case studies and 2 cohort studies. All studies showed improvement or resolution of the TR with PT. Quantitative improvements were not noted in most studies and PT regimens were sparsely described. Overall quality assessment demonstrated 3 studies had "good," 1 "fair," and 3 "poor" quality evidence. Certainty of evidence was "low" due to risk of bias. A dedicated PT program may help to alleviate symptomatic TR; however due to limited evidence, risk of bias, and low certainty in evidence, the data is too weak to support a definite conclusion.

Does Extended Reality Simulation Improve Surgical/Procedural Learning and Patient Outcomes When Compared With Standard Training Methods?: A Systematic Review.

INTRODUCTION: The use of extended reality (XR) technologies, including virtual, augmented, and mixed reality, has increased within surgical and procedural training programs. Few studies have assessed experiential learning- and patient-based outcomes using XR compared with standard training methods. METHODS: As a working group for the Society for Simulation in Healthcare, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a PICO strategy to perform a systematic review of 4238 articles to assess the effectiveness of XR technologies compared with standard training methods. Outcomes were grouped into knowledge, time-to-completion, technical proficiency, reactions, and patient outcomes. Because of study heterogeneity, a meta-analysis was not feasible. RESULTS: Thirty-two studies met eligibility criteria: 18 randomized controlled trials, 7 comparative studies, and 7 systematic reviews. Outcomes of most studies included Kirkpatrick levels of evidence I-III (reactions, knowledge, and behavior), while few reported level IV outcomes (patient). The overall risk of bias was low. With few exceptions, included studies showed XR technology to be more effective than standard training methods in improving objective skills and performance, shortening procedure time, and receiving more positive learner ratings. However, XR use did not show significant differences in gained knowledge. CONCLUSIONS: Surgical or procedural XR training may improve technical skill development among trainees and is generally favored over standard training methods. However, there should be an additional focus on how skill development translates to clinically relevant outcomes. We recommend longitudinal studies to examine retention and transfer of training to clinical settings, methods to improve timely, adaptive feedback for deliberate practice, and cost analyses.

Engaging emergency medical services to improve postacute management of behavioural health emergency calls: a protocol of a scoping literature review.

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.

Preoperative Epidural Steroid Injections and Postoperative Infections After Lumbar or Cervical Spine Surgery: A Systematic Review and Meta-Analysis.

Objective: To determine the risk difference and 95% prediction intervals (PIs) for postoperative infections (POIs) associated with preoperative epidural steroid injections (ESIs) in adults undergoing lumbar or cervical spine surgery. Methods: Comprehensive database searches were conducted from inception dates through December 2023. Inclusion criteria included all study designs involving adults receiving a preoperative ESI before lumbar or cervical decompression or fusion spine surgery. Risk of bias was assessed using a modified tool developed for uncontrolled studies. The summary estimates of risk difference and the corresponding PIs were reported. Results: A total of 12 studies were included in the systematic review, of which 9 were included in the meta-analysis. Preoperative ESIs within 1 month of lumbar spine decompression or fusion surgery were associated with a 0.6% and 2.31% greater risk of a POI, respectively. In adults ≥65 years of age, ESIs within 1 or 1-3 months of lumbar spine decompression or fusion surgery were associated with a 1.3% and 0.6% greater risk of a POI, respectively. Preoperative ESIs within 3 months of cervical spine fusion were not associated with an increased risk of a POI. The bounds of all corresponding 95% PIs were nonsignificant. Conclusion: The observations of this study provide summary estimates of risk difference and 95% PIs, which could be used to support shared decision-making about the use of ESIs before cervical or lumbar spine surgery.

A systematic review of clozapine-associated inflammation and related monitoring.

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.

Clonidine use during dexmedetomidine weaning: A systematic review.

BACKGROUND: Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms. AIM: To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults. METHODS: This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay. RESULTS: A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar. CONCLUSION: Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.

Corticosteroids for patients with vestibular neuritis: An evidence synthesis for guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: A short course of corticosteroids is among the management strategies considered by specialists for the treatment of vestibular neuritis (VN). We conducted an umbrella review (systematic review of systematic reviews) to summarize the evidence of corticosteroids use for the treatment of VN. METHODS: We included systematic reviews of randomized controlled trials (RCTs) and observational studies that evaluated the effects of corticosteroids compared to placebo or usual care in adult patients with acute VN. Titles, abstracts, and full texts were screened in duplicate. The quality of reviews was assessed with the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to rate certainty of evidence. No meta-analysis was performed. RESULTS: From 149 titles, five systematic reviews were selected for quality assessment, and two reviews were of higher methodological quality and were included. These two reviews included 12 individual studies and 660 patients with VN. In a meta-analysis of two RCTs including a total of 50 patients, the use of corticosteroids (compared to placebo) was associated with higher complete caloric recovery (risk ratio 2.81, 95% confidence interval [CI] 1.32 to 6.00, low certainty). It is very uncertain whether this translates into clinical improvement as shown by the imprecise effect estimates for outcomes such as patient-reported vertigo or patient-reported dizziness disability. There was a wide CI for the outcome of dizziness handicap score (one study, 30 patients, 20.9 points in corticosteroids group vs. 15.8 points in placebo, mean difference +5.1, 95% CI -8.09 to +18.29, very low certainty). Higher rates of minor adverse effects for those receiving corticosteroids were reported, but the certainty in this evidence was very low. CONCLUSIONS: There is limited evidence to support the use of corticosteroids for the treatment of VN in the emergency department.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis.

Background: Pneumocystis 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. Methods: Five 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. Results: Eleven 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. Conclusions: Despite 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.

Epley maneuver for benign paroxysmal positional vertigo: Evidence synthesis for guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Canalith 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). METHODS: We conducted a systematic review of systematic reviews to summarize the evidence of Epley maneuver for the treatment of posterior canal (pc) BPPV in any setting. We included systematic reviews 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 (OR) and 95% confidence intervals (CI) are reported. Meta-analysis of individual studies was conducted with random and fixed effects. RESULTS: From 2,228 titles, 7 systematic reviews 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 4 RCTs (251 patients) showed the use of Epley (as compared to control) was associated with higher complete resolution of vertigo at 1 week (OR 7.19, CI 1.52 to 33.98, moderate certainty). Meta-analysis of 3 RCTs (195 patients) showed the use of Epley was associated with higher conversion to negative Dix-Hallpike at 1 week (OR 6.67, CI 1.52 to 33.98, moderate certainty). The number-needed-to-treat was 3. Meta-analysis of the outcomes at 1 month, and when observational studies were included, showed similar results. No serious adverse effects were reported. CONCLUSIONS: Symptoms 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.