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The Western Journal of Emergency... Nov 2023Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food...
INTRODUCTION
Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.
METHODS
We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.
RESULTS
Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.
CONCLUSION
For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.
Topics: Child; Humans; Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Infusions, Intravenous
PubMed: 38165196
DOI: 10.5811/westjem.59099 -
The Korean Journal of Internal Medicine Jan 2024The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV.
RESULTS
A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events.
CONCLUSION
In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.
Topics: Humans; COVID-19; Respiration, Artificial; COVID-19 Drug Treatment; Patient Acuity; Adenosine Monophosphate; Alanine
PubMed: 38151918
DOI: 10.3904/kjim.2023.357 -
Sexually Transmitted Infections Feb 2024To systematically identify, evaluate, and synthesise qualitative research examining positive and negative influences affecting decision-making behaviour among black men...
AIM
To systematically identify, evaluate, and synthesise qualitative research examining positive and negative influences affecting decision-making behaviour among black men who have sex with men (BMSM) in the USA regarding use of pre-exposure prophylaxis (PrEP).
BACKGROUND
Used correctly, PrEP is highly efficacious in preventing HIV infection and is available via healthcare services throughout the USA. BMSM are a key target population for HIV prevention services, however their engagement with these services is low. With potential barriers to access ranging from systemic to personal, a phenomenological perspective on the influences affecting individuals' decision-making is essential, helping to better understand the needs of this target population and guide development and delivery of more effective future policy and intervention services.
DESIGN
Qualitative meta-synthesis with meta-aggregation.
DATA SOURCES
The electronic databases Medline, CINAHL, APA PsycInfo, Embase and Ovid Emcare were comprehensively searched from inception to 21 January 2022.
REVIEW METHODS
Systematic identification, quality assessment and synthesis of existing qualitative research according to protocols of meta-aggregation. This included identifying salient study findings and corroborating illustrations from the data, sorting like findings into descriptive themed categories and developing transformative synthesised statements from aggregate appraisal of category findings.
RESULTS
Seventeen studies met the inclusion criteria and were assessed to be of acceptable quality. Synthesis of study data yielded 30 categories grouped under five themes: Stigma, Discrimination, Mistrust, PrEP positivity and PrEP negativity. Twelve synthesised statements were produced to provide a summary of the results and suggest improvements to the delivery of future PrEP services and interventions.
CONCLUSION
A more targeted approach focused on advocacy and ambassadorship outside of clinical settings may be more influential in positive decision-making regarding use of PrEP in BMSM populations than relying on traditional outreach methods via institutions and their representatives where stigma, mistrust and structural inequalities perpetuate.
Topics: Humans; Male; Anti-HIV Agents; HIV Infections; Homosexuality, Male; Pre-Exposure Prophylaxis; Sexual and Gender Minorities; Black or African American; Decision Making
PubMed: 38148150
DOI: 10.1136/sextrans-2023-055861 -
Journal of Preventive Medicine and... Jan 2024The effectiveness and efficiency of pre-exposure prophylaxis (PrEP) in reducing the transmission of human immunodeficiency virus (HIV) among men who have sex with men... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The effectiveness and efficiency of pre-exposure prophylaxis (PrEP) in reducing the transmission of human immunodeficiency virus (HIV) among men who have sex with men (MSM) relies on how widely it is adopted and adhered to, particularly among high-risk groups of MSM. The meta-analysis aimed to collect and analyze existing evidence on various factors related to PrEP adherence in MSM, including demographic characteristics, sexual behaviors, substance use, and psychosocial factors.
METHODS
The meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search included articles published between January 2018 and December 2022, obtained from the PubMed, ScienceDirect, and Scopus databases. The studies that were included in the analysis reported the proportion of MSM who demonstrated adherence to PrEP and underwent quality appraisal using the Newcastle-Ottawa Scale.
RESULTS
Of the 268 studies initially identified, only 12 met the inclusion criteria and were included in the final meta-analysis. The findings indicated that education (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12 to 2.40), number of sexual partners (OR, 1.16; 95% CI, 1.02 to 1.31), engaging in sexual activities with an human immunodeficiency virus-positive partner (OR, 1.59; 95% CI, 1.16 to 2.26), substance use (OR, 0.83; 95% CI, 0.70 to 0.99), and lower levels of depression (OR, 0.55; 95% CI, 0.37 to 0.82) were associated with higher rates of PrEP adherence among MSM.
CONCLUSIONS
Despite these findings, further research is necessary to investigate PrEP adherence more comprehensively. The findings of this meta-analysis can be utilized to inform interventions aimed at improving PrEP adherence among MSM and provide directions for future research in this area.
Topics: Male; Humans; Homosexuality, Male; Pre-Exposure Prophylaxis; Safe Sex; HIV Infections; Anti-HIV Agents; Sexual and Gender Minorities; Sexual Behavior; Substance-Related Disorders
PubMed: 38147821
DOI: 10.3961/jpmph.23.345 -
Journal of Community Health Jun 2024In the pursuit of ending the HIV epidemic, U.S. emergency departments (EDs) have emerged as a valuable setting to increase HIV testing and linkage to care. There is... (Review)
Review
In the pursuit of ending the HIV epidemic, U.S. emergency departments (EDs) have emerged as a valuable setting to increase HIV testing and linkage to care. There is limited data available, however, describing the incorporation of HIV prevention initiatives in U.S. EDs. Over the last decade, HIV pre-exposure prophylaxis (PrEP) has significantly changed the HIV prevention landscape globally and very little is known about the provision of PrEP in U.S. EDs. To address this gap in the literature, we conducted a systematic review of peer-reviewed quantitative studies and conference abstracts spanning July 2012 - October 2022. Of 433 citations, 11 articles and 13 abstracts meet our inclusion criteria, representing 18 unique studies addressing PrEP screening, prescribing, and/or linkage to PrEP care.Most studies describe screening processes to identify PrEP-eligible patients (n = 17); most studies leveraged a patient's STI history as initial PrEP eligibility screening criteria. Fewer studies describe PrEP prescribing (n = 2) and/or linkage to PrEP care (n = 8).Findings from this systematic review highlight the potential for U.S. EDs to increase PrEP uptake among individuals at risk for HIV infection. Despite a growing number of studies exploring processes for incorporating PrEP into the ED setting, such studies are small-scale and time limited. Models providing prescribing PrEP in the ED show higher initiation rates than post-discharge engagement models. Electronic health record (EHR)-based HIV screening is valuable, but post-ED linkage rates are low. Our findings emphasize the need to establish best practices for initiating and supporting prevention effective PrEP use in the ED setting.
Topics: Humans; HIV Infections; Pre-Exposure Prophylaxis; Aftercare; Anti-HIV Agents; Patient Discharge; Emergency Service, Hospital
PubMed: 38127296
DOI: 10.1007/s10900-023-01320-7 -
Biomedicine & Pharmacotherapy =... Jan 2024Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases,... (Review)
Review
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
Topics: Animals; Male; Venoms; Sperm Motility; Peptides; Angiotensin II
PubMed: 38113629
DOI: 10.1016/j.biopha.2023.116015 -
Frontiers in Medicine 2023Direct-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma...
BACKGROUND
Direct-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma (HCC) occurrence, HCC-free survival, and liver function in patients with HCV decompensated cirrhosis remains uncertain. This study aimed to evaluate the effects of DAA treatment on this population.
METHODS
Studies were identified by searching the MEDLINE, SCOPUS, and CENTRAL databases. OS and HCC-free survival probabilities and time data were extracted from Kaplan-Meier curves. A one-stage meta-analysis using parametric Weibull regression was conducted to estimate the relative treatment effects of DAA vs. no DAA. The primary outcome was the OS rate. The secondary outcomes were HCC-free survival, HCC occurrence rate, and improvement in the Model for End-stage Liver Disease (MELD) score.
RESULTS
Eight cohorts comprising 3,430 participants (2,603 in the DAA group and 1,999 in the no-DAA group) were included. The OS probabilities at 12 and 24 months were 95 and 90% for the DAA group, respectively, compared with 89 and 80% in the no-DAA group, respectively. Hazard ratio (HR) was 0.48 (95% confidence interval (CI): 0.39, 0.60; < 0.001). The HCC-free survival probabilities at 12 and 24 months were 96 and 90%, respectively, in the former, and 94 and 85%, respectively, in the latter. The HR of HCC occurrence was 0.72 (95% CI: 0.52, 1.00; = 0.05), which suggests that DAA treatment in decompensated cirrhosis may lead to a 28% lower risk of HCC occurrence. The mean MELD score difference was -7.75 (95% CI: -14.52, -0.98; = 0.02).
CONCLUSION
Improvement in OS and MELD score is a long-term benefit of DAA treatment in patients with HCV decompensated cirrhosis, with a marginal effect of the treatment on HCC development.
PubMed: 38093978
DOI: 10.3389/fmed.2023.1295857 -
Cadernos de Saude Publica 2023The adverse effects of oral pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate are barriers to PrEP initiation and continuation. Although serious... (Meta-Analysis)
Meta-Analysis
The adverse effects of oral pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate are barriers to PrEP initiation and continuation. Although serious effects are rare and predictable, evidence for this assessment among men who have sex with men (MSM) and transgender women (TGW) is still limited. This study assesses the adverse effects of daily oral PrEP in MSM and TGW. This is a systematic review and meta-analysis of clinical trials and cohort studies on the use of daily oral PrEP selected from the PubMed/MEDLINE, Embase, LILACS, and Cochrane CENTRAL databases. Data extraction included adverse effects and changes in renal and hepatic markers. Random effects models were used to summarize the risk of adverse effects throughout the study. Heterogeneity was assessed using the Cochran's Q test and the inconsistency test (I2). The risk of bias and the certainty of the evidence were assessed using the Cochrane Collaboration recommendations. The search identified 653 references. Of these, 10 were selected. All studies assessed the eligibility of renal and hepatic markers. The use of daily oral PrEP was not associated with grade 3 or 4 adverse events (RR = 0.99; 95%CI: 0.83-1.18; I2 = 26.1%), any serious adverse event (RR = 1.04; 95%CI: 0.58-1.87; I2 = 88.4%), grade 3+4 creatinine level (RR = 0.66; 95%CI: 0.24-1.84; I2 = 79.9%), and grade 3 or 4 hypophosphatemia (RR = 0.56; 95%CI: 0.15-2.10). The certainty of the evidence ranged from high to moderate for the outcomes analyzed. Daily oral PrEP is safe and well tolerated by MSM and TGW. Adverse effects were minimal and evenly distributed between intervention and control.
Topics: Male; Humans; Female; Homosexuality, Male; Pre-Exposure Prophylaxis; Transgender Persons; Brazil; Sexual and Gender Minorities; HIV Infections; Anti-HIV Agents
PubMed: 38088646
DOI: 10.1590/0102-311XEN089522 -
The American Journal of Tropical... Jan 2024Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in... (Meta-Analysis)
Meta-Analysis
Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.
Topics: Child; Child, Preschool; Humans; Amodiaquine; Antimalarials; Artesunate; Chemoprevention; Drug Combinations; Malaria; Pyrimethamine; Seasons; Sulfadoxine; Adolescent
PubMed: 38081050
DOI: 10.4269/ajtmh.23-0481 -
Clinical Transplantation Jan 2024Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients... (Review)
Review
BACKGROUND
Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID).
METHODS
We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs.
RESULTS
Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).
CONCLUSIONS
The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
Topics: Humans; Kidney Transplantation; Cytomegalovirus; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases
PubMed: 38063324
DOI: 10.1111/ctr.15218