Eicosapentaenoic acid versus placebo as adjunctive therapy in chronic migraine: A randomized controlled trial.

OBJECTIVE: This study was conducted to assess the efficacy of daily 2000 mg eicosapentaenoic acid (EPA) supplementation in individuals with chronic migraine. BACKGROUND: Chronic migraine is characterized by a minimum of 15 headache days/month, necessitating a focus on preventive treatment strategies. EPA, a polyunsaturated fatty acid recognized for its anti-inflammatory properties, is examined for its potential effectiveness in chronic migraine management. METHODS: A randomized, blinded, placebo-controlled trial of eligible participants with a confirmed diagnosis of chronic migraine were enrolled. The intervention group received 1000 mg of EPA twice daily for 8 weeks, while the control group received two placebo softgels. Symptoms were recorded at 4 and 8 weeks. The primary outcome was assessed using the Headache Impact Test-6 to evaluate changes in patients. Secondary outcomes encompassed migraine headache days, headache severity measured via a visual analog scale, and the number of consumed painkillers. Descriptive analyses were reported in mean (± standard deviation [SD]). RESULTS: A total of 60 patients were included in the study and finally, 56 patients completed the study according to the protocol, including 47 (84%) females. The data comparison at baseline did not show any significant difference between the two groups except in the number of patients using valproic acid as prophylaxis (21 patients in the EPA group, and 13 in the placebo group; p = 0.037). The results showed after 8 weeks, a mean (SD) difference of Headache Impact Test-6 in the EPA and placebo groups was -6.96 (3.34) and -4.43 (5.24), respectively (p = 0.084). Regarding migraine headache days, participants reported a mean (SD) -9.76 (4.15) and -4.60 (4.87) decline in days with headache, respectively (p < 0.001). The number of attacks per month after 8 weeks was 3.0 (95% confidence interval [CI] 2.0-4.0) and 4.0 (95% CI 3.0-6.0), respectively (p < 0.001). Regarding severity, there was no significant difference between the two groups (mean [SD] difference: -0.76 [1.13] and -0.73 [1.04], respectively; p = 0.906). In terms of adverse events, two patients in the EPA group reported intolerable nausea and vomiting, and one patient in the placebo group reported dizziness. CONCLUSIONS: This study's findings support the potential of a daily 2000 mg EPA as a prophylactic pharmacotherapy in chronic migraine management, specifically in mitigating migraine attacks, migraine headache days, and overall quality of life.

Integrated PrEP and STI Services for Transgender Women in Uganda: Qualitative Findings from a Randomized Trial.

Tenofovir alafenamide fumarate (F/TAF) pre-exposure prophylaxis (PrEP) is understudied in sub-Saharan Africa. The Tandika PrEP study was a randomized trial that evaluated same-day F/TAF initiation, the impact of drug-level feedback on PrEP adherence, and integrated PrEP and sexually transmitted infection (STI) services for HIV-negative transgender women (TGW) in Uganda (NCT04491422). From April 2022-February 2023, a qualitative sub-study of 30 in-depth interviews explored (1) perspectives on same-day initiation of F/TAF PrEP, (2) experiences of urine tenofovir testing and drug-level feedback, and (3) descriptions of self-collection of samples for STI testing. Qualitative data were analyzed using an inductive content analytic approach. Integrated PrEP/STI services were valued by TGW because the convenience of urine testing motivated adherence and allowed for tenofovir and STI detection. (1) Preferred characteristics: F/TAF-based PrEP was easy to take and not readily identifiable as an HIV-related medication, resulting in less stigma than the better-known tenofovir disoproxil fumarate (F/TDF). Weight gain associated with F/TAF use was viewed positively by TGW as a symbol of health and prosperity in African settings. (2) Adherence motivation: PrEP adherence was motivated by a desire not to disappoint healthcare workers; TGW reciprocated adherence support and drug-level feedback by taking PrEP. (3) Facilitating adherence and STI care: Urine testing enhanced STI detection and treatment. Utilization of urine for tenofovir and STI testing motivated the uptake of HIV/STI care, emphasizing the importance of integrated PrEP and STI services. Integrating PrEP/STI services into differentiated delivery models could increase prevention uptake in this vulnerable population.

Identifying Effective Strategies for Improving Engagement in HIV Prevention and Care Among Transgender Persons in the United States: A Systematic Review.

This systematic review synthesized published literature (2000 - 2023) to identify HIV interventions specifically designed for transgender persons in the United States (PROSPERO registration number: CRD42021256460). The review also summarized strategies for improving outcomes related to the four pillars of the Ending the HIV Epidemic (EHE) initiative in the United States: Diagnose, Treat, Prevent, and Respond. A comprehensive search was conducted using the Centers for Disease Control and Prevention's HIV Prevention Research Synthesis Project database, which included over 120,000 citations from routine systematic searches in CINAHL, EMBASE, Global Health, MEDLINE, PsycInfo, and Sociological Abstracts. Of 23 interventions that met inclusion criteria, 94% focused on transgender women of color and 22% focused on young transgender persons aged 15-29 years old. Most interventions focused on Treat or Prevent, few focused on Diagnosis, and none focused on Respond. Twenty interventions (87%) showed improvement in at least one EHE related outcome and a quarter of these effective interventions were tested with randomized controlled trials. Common strategies observed in effective interventions include the following: engaging the community in intervention development; pilot-testing with the focus population to ensure appropriateness and acceptability; addressing social determinants of health (e.g. stigma, discrimination, violence) through empowerment and gender-affirming approaches; increasing access to care, prevention, and services through co-location and one-stop shop models; and utilizing peer-led counseling, education, support, and navigation. Continuous effort is needed in addressing gaps, including more research for transgender men and rural settings and for how best to adopt and adapt best practices for subgroups of transgender population.

RESUMEN: Esta revisión sistemática sintetizó la literatura publicada (2000 ­ 2023) para identificar intervenciones relacionadas con el VIH diseñadas específicamente para personas transgénero en los Estados Unidos y resumió las estrategias para mejorar los resultados relacionados con los cuatro pilares de la iniciativa Poner fin a la Epidemia del VIH (EHE por sus siglas en inglés). Diagnosticar, Tratar, Prevenir y Responder. Este protocolo de estudio se registró en PROSPERO (CRD42022364101). Se realizó una búsqueda exhaustiva utilizando la base de datos del Proyecto de Síntesis de Investigación sobre Prevención del VIH de los Centros para el Control y la Prevención de Enfermedades, que incluyó más de 120.000 citas de búsquedas sistemáticas de rutina en CINAHL, EMBASE, Global Health, MEDLINE, PsycInfo y Sociological Abstracts. De las 23 intervenciones que cumplieron con los criterios de inclusión, el 94% se centró en mujeres transgénero de color y el 22% se centró en personas transgénero jóvenes de entre 15 y 29 años. La mayoría de las intervenciones se centraron en los pilares Tratar o Prevenir, pocas se centraron en el pilar de Diagnóstico y ninguna se centró en el pilar de Responder. Veinte intervenciones (87%) mostraron una mejora en al menos un resultado relacionado con la EHE; una cuarta parte de estas intervenciones efectivas se probaron con ensayos controlados aleatorios. Las intervenciones efectivas en todos los pilares compartían características comunes, como la participación de la comunidad en el desarrollo de la intervención; la realización de pruebas piloto con la población objetivo para garantizar la idoneidad y la aceptabilidad; el abordaje de los determinantes sociales de la salud (p.e., el estigma, la discriminación, la violencia, los problemas legales, la vulnerabilidad económica, la vivienda, el transporte, la alimentación) mediante enfoques de empoderamiento y afirmación de género; el aumento del acceso a la atención, la prevención y el servicio (p.e., Mediante la co-ubicación, y el sistema de ventanilla única); y el uso de asesoramiento, educación, apoyo y orientación dirigidos por pares. Se necesita un esfuerzo continuo para abordar las brechas, incluida una mayor investigación para los hombres transgénero y los entornos rurales y para determinar cuál es la mejor manera de adoptar y adaptar las mejores prácticas para los subgrupos de la población transgénero.

Venous Thromboembolism Incidence, Risk Factors, and Prophylaxis in Burn Patients: a National Trauma Database Study.

Comprehensive studies on the incidence, risk factors, and prophylactic measures related to venous thromboembolism (VTE) are lacking in burn care. This study characterizes VTE risk and existing prevention measures to improve and inform overall patient care in the field of burn care on a national scale. The US National Trauma Data Bank (NTDB) was queried from 2007 to 2021 to identify burn-injured patients. Descriptive statistics and multivariate regression analyses were used to explore the association between demographic/clinical characteristics and VTE risk as well as compare various VTE chemoprophylaxis types. There were 326,614 burn-injured patients included for analysis; 5,642 (1.7%) experienced a VTE event during their hospitalization. Patients with VTE were significantly older, had greater BMIs and %TBSA, and were more likely to be male (p<0.001). History of smoking, hypertension or myocardial infarction, and/or substance use disorder were significant predictors of VTE (p<0.001). Patients who received low molecular weight heparin (LMWH) were less likely to have VTE compared to patients treated with heparin when controlling for other VTE risk factors (OR: .564 95% CI .523-.607, p<0.001). Longer time to VTE chemoprophylaxis (>6 hours) initiation was significantly associated with VTE (OR=1.04 95% CI 1.03=1.07, p<0.001). This study sheds light on risk factors and chemoprophylaxis in VTE to help guide clinical practice when implementing prevention strategies in burn patients. This knowledge can be leveraged to refine risk stratification models, inform evidence-based prevention strategies, and ultimately enhance the quality of care for burn patients at risk of VTE.

Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022.

Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83-2.14), living with HIV (aHR = 1.83, 95% CI = 1.12-1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61-1.97) were associated with syphilis diagnosis. Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council.

Randomized controlled trial of pre-transplant zoledronate versus observation for prevention of bone loss in allogeneic hematopoietic cell transplantation.

Background: Approximately half of allogeneic hematopoietic cell transplantation (HCT) recipients experience significant bone loss in the early post-HCT period. Only recently have international guidelines started recommending early screening. However, the guidance for intervention remains conservative. In this study, we sought to evaluate the efficacy of pre-transplant prophylactic zoledronate in preventing early bone loss in allogeneic HCT recipients. Methods: This was an open-label, investigator-initiated, phase 2 randomized controlled trial (RCT) of prophylactic zoledronate versus observation to prevent bone loss in allogeneic HCT recipients. Recipients aged ≥ 18 years of age were included after informed consent and randomized to prophylactic zoledronate 4 mg pre-HCT or observation in a 1:1 ratio. The primary outcome of the study was bone mineral density (BMD) loss at the femoral neck (FN), total hip (TH), and lumbar spine (LS), as assessed using dual-energy X-ray absorptiometry (DXA) on day+100 post-HCT. The secondary outcomes included BMD loss on day+365 and Z scores on day+100 and day+365 at the FN, TH, and LS sites. Results: The trial was terminated because the interim analysis showed a significant benefit in the intervention arm, with 50% planned recruitment. A total of 40 patients were randomized to the zoledronate and control arms. Both arms were matched for age, sex, diagnosis, pre-HCT steroid exposure, body mass index, human leukocyte antigen (HLA) match, and conditioning intensity. The grade 2-4 acute graft versus host disease (GVHD) incidences were comparable. The primary endpoint of BMD loss at FN and TH at day+100 was significant (5.62% vs. -6.78%, p = 0.009, -1.59 vs. -3.98, p = 0.016, respectively). There was no difference in the secondary endpoint of BMD loss on day+365 compared to that on day+100 or baseline at any BMD site. There was no difference in the Z-scores at any site on day+100 or day+365. Conclusions: Prophylactic zoledronate prevented early bone loss on day+100. The indicated preemptive zoledronate beyond day+100 in recipients prevented further bone loss. Patients receiving prophylactic zoledronate may benefit from a supplementary dose of the indicated preemptive zoledronate.

Interventional antibiotic treatment replacing antibiotic prophylaxis during allogeneic hematopoietic stem cell transplantation is safe and leads to a reduction of antibiotic administration.

Patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) face an elevated risk of infection-related mortality, particularly during the pre-engraftment period. Although systemic antibiotic prophylaxis (SAP) is commonly employed during neutropenia, it is linked to disruptions in the intestinal microbiome, increasing the risk of graft-versus-host disease (GVHD), Clostridium difficile infection (CDI), and colonization with multi-drug resistant (MDR) bacteria. In our retrospective analysis, we evaluated the safety and efficacy of an exclusively interventional antibiotic treatment (IAT) compared to SAP in adult alloHSCT patients. In comparison to SAP, IAT resulted in a significantly reduced duration of antibiotic therapy (24 vs. 18 days, p < 0.001), although the cumulative incidence (CI) of bloodstream infections (BSI) by day + 100 post-HSCT was significantly higher in the IAT group compared to SAP (40% vs. 13%, p < 0.001). However, this did not lead to a significant increase in ICU transfers (13% vs. 6%, p = ns) or a higher CI of non-relapse mortality (NRM) at 3 years (11% vs. 10%, p = ns). With a median follow-up of 1052 days, the 3-year overall survival (OS) rates were 69% and 66% for the SAP and IAT cohorts, respectively (p = ns). The CI of acute GVHD grade II-IV (30% vs. 39%) at 100 days or chronic GVHD of any grade (50% vs. 45%) at 3 years did not differ significantly between the SAP and IAT groups. There was a tendency towards a higher CI of severe chronic GVHD in the SAP cohort (28% vs. 13%, p = 0.08). Our single center experience in conducting alloHSCT without antibiotic prophylaxis but with stringent guidelines for prompt antibiotic intervention demonstrated no disadvantages in terms of OS and NRM. IAT led to significantly reduced consumption of cefotaxime, carbapenem, and glycopeptide antibiotics. In conclusion, our findings suggest that replacing SAP with the proposed IAT procedure is both safe and feasible.

Effectiveness of Fosphenytoin and Levetiracetam to Prevent Posttraumatic Seizures in Young Children with Accidental or Abusive Traumatic Brain Injury.

BACKGROUND: Seizures occur frequently in pediatric patients with traumatic brain injury (TBI), particularly abusive head trauma (AHT). There are limited data on the effectiveness of fosphenytoin and levetiracetam to prevent posttraumatic seizures. METHODS: We performed a retrospective single center cohort study of children < 3 years old admitted with mild [Glasgow Coma Scale (GCS) score 13-15], moderate (GCS 9-12), and severe (GCS 3-8) TBI at a level I trauma center from 2011 to 2021. Antiseizure medications were used at the discretion of the treating physicians. Nonparametric tests were used to compare antiseizure medication prophylaxis and TBI etiology. RESULTS: A total of 717 patients (263 with AHT, 454 with accidental TBI) were included, of whom 135 (19%) received fosphenytoin, 152 (21%) received levetiracetam, and 430 (60%) did not receive any seizure prophylaxis. Over the study period, the use of fosphenytoin prophylaxis decreased (R2 = 0.67, p = 0.004), whereas the use of levetiracetam increased (R2 = 0.51, p = 0.008). Additionally, the occurrence of early posttraumatic seizures decreased (R2 = 0.58, p = 0.006). Children with AHT were more likely to receive any seizure prophylaxis than those with accidental TBI (52% vs. 27%; p < 0.001) and were more likely to have ≥ 1 seizure during hospitalization (22% vs. 4%; p < 0.001). Among children who received seizure prophylaxis, those who received fosphenytoin had a higher occurrence of seizures than those who received levetiracetam (33% vs.18%; p = 0.004). After controlling for age, admission year, TBI mechanism, and severity of injury, we observed no differences in seizure occurrence between groups. CONCLUSIONS: In children < 3 years old with TBI, no differences were observed in occurrence of seizures between patients who received fosphenytoin and patients who received levetiracetam prophylaxis after controlling for patient factors including severity of injury. Levetiracetam may be an equally effective alternative to fosphenytoin for seizure prophylaxis for early posttraumatic seizure prevention in this age group.

Needle stick injuries and post-exposure prophylaxis practices among healthcare personnel working at tertiary care hospitals in Punjab, Pakistan.

BACKGROUND: Healthcare workers face a high risk of blood-borne infections due to needlestick injuries, especially in developing countries like Pakistan. OBJECTIVE: This study aims to evaluate the prevalence of needlestick injuries, reporting practices, and post-exposure prophylaxis measures among healthcare personnel in tertiary care hospitals in Punjab. METHODS: A cross-sectional study was conducted from May to July 2019. Data were collected from healthcare personnel working in teaching hospitals across six randomly selected cities of Punjab. Data were collected from 600 healthcare personnel using a pretested, self-administered questionnaire, employing stratified random sampling to ensure representative sampling. Descriptive statistics were applied, and differences in needlestick injuries across demographic segments were assessed using the Mann-Whitney U and Kruskal-Wallis H tests. RESULTS: Among the 600 respondents, 533 returned the complete questionnaire, yielding a response rate of 88.8%. The majority of respondents were female (n = 341, 64.2%). The mean years of service was 5.58 (±5.78), with most participants falling in the 0.5-5 years category (n = 338, 66.4%). The prevalence of self-reported needlestick injuries in the last six months was 35.25%. Most injuries occurred during sampling (n = 95, 35.85%), followed by recapping (n = 63, 23.77%). Reporting of needlestick injuries to the respective department was poor, with only 82 (21.87%) injuries reported. The frequency of needlestick injuries differed significantly across profession, working department, and education categories (p < 0.05). Sanitary staff were more likely to sustain needlestick injuries during garbage collection and waste handling. Post-exposure screening for blood-borne infections was received by 79 (42.93%) individuals, and post-exposure prophylaxis (PEP) was administered to 67 (36.41%). CONCLUSION: The high prevalence of needlestick injuries among healthcare personnel occurred primarily during sampling and recapping. Reporting of NSIs was inadequate, and post-exposure testing and prophylaxis practices were substandard. Enhanced policies and protocols are necessary for effective NSI surveillance and the administration of pre- and post-exposure prophylaxis.

Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

Longitudinal relationship between pre-exposure prophylaxis motivation and change in adherence among men who have sex with men in Western China.

INTRODUCTION: The efficacy of pre-exposure prophylaxis (PrEP) is highly dependent on adherence, and adherence behavior is influenced by motivation. The aim of this study was to explore the longitudinal relationship between PrEP motivation and change in adherence among men who have sex with men (MSM) in Western China. METHODS: From November 2019 to June 2021, we conducted a PrEP prospective cohort study. Motivation to take medicine was measured by the PrEP Motivation Scale at baseline, and was grouped into different levels of latent categories by Latent Profile Analysis (LPA). A multinomial logistic regression model was used to explore the longitudinal relationship between change in adherence (improvement, decline, no change) and different levels of PrEP motivation. RESULTS: MSM were divided into two categories of PrEP motivation, a "high motivation group" (n = 506, 69.89%) and a "low motivation group" (n = 218, 30.11%). High PrEP motivation had no significant effect on the change in short-term adherence, however, it contributed to the improvement in long-term adherence [odds ratio (OR) = 3.028 (1.100-8.332), p = 0.031]. The predictive power of the adherence model was significantly enhanced with the addition of the PrEP motivation factor. CONCLUSIONS: There was a positive correlation between high PrEP motivation at baseline and an improvement in long-term adherence. Surveillance and intervention of PrEP motivation in MSM can increase their adherence, and then promote PrEP efficacy.

Intensive oral prophylaxis does not alter the tongue microbiome in young patients with chronic kidney disease: longitudinal, randomized, controlled study.

Introduction: Gingivitis is a common intraoral disease in patients with chronic kidney disease (CKD), which poses a particular interdisciplinary challenge. We aimed to determine the influence of an intensive oral prophylaxis program (OPP) compared to standard prevention measures on the tongue microbiome of young patients with CKD. Methods: Thirty patients with CKD (mean age 14.2 ± 5.2 years) and generalized gingivitis were included. The effects of the intensive OPP were compared with standard prophylaxis according to statutory health insurance (treatment as usual, TAU) as a control. Tongue swabs were taken from the patients at baseline (t1) and after 3 (t2) and 6 (t3) months. Next-generation sequencing of 16S rDNA genes was used to quantitatively characterize microbial communities. Results: There were no differences in the abundance, richness, or diversity of the observed genera and species between the two study groups at baseline or after 3 or 6 months. Furthermore, no change in predefined gingivitis and oral health bacterial clusters were found. At the phylum level, Firmicutes were decreased after intervention in the TAU group (t2TAU 42.9 ± 7.1 to t3TAU 34.8 ± 4.7 (npairs=14), p=0.003; false discovery rate 0.02). The decrease of Firmicutes was not significant in the OPP group. Conclusions: Despite the intensity of dental prophylaxis and decreasing clinical signs of inflammation and decreasing plaque amount, no clinically relevant changes in the tongue microbiome were observed. Our results confirm the conserved and stable nature of the tongue microbiome, even in children with CKD.

Comparative efficacy of aspirin versus direct oral anticoagulants for venous thromboembolism prophylaxis following primary total hip arthroplasty or total knee arthroplasty: A systematic review and meta-analysis of randomised controlled trials.

Introduction: Venous thromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary embolisms (PE), are common after total knee (TKA) and hip arthroplasty (THA). Recent studies suggest that aspirin effectively prevents VTE following major orthopaedic surgery. This meta-analysis compares randomised controlled trials (RCTs) evaluating aspirin versus direct oral anticoagulants (DOACs) for VTE prevention after primary THA and TKA. Methods: We included RCTs from 2017 to 2023 that looked at aspirin versus DOACs for VTE prophylaxis in primary THA and TKA. A search strategy was conducted which used Boolean operators and MESH terms. Primary outcomes included VTE rates, symptomatic, asymptomatic DVT and PE. Secondary outcomes were mortality and bleeding complications. Statistical analysis was performed using REVMAN software. An odds ratio with a 95% confidence interval was generated for the pooled studies. Heterogeneity was assessed using the I 2 variable, and publication bias was evaluated with a funnel plot. Results: Seven RCTs with 3967 patients were included for analysis. Rivaroxaban 10 mg OD was compared to varying doses of aspirin (81-300 mg). There were no significant differences between the groups in the incidence of VTE (OR: 1.21, 95% CI: 0.72-2.01), PE (OR: 1.01, 95% CI: 0.39-2.61), asymptomatic DVT (OR: 1.39, 95% CI: 0.64-3.00), suspected DVT (OR: 1.13, 95% CI: 0.49-2.61) and major bleeding (OR: 0.84, 95% CI: 0.55-1.27). Discussion: Aspirin is as effective as rivaroxaban for primary thromboprophylaxis post-THA and TKA, without increased incidence of complications. Further research is needed to determine the optimal dosing regimen of aspirin and its long-term efficacy in preventing VTE. Level of Evidence: Level I.

Comparative Efficacy of Novel Biologics, Antitumour Necrosis Factor Agents, and Immunomodulators to Prevent Postoperative Recurrence in Crohn's Disease: A Systematic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Our objective was to compare the efficacy of novel biologics (like vedolizumab and ustekinumab), anti-tumour necrosis factor agents (anti-TNFs), and immunomodulators (IMMs) in preventing postoperative recurrence (POR) of Crohn's disease (CD). METHODS: We searched PubMed, Embase, and the Cochrane Library databases up to December 2023 to identify placebo-controlled, no-treatment-comparison, or positive-controlled studies for the prevention of POR in CD. Endoscopic and clinical recurrence were the primary and secondary endpoint for the efficacy assessment. We conducted traditional direct and Bayesian network meta-analyses to evaluate the preventive effects of selected drugs. Additionally, we ranked interventions based on their scores under the Surface Under the Cumulative Ranking curve (SUCRA). RESULTS: A total of 17 studies involving 2786 patients were included. In the direct meta-analysis, anti-TNFs, vedolizumab, and IMMs showed greater efficacy in preventing endoscopic POR, compared to controls (placebo or no treatment). When it came to preventing clinical POR, anti-TNFs and IMMs outperformed controls. The network meta-analysis revealed that the risk of endoscopic POR was considerably lower in patients receiving anti-TNFs, vedolizumab, and ustekinumab compared to controls. Regarding the reduction of clinical POR, only anti-TNFs showed significant efficacy compared to controls. Vedolizumab and anti-TNFs were ranked as the most effective strategies in preventing endoscopic and clinical recurrence, respectively. CONCLUSIONS: According to direct and network meta-analysis, in CD patients after surgical resection, novel biologics, especially vedolizumab, were quite effective in decreasing the risk of endoscopic POR, whereas anti-TNFs appeared to perform best in reducing the risk of clinical POR.

Perspectives on a peer-driven intervention to promote pre-exposure prophylaxis (PrEP) uptake among men who have sex with men in southern New England: a qualitative study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

Population pharmacokinetic modeling of vedolizumab for graft-versus-host disease prophylaxis in adults with allogeneic hematopoietic stem cell transplant.

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft-versus-host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open-label, dose-finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo-HSCT were analyzed using a two-compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time-varying covariates. Model selection was driven by goodness-of-fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo-HSCT, vedolizumab PK were well described by a two-compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.

Antibiotic prophylaxis for the prevention of surgical site infections following colorectal surgery: protocol for network meta-analysis of randomized trials.

BACKGROUND: Surgical site infections continue to be a significant challenge following colorectal surgery. These can result in extended hospital stays, hospital readmissions, increased treatment costs, and negative effects on patients' quality of life. Antibiotic prophylaxis plays a crucial role in preventing infection during surgery, specifically in preventing surgical site infections after colorectal surgery in adult patients. However, the optimal antibiotic regimen is still unclear based on current evidence. Considering the limitations of existing reviews, our goal is to conduct a comprehensive systematic review and network meta-analysis of randomized controlled trials to evaluate the comparative benefits and harms of available antibiotic prophylaxis regimens for preventing surgical site infections following colorectal surgery in adult patients. METHODS: We will search the Medline, EMBASE, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases to identify relevant randomized controlled trials. We will include trials that (1) enrolled adults who underwent colorectal surgeries and (2) randomized them to any systemic administration of antibiotic (single or combined) prophylaxis before surgery compared to an alternative systemic antibiotic (single or combined antibiotic), placebo, control, or no prophylactic treatment. Pairs of reviewers will independently assess the risk of bias among eligible trials using a modified Cochrane risk of bias instrument for randomized trials. Our outcomes of interest include the rate of surgical site infection within 30 days of surgery, hospital length of stay, 30-day mortality, and treatment-related adverse effects. We will perform a contrast-based network meta-analysis using a frequentist random-effects model assuming a common heterogeneity parameter. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be utilized to assess the certainty of evidence for treatment effects. DISCUSSION: By synthesizing evidence from available RCTs, this study will provide valuable insight for clinicians, patients, and health policymakers on the most effective antibiotics for preventing surgical site infection. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023434544.

Management of occupational exposure to blood and body fluids in primary care.

Primary care workplaces where occupational exposure to blood and body fluids may occur should have policies and procedures in place to manage such incidents. All healthcare workers should be immunised against hepatitis B and ideally should have documentation of their antibody response to vaccination. Knowledge of hepatitis B immune status helps streamline the response to any exposure. Most occupational exposures carry a low risk of transmission of bloodborne viruses, and management can often be undertaken in general practice. Urgent risk assessment and management is crucial. If postexposure prophylaxis for hepatitis B or HIV is required, the earlier it is given, the more likely it is to be effective. Two-drug HIV postexposure prophylaxis is now more accessible because generic formulations of the drug combination are available, and general practitioners can prescribe this on a private prescription.

First Case of HIV Seroconversion With Integrase Resistance Mutations on Long-Acting Cabotegravir for Prevention in Routine Care.

Background: Long-acting cabotegravir (CAB-LA) is highly effective for HIV prevention, but delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance were observed in trials. We report the first case in routine clinical care of HIV infection on CAB-LA with INSTI resistance. Methods: The SeroPrEP study enrolls individuals in the United States who acquire HIV on pre-exposure prophylaxis modalities to assess diagnostics, antiretroviral (ARV) drug levels, resistance, and treatment outcomes. Resistance mutations in full-length HIV-1 integrase were identified by single-genome sequencing (SGS). Cabotegravir concentrations in plasma and hair segments were measured by liquid chromatography-tandem mass spectrometry. Results: A 23-year-old gender-nonbinary person, male at birth, restarted CAB-LA 6 months after discontinuation due to losing insurance. Prior to restart, HIV-1 RNA was not detected, but 20 days elapsed before CAB-LA injection. After the second CAB-LA injection, HIV antigen/antibody returned reactive (HIV-1 RNA 451 copies/mL). SGS of plasma HIV-1 RNA identified INSTI mutation Q148R in 2/24 sequences 2 days postdiagnosis; commercial genotype failed amplification. Cabotegravir hair concentration was 0.190 ng/mg 2 weeks prediagnosis; plasma cabotegravir was high (3.37 µg/mL; ∼20× PA-IC90) 14 days postdiagnosis. Viral suppression was maintained for 6 months on darunavir/cobicistat/emtricitabine/tenofovir alafenamide, then switched to doravirine + emtricitabine/tenofovir alafenamide due to nausea. Conclusions: In this first case of HIV infection on CAB-LA with INSTI resistance in routine care, cabotegravir resistance was detected only with a sensitive research assay. Accelerated pathways to minimize time between HIV testing and CAB-LA initiation are needed to optimize acute HIV detection and mitigate resistance risk. Sustained product access regardless of insurance is imperative to reduce HIV infections on CAB-LA.