Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens.

Background: Cardiometabolic outcomes were investigated 3 years after switching to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) vs continuing 3-/4-drug tenofovir alafenamide (TAF)-based regimens in a multicenter phase 3 noninferiority study based on an open-label randomized design. Method: Adults with virologically suppressed HIV-1 switched to once-daily DTG/3TC (n = 369) or continued TAF-based regimens (n = 372). Cardiometabolic health parameters were assessed through week 144 via mixed-model repeated measures or logistic regression analyses, adjusting for baseline variables. Results: At week 144, 13% (42/316) of the DTG/3TC group and 12% (37/303) of the TAF-based regimen group had ≥10% weight gain from baseline (adjusted odds ratio, 1.11; 95% CI, .68-1.80). Adjusted change from baseline in serum leptin, a surrogate marker of adiposity, was similar between groups (treatment ratio, 1.00; 95% CI, .89-1.13). The lipid profile generally favored DTG/3TC in the baseline boosted subgroup. Adjusted odds revealed no clinically meaningful differences between groups: homeostatic model assessment of insulin resistance ≥2 (adjusted odds ratio, 0.79; 95% CI, .50-1.26), metabolic syndrome (International Diabetes Federation criteria, 0.99; .59-1.68), hepatic fibrosis (fibrosis-4 index score ≥1.45, 1.39; .63-3.06), and coronary artery disease risk (Framingham risk score ≥10%, 0.92; .56-1.49). Baseline variables and characteristics associated with odds of each cardiometabolic parameter outcome were consistent with known risk factors, including age, sex, race, and some disease characteristics. Conclusions: Cardiometabolic health 3 years after switching to DTG/3TC was comparable to that for individuals continuing TAF-based regimens, further supporting DTG/3TC as a robust switch option with a stable metabolic profile. Trial registration: ClinicalTrials.gov NCT03446573.

Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.

Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary: Report of the AAN Guideline Subcommittee.

OBJECTIVE: To update the 2011 American Academy of Neurology (AAN) guideline on the treatment of painful diabetic neuropathy (PDN) with a focus on topical and oral medications and medical class effects. METHODS: The authors systematically searched the literature from January 2008 to April 2020 using a structured review process to classify the evidence and develop practice recommendations using the AAN 2017 Clinical Practice Guideline Process Manual. RESULTS: Gabapentinoids (standardized mean difference [SMD] 0.44; 95% confidence interval [CI], 0.21-0.67), serotonin-norepinephrine reuptake inhibitors (SNRIs) (SMD 0.47; 95% CI, 0.34-0.60), sodium channel blockers (SMD 0.56; 95% CI, 0.25-0.87), and SNRI/opioid dual mechanism agents (SMD 0.62; 95% CI, 0.38-0.86) all have comparable effect sizes just above or just below our cutoff for a medium effect size (SMD 0.5). Tricyclic antidepressants (TCAs) (SMD 0.95; 95% CI, 0.15-1.8) have a large effect size, but this result is tempered by a low confidence in the estimate. RECOMMENDATIONS SUMMARY: Clinicians should assess patients with diabetes for PDN (Level B) and those with PDN for concurrent mood and sleep disorders (Level B). In patients with PDN, clinicians should offer TCAs, SNRIs, gabapentinoids, and/or sodium channel blockers to reduce pain (Level B) and consider factors other than efficacy (Level B). Clinicians should offer patients a trial of medication from a different effective class when they do not achieve meaningful improvement or experience significant adverse effects with the initial therapeutic class (Level B) and not use opioids for the treatment of PDN (Level B).

Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians. METHODS: A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. RESULTS: Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.

Long-term protection from HIV infection with oral HIV pre-exposure prophylaxis in gay and bisexual men: findings from the expanded and extended EPIC-NSW prospective implementation study.

BACKGROUND: Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. METHODS: Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790. FINDINGS: Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44). INTERPRETATION: HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk. FUNDING: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.

HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Education Research: NeuroBytes: A New Rapid, High-Yield e-Learning Platform for Continuing Professional Development in Neurology.

OBJECTIVE: To determine whether NeuroBytes is a helpful e-Learning tool in neurology through usage, viewer type, estimated time and cost of development, and postcourse survey responses. BACKGROUND: A sustainable Continuing Professional Development (CPD) system is vital in neurology due to the field's expanding therapeutic options and vulnerable patient populations. In an effort to offer concise, evidence-based updates to a wide range of neurology professionals, the American Academy of Neurology (AAN) launched NeuroBytes in 2018. NeuroBytes are brief (<5 minutes) videos that provide high-yield updates to AAN members. METHODS: NeuroBytes was beta tested from August 2018 to December 2018 and launched for pilot circulation from January 2019 to April 2019. Usage was assessed by quantifying course enrollment and completion rates; feasibility by cost and time required to design and release a module; appeal by user satisfaction; and effect by self-reported change in practice. RESULTS: A total of 5,130 NeuroBytes enrollments (1,026 ± 551/mo) occurred from January 11, 2019, to May 28, 2019, with a median of 588 enrollments per module (interquartile range, 194-922) and 37% course completion. The majority of viewers were neurologists (54%), neurologists in training (26%), and students (8%). NeuroBytes took 59 hours to develop at an estimated $77.94/h. Of the 1,895 users who completed the survey, 82% were "extremely" or "very likely" to recommend NeuroBytes to a colleague and 60% agreed that the depth of educational content was "just right." CONCLUSIONS: NeuroBytes is a user-friendly, easily accessible CPD product that delivers concise updates to a broad range of neurology practitioners and trainees. Future efforts will explore models where NeuroBytes combines with other CPD programs to affect quality of training and clinical practice.

Brief Report: Improvement in Metabolic Health Parameters at Week 48 After Switching From a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen to the 2-Drug Regimen of Dolutegravir/Lamivudine: The TANGO Study.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine was noninferior at 48 weeks to continuing 3-/4-drug tenofovir alafenamide-based regimens in virologically suppressed individuals with HIV-1. Antiretroviral agents have been associated with weight gain and metabolic complications. SETTING: One hundred thirty-four centers; 10 countries. METHODS: We assessed weight; fasting lipids, glucose, and insulin; and prevalence of insulin resistance and metabolic syndrome at baseline and week 48 in TANGO participant subgroups by boosting agent use in baseline regimens (boosted and unboosted). RESULTS: In each treatment group, 74% of participants used boosted regimens at baseline. In boosted and unboosted subgroups, weight and fasting glucose changes at week 48 were small and similar between treatment groups. Overall and in the boosted subgroup, greater decreases from baseline were observed with dolutegravir/lamivudine in fasting total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), total cholesterol/high-density lipoprotein cholesterol ratio (overall, P = 0.017; boosted, P = 0.007), and insulin (boosted, P = 0.005). Prevalence of HOMA-IR ≥2 was significantly lower at week 48 with dolutegravir/lamivudine overall [adjusted odds ratio (aOR), 0.59; 95% confidence interval (CI), 0.40 to 0.87; P = 0.008] and in the boosted subgroup [aOR, 0.56; 95% CI, 0.36 to 0.88; P = 0.012] but not in the unboosted subgroup [aOR, 0.70; 95% CI, 0.31 to 1.58; P = 0.396]. Prevalence of metabolic syndrome at week 48 was low and consistent between treatment groups overall, with differences trending to favor dolutegravir/lamivudine in the unboosted subgroup [aOR, 0.41; 95% CI, 0.15 to 1.09; P = 0.075]. CONCLUSION: Generally, switching from 3-/4-drug tenofovir alafenamide-based regimens to dolutegravir/lamivudine improved metabolic parameters, particularly when switching from boosted regimens. Because of smaller sample size in the unboosted subgroup, results warrant further investigation.

A proof-of-concept study on the impact of a chronic pain and physical activity training workshop for exercise professionals.

OBJECTIVES: Physical activity is essential for long-term chronic pain management, yet individuals struggle to participate. Exercise professionals, including fitness instructors, and personal trainers, are preferred delivery agents for education and instruction on chronic pain, physical activity, and strategies to use adherence-promoting behavioral skills. However, exercise professionals receive no relevant training during certification or continuing education opportunities to effectively support their participants living with chronic pain. Based on the ORBIT model for early pre-efficacy phases of development and testing of new behavioral treatments, the present Phase IIa proof-of-concept study was conducted. The purpose was to examine the impacts of a newly developed chronic pain and physical activity training workshop on psychosocial outcomes among exercise professionals. Outcomes included knowledge and attitudes regarding chronic pain, attitudes and beliefs about the relationship between pain and impairment, and self-efficacy to educate and instruct participants with chronic pain. METHODS: Forty-eight exercise professionals (Mage=44.4±11.0 years) participated in a three-hour, in-person workshop that was offered at one of four different locations. Participants completed pre- and post-workshop outcome assessment surveys. RESULTS: Mixed MANOVA results comparing time (pre- versus post-workshop) by workshop location (sites 1 to 4) illustrated a significant within-subjects time effect (p<0.001). All outcomes significantly improved from pre- to post-workshop (p's<0.001), demonstrating large effect sizes (partial eta-squared values ranging from 0.45 to 0.59). CONCLUSIONS: Findings offer early phase preliminary support for the effectiveness of the chronic pain and physical activity training workshop for exercise professionals. Based on ORBIT model recommendations, findings warrant future phased testing via a pilot randomized clinical trial as well as testing for impacts that trained professionals have on activity adherence among their clients living with chronic pain. Eventual workshop adoption by exercise professional certification organizations would ensure widespread and sustainable access to qualified exercise professionals to help individuals engage in physical activity. By increasing the capacity of available exercise professionals to deliver effective support, active individuals could better manage their chronic pain and live well.

Trends in practice: attitudes and challenges in the diagnosis, treatment and management of HIV infection in Australia.

As life expectancy for people living with human immunodeficiency virus (HIV) (PLWHIV) increases, management models for HIV infection are changing. To understand approaches to practice within this shifting climate and across different medical settings, in 2017 we conducted a baseline survey among the main medical practitioner groups responsible for HIV-infection care in Australia: hospital-based physicians (HBP), sexual health physicians (SHP) and 'accredited general practitioners' (referred to in 2017 study as 's100 GPs'), who are GPs authorised to prescribe HIV therapies after completing accredited national training. The follow-up survey presented here explores any changes in approaches, attitudes and challenges associated with HIV-infection management among the same practitioner groups: 17 HBP, 15 SHP and 69 accredited GP (referred to throughout as GP; includes those with sexual health diploma). Analysis of survey results showed practices remained largely similar between surveys, with a few notable exceptions. Greater consistency in attitudes, knowledge and approaches was observed between the practitioner specialty groups, with only small differences between modes of practice. A trend towards earlier initiation of HIV treatment was also identified, with a higher proportion of practitioners than baseline reporting they were comfortable beginning therapy on the day of HIV diagnosis. The impact of the introduction of two-drug therapy in Australia was also explored. Although the majority of survey respondents (and SHP in particular) expressed greater preference for three-drug compared with two-drug regimens, interest in two-drug regimens appears to be growing and may influence future prescribing practices. Addressing mental health issues for PLWHIV was again highlighted as a major priority, with practitioners overwhelmingly reporting mental health management as among their most difficult clinical challenges. Reduction in stigma/discrimination and better access to substance dependency programmes were also identified as unmet needs for this patient cohort. Consistent with our baseline survey, it appears targeted interventions and supports appropriate to this population are still required to improve overall wellbeing for PLWHIV.

Utility of rapid plasmin reagin titres in assessing treatment response and re-infection for infectious syphilis.

Background The rapid plasma reagin (RPR) assay is commonly used as a surrogate marker of infectious syphilis, but is non-specific, slow to change and variable in its rate of decline post treatment. METHODS: Within an urban sexual health service testing predominantly men who have sex with men, a file review of RPR changes was undertaken in all subjects who had a dilution level of ≥1:4, between January 2015 to the end of December 2018. RESULTS: Overall, 248 cases of infectious syphilis were identified in 215 subjects (165 HIV seropositive, 50 HIV seronegative). Among unique-subject cases with follow-up RPR recorded, seroreversion to a non-reactive titre was achieved in only 42.3% (71/168) cases at a median of 235 days (interquartile range: 138-348 days) and was significantly less likely if patients had HIV infection (P = 0.02), late latent syphilis (P = 0.003) or a subsequent syphilis infection (P < 0.0001). Having HIV infection (P = 0.03) or a subsequent episode of syphilis (P = 0.01) were associated with a lower likelihood of documented cure. CONCLUSIONS: The slow decay in RPR titres post therapy and the inability of a significant number of subjects to achieve a non-reactive result over time makes RPR a poor test for assessing the adequacy of treatment or in diagnosing re-infection, especially in populations having repeated and frequent risk exposures. As the number of syphilis cases continue to climb, better tests that accurately assess pathogen presence are urgently needed.

Trends in Geospatial Drivers of Fall-Related Hospitalizations and Asset Mapping of Fall Prevention Interventions for Vulnerable Older Adults.

Objective: Given that one in four older adults suffer potentially preventable falls annually, we aimed to identify areas with (a) delivery gaps of evidence-based programs (EBPs) targeting fall prevention among older adults, namely A Matter of Balance (AMOB), and (b) high rates of fall-related hospitalizations-hotspots. Method: Analyses included multiple geospatially linked datasets. Results: EBPs were delivered ≥1 time in 84 counties in 2012 and 90 counties in 2014. Factors associated with EPB delivery gaps (absence; p<.05) included high-density older adult areas, non-fall-related hospitalization hotspots, lower population density, nonmetropolitan areas, high-density Hispanic adult areas, and areas with limited access to home health care agencies. Hotspots for fall-related hospitalization numbered 64 in 2012 and 62 in 2014. Factors associated with hotspots included low-density older adult areas, having AMOB delivered ≥1 time annually, high population density, and high-density Hispanic adult areas. Discussion: In resource-finite settings (e.g., the aging services sector), identifying high priority areas allows for precise allocation of limited resources.

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial.

BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: A Phase IIb double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100,000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 24 (Parts I+II combined). RESULTS: 210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002). CONCLUSIONS: Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.

Rapid HIV testing increases testing frequency among gay and bisexual men: a controlled before-after study.

Background Rapid HIV testing was introduced at 12 clinics in New South Wales (NSW) for routine testing and promoted with social marketing. The effect of the availability of rapid HIV testing on testing frequency among gay and bisexual men (GBM) was evaluated. METHODS: An observational design using patient data from 12 clinics was used. The primary outcome was the mean number of HIV tests in 12 months. The intervention group comprised GBM who had one or more rapid tests from October 2013 to September 2014 and this was compared with two control groups; a concurrent group (no rapid test in the same period) and a historical group (attended between July 2011 and June 2012). Independent sample t-tests were conducted to compare mean number of tests among men in the intervention, concurrent and historical groups. Multivariate logistic regression was used to assess the association between rapid HIV testing and testing frequency. RESULTS: Men in the intervention group (n = 3934) had a mean of 1.8 HIV tests in 12 months, compared with 1.4 in the concurrent group (n = 5063; P < 0.001) and 1.4 in the historical group (n = 5904; P < 0.001); testing frequency was higher among men at increased risk of HIV in the intervention group compared with the other two groups (mean 2.2, 1.6 and 1.5 respectively; P < 0.001). Membership of the intervention group was associated with increased odds of having two or more HIV tests in 12 months (AOR = 2.5, 95%CI 2.2-2.8; P < 0.001) compared with the concurrent group, after controlling for demographic and behavioural factors. CONCLUSION: Introducing and promoting rapid HIV testing in clinics in NSW was associated with increased HIV testing frequency among GBM.

Empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection in the era of antimicrobial resistance: time to rethink?

Prudent prescribing of antimicrobials is essential in ameliorating the public health problem of antimicrobial resistance. This retrospective audit assesses whether empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection is appropriate based on laboratory confirmation.

The Honest Palm Sign: Detecting Incomplete Effort on Physical Examination.

BACKGROUND: We investigated a simple, novel diagnostic test for detecting incomplete effort during the motor portion of the neurological examination. METHODS: The results from the honest palm sign (HPS) were evaluated for 162 consecutive neuro-oncology patients who had undergone upper extremity strength testing. Deltoid, bicep, and wrist extensor strength was assessed in all patients. During the examination, patients were repeatedly encouraged to "try as hard as possible" and to "resist with all your strength." The absence of nail prints on the palms constituted a positive HPS test result (i.e., indicative of incomplete effort). The presence of nail prints constituted a negative HPS test result (i.e., indicative of full effort). RESULTS: A total of 162 patients were tested. Their mean age was 55.5 ± 14.9 years, the median Karnofsky performance scale score was 80 (range, 60-100), and 63 patients (39%) were men. Of the 162 patients, 102 (63%) had malignant gliomas, 28 (17%) had brain metastases, 21 (13%) had other primary brain tumors, and 11 (6.8%) had primary central nervous system lymphomas. Of the 162 patients, 48 (30%) had positive HPS test results. The test sensitivity (84.6%), specificity (75.2%), positive likelihood ratio (3.41), and negative likelihood ratio (0.205) were good. After excluding 33 patients with characteristics that rendered them unsuitable for testing, the results from the remaining 129 patients were analyzed. The sensitivity was unchanged (84.6%), but the specificity (96.6%), positive likelihood ratio (24.5), and negative likelihood ratio (0.16) improved dramatically. CONCLUSIONS: The HPS test is a simple, sensitive, and very specific test for detecting incomplete effort during the motor portion of neurological evaluations.

Translation of clinical trial data to changes in clinical practice: rapid transition from tenofovir disoproxil fumarate to tenofovir alafenamide-based therapies in a Sydney HIV clinic.

The transition of clinical trial data to changes in routine clinical practice is often a slow process. We describe a rapid transition of patients from one form of antiviral therapy to a modified and potentially safer version that can occur quickly when there are no financial or organisational restrictions on the prescribers.