Daily ritonavir-boosted darunavir for viral suppression in pregnancy (DRV-P).

BACKGROUND: Ritonavir-boosted darunavir (DRV/r) is a preferred protease inhibitor in pregnant women living with HIV. Current practice at British Columbia's referral centre (the Oak Tree Clinic) is to dose DRV/r as 800/100 mg daily throughout pregnancy, although some guidelines recommend DRV/r 600/100 mg twice daily due to altered pharmacokinetics with once-daily dosing. OBJECTIVES: We describe the effect of once-daily DRV/r on viral suppression, vertical transmission, adverse drug effects and adherence in pregnant women living with HIV. METHODS: This was a retrospective analysis of pregnant women living with HIV in British Columbia. Eligible women gave birth between January 2015 and August 2021, and took DRV/r 800/100 mg daily at any time during pregnancy. RESULTS: Thirty-four women were included in this study. The mean (SD) age was 33 (5) years. Thirty (88%) women were diagnosed with HIV prior to pregnancy, with 22 (73%) having viral suppression at baseline. Four (12%) were diagnosed in pregnancy, with a median baseline viral load of 9616 copies/mL (range 8370-165 000). Viral suppression was achieved by 16 (100%), 24 (75%) and 26 (74%) women in the first, second and third trimesters, respectively. No vertical transmission occurred. This combination was well tolerated, with adverse drug effects that did not result in discontinuation or change in therapy. Most women maintained >75% adherence to once-daily DRV/r at all times during pregnancy. CONCLUSIONS: Ritonavir-boosted darunavir 800/100 mg daily appears to be an appropriate dosing strategy for pregnant women living with HIV who are able to maintain optimal adherence.

Post-partum contraception in women living with HIV.

INTRODUCTION: Rates of unintended pregnancy are higher in women living with HIV than in those without HIV. The World Health Organization and the Canadian HIV Pregnancy Planning Guidelines recommend preventing unintended pregnancies and offering contraception counselling to women living with HIV to reduce the rate of perinatal HIV transmission worldwide. No studies have assessed post-partum (PP) contraception use in women living with HIV in Canada. METHODS: We conducted a retrospective chart review including all women living with HIV followed by the Oak Tree Clinic who had a live birth between 1 January 2014 and 15 September 2019. The main objective was to quantify the proportion and types of contraception used by women living with HIV within 3 months PP and to evaluate whether contraception counselling is associated with contraception use. RESULTS: Of the 110 participants included, 79% were using contraception within 3 months PP. The most common contraception methods used were an intrauterine device in 22% of participants followed by depot-medroxyprogesterone acetate in 18% of participants. Of those intending to use contraception PP, 86% and 92% were using contraception within 3 and 12 months PP, respectively. Contraception counselling during pregnancy, and up to 3 months PP, was associated with contraception use within 3 months PP (p < 0.05). CONCLUSION: The majority of women were using contraception within 3 months PP. Having a contraception plan resulted in a high rate of contraception use. Women living with HIV should have a PP contraception plan prior to giving birth to establish the necessary steps for starting highly reliable forms of contraception. Contraception counselling was associated with contraception use and should be incorporated during pregnancy and in the immediate PP period.

Menopausal hormone therapy for women living with HIV.

People living with HIV are ageing, and a growing number of women living with HIV are entering menopause. Women living with HIV commonly have bothersome vasomotor symptoms and onset of menopause at earlier ages; both factors go on to affect quality of life and systemic health. Vasomotor symptoms and early menopause are both indications for menopausal hormone therapy; however, current evidence suggests that this therapy is seldom offered to women living with HIV. Additionally, women living with HIV have several risks to bone health and are likely to benefit from the bone-strengthening effects of menopausal hormone therapy. We present an assessment of the benefits and risks of menopausal hormone therapy in the context of HIV care and propose a practical approach to its prescription. If considered in the appropriate clinical context with discussion of risks and benefits, menopausal hormone therapy might provide substantial benefits to symptomatic menopausal women living with HIV and improve health-related quality of life.

A practical clinical guide to counselling on and managing contraception, pre-conception planning, and menopause for women living with HIV.

Background: Women represent one quarter of the population living with HIV in Canada and are an increasingly important sector of the HIV community. While some women's health issues such as cervical cancer screening and management are well addressed in HIV management guidelines, others are not. These include sexual and reproductive health factors such as contraception, pre-conception planning, and menopause. Existing literature has shown that while women living with HIV in Canada receive good HIV care based on HIV care cascade indicators, their women's health and sexual and reproductive health care needs are not being met. Methods: In this article, we present a clinical guide for clinicians providing care for women living with HIV on three key women's health topics that are under-discussed during HIV care visits: (1) contraception, (2) pre-conception planning, and (3) menopause. Results: We have summarized the most pertinent clinical factors on each topic to support straightforward counselling and present important considerations in the context of HIV-related diseases and treatment. Finally, when relevant, we have provided practical stepwise approaches for addressing each of these women's health care topics when seeing a patient during a visit. Conclusions: It is important that HIV specialists stay well-versed in the complex clinical interactions between HIV treatment and management of women's health issues.

Historique: Les femmes forment le quart de la population qui vit avec le VIH au Canada et un segment croissant de la communauté du VIH. Certains problèmes de santé des femmes, comme le dépistage et la prise en charge du cancer du col de l'utérus, sont bien couverts dans les directives sur la prise en charge du VIH, mais d'autres non. Des facteurs liés à la santé sexuelle et reproductive, tels que la contraception, la planification avant la conception et la ménopause, en font partie. Les publications scientifiques ont démontré que les femmes qui vivent avec le VIH au Canada reçoivent de bons soins du VIH en fonction des indicateurs de soins du VIH ventilés en cascade, mais que leurs besoins en matière de santé des femmes, de santé sexuelle et de santé reproductive ne sont pas respectés. Méthodologie: Dans le présent article, les auteurs proposent un guide clinique à l'intention des cliniciens qui soignent des femmes atteintes du VIH, à l'égard de trois sujets en santé des femmes qui ne sont pas assez abordés pendant les rendez-vous sur les soins du VIH : 1) la contraception, 2) la planification avant la conception et 3) la ménopause. Résultats: Les auteurs ont résumé les facteurs cliniques les plus appropriés relatifs à chaque sujet pour favoriser un counseling franc et présentent des points de vue importants dans le contexte des maladies et des traitements liés au VIH. Enfin, lorsque c'est approprié, ils ont fourni une démarche pratique graduelle pour aborder chacun de ces sujets en santé des femmes lors d'un rendez-vous. Conclusions: Il est important que les spécialistes du VIH demeurent bien informés des interactions cliniques complexes entre le traitement du VIH et la prise en charge des problèmes de santé des femmes.

Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review.

Importance: Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated. Objective: To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal. Data Sources: MEDLINE and EMBASE (1946-January 2018) were searched for articles investigating symptoms and signs predictive of SAWS in adults. Reference lists of retrieved articles were also searched. Study Selection: Original studies that were included compared symptoms, signs, and risk assessment tools among patients who developed SAWS and patients who did not. Data Extraction and Synthesis: Data were extracted and used to calculate likelihood ratios (LRs), sensitivity, and specificity. A meta-analysis was performed to calculate summary LR. Results: Of 530 identified studies, 14 high-quality studies that included 71 295 patients and 1355 relevant cases of SAWS (1051 cases), seizure (53 cases), or delirium tremens (251 cases) were analyzed. A history of delirium tremens (LR, 2.9 [95% CI 1.7-5.2]) and baseline systolic blood pressure 140 mm Hg or higher (LR, 1.7 [95% CI, 1.3-2.3) were associated with an increased likelihood of SAWS. No single symptom or sign was associated with exclusion of SAWS. Six high-quality studies evaluated combinations of clinical findings and were useful for identifying patients in acute care facilities at high risk of developing SAWS. Of these combinations, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was most useful, with an LR of 174 (95% CI, 43-696; specificity, 0.93) when patients had 4 or more individual findings and an LR of 0.07 (95% CI, 0.02-0.26; sensitivity, 0.99) when there were 3 or fewer findings. Conclusions and Relevance: Assessment tools that use a combination of symptoms and signs are useful for identifying patients at risk of developing severe alcohol withdrawal syndrome. Most studies of these tools were not fully validated, limiting their generalizability.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

BACKGROUND: In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. OBJECTIVE: This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. METHODS: We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. RESULTS: Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400. CONCLUSIONS: Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More research is needed to determine the relationships between vancomycin trough concentrations, AUC/MIC, and clinical outcomes.

Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review.

Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors. Fifteen systematic reviews and 169 original articles were quality assessed and integrated into a descriptive review. Best evidence, which included one or more prospective studies, suggested that lower exposure to sunlight and/or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses, but a similar quality of evidence was lacking for disease progression. Prospective studies indicated that cigarette smoking may increase the risk of MS as well as accelerate disease progression, but whether smoking altered the risk of a relapse was largely unknown. Infections were implicated in both risk of developing MS and relapses, but data for progression were lacking. Specifically, exposure to the Epstein-Barr virus, particularly if this manifested as infectious mononucleosis during adolescence, was associated with increased MS risk. Upper respiratory tract infections were most commonly associated with an increase in relapses. Relapse rates typically dropped during pregnancy, but there was no strong evidence to suggest that pregnancy itself altered the risk of MS or affected long-term progression. Emerging research with the greatest potential to impact public health was the suggestion that obesity during adolescence may increase the risk of MS; if confirmed, this would be of major significance.

Learner : preceptor ratios for practice-based learning across health disciplines: a systematic review.

CONTEXT: Practice-based learning is a cornerstone of developing clinical and professional competence in health disciplines. Practice-based learning systems have many interacting components, but a key facet is the number of learners per preceptor. Different learner : preceptor ratios may have unique benefits and pose unique challenges for participants. This is the first comprehensive systematic review of the topic. Our research questions were: What are the benefits and challenges of each learner : preceptor ratio in practice-based learning from the perspectives of the learners, preceptors, patients and stakeholder organisations (i.e. the placing and health care delivery organisations)? Are any ratios superior to others with respect to these characteristics and perspectives? METHODS: Qualitative systematic review of published English-language literature since literature database inception, including multiple health disciplines. RESULTS: Seventy-three articles were included in this review. Eight learner : preceptor ratio arrangements were identified involving nursing, physiotherapy, occupational therapy, pharmacy, dietetics, speech and language therapy, and medicine. Each arrangement offers unique benefits and challenges from the perspectives of learners, preceptors, programmes and health care delivery organisations. Patient perspectives were absent. Despite important advantages of each ratio for learners, preceptors and organisations, some of which may be profession specific, the 2 : 1 and 2+ : 2+ learner : preceptor ratios appear to be most likely to successfully balance the needs of all stakeholders. CONCLUSIONS: Regardless of the learner : preceptor ratio chosen for its expected benefits, our results illuminate challenges that can be anticipated and managed. Patient perspectives should be incorporated into future studies of learner : preceptor ratios.