Online-Mediated HIV Pre-exposure Prophylaxis Care and Reduced Monitoring Frequency for Men Who Have Sex With Men: Protocol for a Randomized Controlled Noninferiority Trial (EZI-PrEP Study).

BACKGROUND: Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. OBJECTIVE: The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. METHODS: This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, "unprotected act") as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8. RESULTS: The results of the main analysis are expected in 2024. CONCLUSIONS: This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51023.

Point-of-care ultrasound use in emergencies: what every anaesthetist should know.

Point-of-care ultrasound has been embraced by anaesthetists as an invaluable tool for rapid diagnosis of haemodynamic instability, to ensure procedural safety and monitor response to treatments. Increasingly available, affordable and portable, with emerging evidence of improved patient outcomes, point-of-care ultrasound has become a valuable tool in the emergency setting. This state-of-the-art review describes the feasibility of point-of-care ultrasound practice, training and maintenance of competence. It also describes the many uses of point-of-care ultrasound for the anaesthetist and describes the most salient point-of-care ultrasound views for anaesthetic emergencies including: undifferentiated shock; hypoxemia; and trauma. Procedural safety is also discussed in addition to relevant important governance aspects. Cardiac function should be assessed using the parasternal long axis, parasternal short basal/mid-papillary/apical, apical four chamber and subcostal four chamber views, and should include a visual estimation of global left ventricular ejection fraction. Other cardiovascular conditions that can be identified using point-of-care ultrasound include: pericardial effusion; cardiac tamponade; and pulmonary embolism. Pulmonary emergency conditions that can be diagnosed using point-of-care ultrasound include pneumothorax; pleural effusion; and interstitial syndrome. The extended focused assessment with sonography for trauma examination may of value in patients who are hypotensive in order to identify intra-abdominal haemorrhage, pneumothoraces and haemothoraces.

Drug Survival of Oral Retinoids in Hidradenitis Suppurativa: A Real-Life Cohort Study.

INTRODUCTION: Cohort studies on the use of retinoids for hidradenitis suppurativa (HS) have yielded contradicting results. As the clinical presentation of HS is heterogeneous, with different predilection sites and hallmark features, it can be hypothesized that HS phenotypes are associated with the effectiveness of specific retinoid treatments. OBJECTIVES: The aim of this study was to evaluate the drug survival of oral retinoids in the treatment of HS and to establish predictors for longer treatment duration. METHODS: A retrospective, dual-center study was conducted in the Netherlands in adult HS patients treated with oral retinoids between 2011 and 2021. Drug survival analyses were performed through Kaplan-Meier survival curves. Additionally, Cox regression models were used to determine predictors for a longer drug survival. RESULTS: In total, 102 patients were included. Overall drug survival of (low-dose) isotretinoin (n = 66) at 12 and 24 months was 44.2% and 15.5%, respectively. Termination of treatment was mostly due to ineffectiveness (26%). Presence of widespread comedones (p = 0.03) and the use of concomitant systemic medication (p = 0.04) were associated with a prolonged treatment duration. For acitretin (n = 36), the overall drug survival was 42.0% at 12 months and 37.4% at 24 months, and was also predominantly determined by ineffectiveness (28%). Interestingly, the scarring folliculitis phenotype (p < 0.05) was associated with prolonged drug survival time for acitretin treatment relative to the regular phenotype. CONCLUSION: Comparable drug survival rates at 12 months for isotretinoin and acitretin were found. HS patients with widespread comedones and the scarring folliculitis phenotype could benefit from treatment with isotretinoin or acitretin, respectively.

Assessing stigma in low- and middle-income countries: A systematic review of scales used with children and adolescents.

INTRODUCTION: Stigmatization contributes to health inequalities, impacting the wellbeing of children and adolescents negatively. Addressing stigmatization requires adequate measurement. Our systematic review synthesizes the content of scales used with children and adolescents in low- and middle-income countries (LMICs) across stigmas, and examines their comparability and level of cultural adaptation. METHODS: Ten databases were systematically searched combining three sets of search terms: (i) stigma, (ii) scales, and (iii) LMICs. Studies conducted in LMICs, with a sample with mean age below 18 and reporting a minimum of one stigma scale, were eligible. We allocated scale items to four frameworks: (i) dimensions, or drivers of stigmatization; (ii) target variants, or types of stigmatization; (iii) socio-ecological levels, and (iv) cross-cultural equivalence, or scale adaptation to context/population. Based on percentages, we compared scale content per age cohort, stigma status, region, and stigma category. RESULTS: Out of 14,348 records, we included 93 articles (112 scales). Most studies focused on adolescents (12-18 years). Twelve scales were used more than once, seven were used across regions, and four were employed for multiple stigmas. Physical health stigma, and HIV/AIDS-related stigma in particular, was measured most; mental health and multiple/generic stigmas least. Physical and mental health scales were generally more comprehensive, i.e., measuring more stigma facets. In general, scales consistently measured two of the 21 included stigma facets, namely the disruptiveness dimension and the community level. Cross-cultural equivalence was moderate; conceptual and measurement equivalence were high. DISCUSSION: Although scales were largely comparable in how they measure stigma, they failed to reflect the complexity of the stigmatization process and fell short of existing stigma frameworks and qualitative research. Stigma research with children should work towards cross-culturally validated stigma scale sets which incorporate more facets of existing stigma frameworks, thus facilitating comparability across cultural contexts and informing intervention development and evaluation.

Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

Imaging post liver transplantation part II: biliary complications.

Biliary complications post liver transplantation are a significant source of morbidity and mortality and early recognition is paramount to the long-term success of the liver graft. Part II of this series will focus on liver transplant biliary anatomy, including the blood supply to the biliary system and potential problems if it is interrupted. The imaging rationale for investigating suspected biliary complications, potential pitfalls, and treatment options will be discussed. The various biliary complications will be illustrated using a collection of cases.

Invasive group A streptococcal infection outbreaks of typeemm118 in a long-term care facility, and of type emm74 in the homeless population, Montréal, Quebec.

BACKGROUND: Two invasive group A streptococcus (iGAS) infection outbreaks occurred in Montreal in 2016 and 2017; one in a long-term care facility (typeemm118) and one in the community, primarily involving homeless people (typeemm74). OBJECTIVE: To describe two recent iGAS outbreaks in Montréal and highlight the challenges in dealing with these outbreaks and the need to tailor the public health response to control them. METHODOLOGY: All cases of iGAS were investigated and the isolates were sent to the laboratory foremmtyping. In both outbreaks, cases of superficial group Astreptococcus(GAS) infection were identified, through 1) systematic case detection accompanied by screening for asymptomatic carriers among residents and employees of the long-term care facility and 2) sentinel surveillance among homeless people. Visits were made to community organizations providing homeless services (including shelters) and social networks were analyzed to establish whether there were any links among cases of GAS infection (both invasive and noninvasive) and locations frequented. In both outbreaks, recommendations were made to service providers regarding enhancement of infection prevention and control measures. RESULTS: In the long-term care facility, five cases of typeemm118 iGAS were identified over a 22-month period, one of which resulted in death. All residents were screened and no carriers were identified. Among the employees, 81 (65%) were screened and fourcarriers were identified. Of those, one was a carrier of typeemm118 GAS. All carriers were treated, and subsequent follow-up sampling on three carriers (including the one withemm118) was negative.In the community, 23 cases of typeemm74 iGAS were detected over a 16-month period, four of which resulted in death. Half of the cases (n=12) were described as homeless, and six others were users of services for the homeless. Sentinel surveillance of superficial infections yielded 64 cultures with GAS, chiefly on the skin, including 51 (80%) of typeemm74. An analysis of the social networks revealed the large number and variety of resources for the homeless used by the cases. Visits to the community organizations providing homeless services revealed the heterogeneity and precariousness of some of these services, the difficulties encountered in applying adequate health and hygiene measures, and the high degree of mobility amongst those who use these services. CONCLUSION: The detection and control of iGAS outbreaks in both long-term care establishments and among community organizations providing homeless services are very complex. An outbreak of iGAS can develop in the background over a long time and be easily overlooked despite cases being admitted to the hospital.Emmtyping and systematic research of previous cases of iGAS are essential tools for the detection and characterization of outbreaks. Close cooperation among public health agencies, clinical teams, community organizations and laboratories is essential for proper monitoring and the reduction of GAS transmission in the community and health care settings.

Similarity attracts: The role of personality in similarity perceptions and children's attitudes towards refugees.

Previous research has shown that children's intergroup similarity judgements are based not only on ethnicity but also on other dimensions such as sports interest. The present research investigates the role of personality in perceived similarity between ingroup children and refugee outgroup children. A study was conducted among 9- to 12-year-old children (N = 124) at two elementary schools in the Netherlands. It was predicted and found that children take into account ethnicity as well as personality (whether a child is introverted or extraverted) when judging similarity of ingroup (Dutch) and outgroup (refugee) children. Furthermore, we predicted and found that greater perceived similarity between Dutch children and refugee children was associated with more positive attitudes towards refugee children. Finally, children felt lower levels of anxiety towards an extraverted compared to an introverted refugee child. Lower anxiety, in turn, was associated with more positive attitudes towards refugee children. Theoretical and practical implications are discussed. Statement of contribution What is already known? McGlothlin et al. (2005, British Journal of Developmental Psychology, 23, 227) found that similarity ratings are based not only on ethnicity but also on sports interest. Studies among adults show that extraversion is negatively related to anxiety and positively to cross-group friendships. What does this study add? The present study shows that children also base similarity ratings on the personality trait extraversion. Higher similarity between self/ingroup and refugee children is related to positive outgroup attitudes. This study shows that extraverted children feel less anxiety to an extraverted refugee child. Lower anxiety in children is related to more positive attitudes to refugee children in general.

Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial.

BACKGROUND: Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited. OBJECTIVE: To evaluate the efficacy and short-term safety of apremilast in patients with moderate HS. METHODS: A total of 20 patients with moderate HS were randomized in a 3:1 ratio to receive blinded treatment with apremilast, 30 mg twice daily, or placebo for 16 weeks. The primary outcome was the Hidradenitis Suppurativa Clinical Response at week 16. Linear mixed effects modeling (analysis of covariance) was used to assess secondary clinical outcomes between treatment groups. RESULTS: The HS clinical response was met in 8 of 15 patients in the apremilast group (53.3%) and none of 5 patients in the placebo group (0%) (P = .055) at week 16. Moreover, the apremilast-treated patients showed a significantly lower abscess and nodule count (mean difference, -2.6; 95% confidence interval, -6.0 to -0.9; P = .011), NRS for pain (mean difference, -2.7; 95% -4.5 to -0.9; P = .009), and itch (mean difference, -2.8; 95% confidence interval, -5.0 to -0.6; P = .015) over 16 weeks compared with the placebo-treated patients. There was no significant difference in the Dermatology Life Quality Index over time between the 2 treatment groups (mean difference, -3.4; 95% confidence interval, -9.0 to 2.3; P = .230). The most frequently reported adverse events in the apremilast-treated patients were mild-to-moderate headache and gastrointestinal symptoms, which did not result in dropouts. LIMITATIONS: Small number of patients, relatively short study duration. CONCLUSION: Apremilast, at a dose of 30 mg twice daily, demonstrated clinically meaningful efficacy and was generally well tolerated in patients with moderate HS.