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Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.

BACKGROUND: Primary care databases collect electronic medical records with routine data from primary care patients. The identification of chronic diseases in primary care databases often integrates information from various electronic medical record components (EMR-Cs) used by primary care providers. This study aimed to estimate the prevalence of selected chronic conditions using a large Swiss primary care database and to examine the importance of different EMR-Cs for case identification. METHODS: Cross-sectional study with 120,608 patients of 128 general practitioners in the Swiss FIRE (“Family Medicine Research using Electronic Medical Records”) primary care database in 2019. Sufficient criteria on three individual EMR-Cs, namely medication, clinical or laboratory parameters and reasons for encounters, were combined by logical disjunction into definitions of 49 chronic conditions; then prevalence estimates and measures of importance of the individual EMR-Cs for case identification were calculated. RESULTS: A total of 185,535 cases (i.e. patients with a specific chronic condition) were identified. Prevalence estimates were 27.5% (95% CI: 27.3–27.8%) for hypertension, 13.5% (13.3–13.7%) for dyslipidaemia and 6.6% (6.4–6.7%) for diabetes mellitus. Of all cases, 87.1% (87.0–87.3%) were identified via medication, 22.1% (21.9–22.3%) via clinical or laboratory parameters and 19.3% (19.1–19.5%) via reasons for encounters. The majority (65.4%) of cases were identifiable solely through medication. Of the two other EMR-Cs, clinical or laboratory parameters was most important for identifying cases of chronic kidney disease, anorexia/bulimia nervosa and obesity whereas reasons for encounters was crucial for identifying many low-prevalence diseases as well as cancer, heart disease and osteoarthritis. CONCLUSIONS: The EMR-C medication was most important for chronic disease identification overall, but identification varied strongly by disease. The analysis of the importance of different EMR-Cs for estimating prevalence revealed strengths and weaknesses of the disease definitions used within the FIRE primary care database. Although prioritising specificity over sensitivity in the EMR-C criteria may have led to underestimation of most prevalences, their sex- and age-specific patterns were consistent with published figures for Swiss general practice.

BACKGROUND: We aimed to investigate the self-reported health status and behaviours of 7th-grade adolescents, associations with gender and educational track, as well as health issues addressed during routine school doctor consultations in Switzerland. METHODS: Data on health status and behaviours, specifically general well-being, stimulant and addictive substance use, bullying/violence, exercise, nutrition and health protection, and puberty/sexuality, were drawn from routinely collected self-assessment questionnaires from 1076 (of a total of 1126) students from 14 schools in the Swiss canton of Zug in 2020. Data on health issues addressed in school doctor consultations were collected by nine school doctors (for 595 individual consultations). Multilevel logistic regression analyses were used to investigate the association of gender and educational track with unfavourable health status or behaviours. RESULTS: Although 92% (n = 989) of the students reported being happy or satisfied overall, 21% (n = 215) often or almost always felt sad, and 5-10% had repeatedly been seriously physically hurt (n = 67), sexually harassed with words (n = 88) or experienced uncomfortable physical contact (n = 60). Female gender and a lower educational track were associated with unfavourable health status. In 90% (n = 533) of the school doctor consultations, at least one topic of disease prevention or health promotion was addressed, whereby the topics addressed depended strongly on the individual school doctors. CONCLUSIONS: Our findings revealed that unfavourable health status and behaviours were prevalent among adolescents but the health topics addressed in school doctor consultations were not tailored to students’ self-reported health issues. A school-based approach that strengthens adolescents’ health literacy and provides opportunities for patient-centred counselling has the potential to improve the current and future health of adolescents and, ultimately, adults. To realise this potential, it is essential for school doctors to be sensitised and trained to address students’ health concerns. Emphasis should be placed on the importance of patient-centred counselling, the high prevalence of bullying, and gender and educational differences.

Objectives: To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland.Methods: Retrospective cohort study using nationwide hospital data (n > 8 million) and claims data from a large Swiss health insurer (n > 1 million) in 2018–2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people.Results: Inpatient psychiatric admissions in the general population decreased by 16.2% (95% confidence interval: −19.2% to −13.2%) during the first and by 3.9% (−6.7% to −0.2%) during the second pandemic shutdown, whereas outpatient mental healthcare utilization was not substantially affected. We observed distinct patterns for young people, most strikingly, an increase in mental healthcare utilization among females aged

Purpose: The frequency of medication prescribing and polypharmacy has increased in recent years in different settings, including Swiss general practice. We aimed to describe patient age- and sex-specific rates of polypharmacy and of prescriptions of the most frequent medication classes, and to explore practitioner variability in prescribing.Methods: Retrospective cross-sectional study based on anonymized electronic medical records data of 111 811 adult patients presenting to 116 Swiss general practitioners in 2019. We used mixed-effects regression analyses to assess the association of patient age and sex with polypharmacy (≥5 medications) and with the prescription of specific medication classes (second level of the Anatomical Therapeutic Chemical Classification System). Practitioner variability was quantified in terms of the random effects distributions.Results: The prevalence of polypharmacy increased with age from 6.4% among patients aged 18–40 years to 19.7% (41–64 years), 45.3% (65–80 years), and 64.6% (81–92 years), and was higher in women than in men, particularly at younger ages. The most frequently prescribed medication classes were antiinflammatory and antirheumatic products (21.6% of patients), agents acting on the renin-angiotensin system (19.9%), analgesics (18.7%), and drugs for acid related disorders (18.3%). Men were more often prescribed agents targeting the cardiovascular system, whereas most other medications were more often prescribed to women. The highest practitioner variabilities were observed for vitamins, for antiinflammatory and antirheumatic products, and for mineral supplements.Conclusion: Based on practitioner variability, prevalence, and risk potential, antiinflammatory drugs and polypharmacy in older patients appear to be the most pressing issues in current drug prescribing routines.

BackgroundChronic kidney disease (CKD) is a common condition in general practice. Data about quality and physician-level variation of CKD care provided by general practitioners is scarce. In this study, we evaluated determinants and variation of achievement of 14 quality indicators for CKD care using electronic medical records data from Swiss general practice during 2013-2019.MethodsWe defined two patient cohorts from 483 general practitioners, one to address renal function assessment in patients with predisposing conditions (n = 47,201, median age 68 years, 48.7% female) and one to address care of patients with laboratory-confirmed CKD (n = 14,654, median age 80 years, 57.5% female). We investigated quality indicator achievement with mixed-effect logistic regression and expressed physician-level variation as intraclass correlation coefficients (ICCs) and range odds ratios (rORs).ResultsWe observed the highest quality indicator achievement rate for withholding non-steroidal anti-inflammatory drug prescription in patients with CKD staged G2-3b within 12 months of follow-up (82.6%), the lowest for albuminuria assessment within 18 months of follow-up (18.1%). Highest physician-level variation was found for renal function assessment during 18 months of follow-up in patients with predisposing conditions (diabetes: ICC 0.31, rOR 26.5; cardiovascular disease: ICC 0.28, rOR 17.4; hypertension: ICC 0.24, rOR 17.2).ConclusionThis study suggests potentially unwarranted variation in general practice concerning RF assessment in patients affected by conditions predisposing for CKD. We further identified potential gaps in quality of CKD monitoring as well as lower quality of CKD care for female patients and patients not affected by comorbidities.

Understanding the decision-making strategies of general practitioners (GPs) could help reduce suboptimal antibiotic prescribing. Respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing in primary care, a key driver of antibiotic resistance (ABR). We conducted a nationwide prospective web-based survey to explore: (1) The role of C-reactive protein (CRP) point-of-care testing (POCT) on antibiotic prescribing decision-making for RTIs using case vignettes; and (2) the knowledge, attitudes and barriers/facilitators of antibiotic prescribing using deductive analysis. Most GPs (92–98%) selected CRP-POCT alone or combined with other diagnostics. GPs would use lower CRP cut-offs to guide prescribing for (more) severe RTIs than for uncomplicated RTIs. Intermediate CRP ranges were significantly wider for uncomplicated than for (more) severe RTIs (p = 0.001). Amoxicillin/clavulanic acid was the most frequently recommended antibiotic across all RTI case scenarios (65–87%). Faced with intermediate CRP results, GPs preferred 3–5-day follow-up to delayed prescribing or other clinical approaches. Patient pressure, diagnostic uncertainty, fear of complications and lack of ABR understanding were the most GP-reported barriers to appropriate antibiotic prescribing. Stewardship interventions considering CRP-POCT and the barriers and facilitators to appropriate prescribing could guide antibiotic prescribing decisions at the point of care.

Testing and prescribing vitamin B12 (also known as cobalamin) is increasing in Switzerland but substantial variation among general practitioners (GPs) with respect to testing has been noted. In this study, we aimed at exploring GPs’ mindsets regarding vitamin B12 testing and prescribing. A cross-sectional study was conducted using an online survey distributed by e-mail to Swiss GPs. The questionnaire explored mindsets related to testing and prescribing vitamin B12 in specific clinical situations, as well as testing and prescribing strategies. The questionnaire was sent to 876 GPs and 390 GPs responded (44.5%). The most controversial domains for testing and prescribing vitamin B12 were idiopathic fatigue (57.4% and 43.4% of GPs agreed, respectively) and depressive symptoms (53.0% and 35.4% of GPs agreed, respectively). There was substantial variation among GPs with regard to testing strategies (89.5% of GPS used a serum cobalamin test, 71.3% of GPS used holotranscobalamin, and 27.6% of GPs used homocysteine or methylmalonic acid). Intramuscular injection was the predominantly prescribed route of application (median of 87.5% of the prescriptions). In this study, we focus on discordant mindsets that can be specifically targeted by using educational interventions, and research questions that still need answering specifically about the effectiveness of vitamin B12 for idiopathic fatigue.

In Switzerland, the human papillomavirus vaccination (HPVv) coverage rate lies below a desirable threshold. General practitioners (GPs) and pediatricians have been recognized as important providers of the HPVv, but there is little known about their self-attributed role and its relationship with their actual HPVv behavior. Therefore, the objective of this study was to explore the awareness, attitudes, and clinical practices of Swiss GPs and pediatricians concerning HPVv by means of a web-based questionnaire. We analyzed the responses of 422 physicians (72% GPs, 28% pediatricians). A substantial proportion of respondents considered the HPVv “absolutely essential” (54.2% of pediatricians, 30.6% of GPs). GPs indicated spending more time and effort on HPVv counseling for female rather than male patients more often compared to pediatricians (44.0% versus 13.9%, p < 0.001). The weekly number of patients aged 18–26 years seen in practice (p = 0.002) and whether the HPVv was deemed “absolutely essential” (adjusted odds ratio 2.39, 95% confidence interval 1.12–5.08) were factors associated with GPs administering HPVv in their practice. Shortcomings in terms of awareness, effort in the identification of potential vaccination candidates, and the role of male patients were revealed. By addressing these gaps, Swiss primary care providers could contribute to an increase in the national HPVv coverage rate.

In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected.Genes and Immunity (2005) 6, 66-69. doi:10.1038/sj.gene.6364146 Published online 11 November 2004 [ABSTRACT FROM AUTHOR]

Athletes competing in a wide variety of sports are at risk of contracting and spreading bacterial skin infections. Bacteria proliferate in environments of wet, macerated skin that is repeatedly abraded against competing athletes, equipment, clothing, or objects in the field of play. Common infections include impetigo, folliculitis, furunculosis, pitted keratolysis, and otitis externa. Diagnosis and treatment are often straightforward and vary little from care for nonathletes. However, knowledge of preventive strategies and return-to-play criteria, as outlined by the National Collegiate Athletic Association, are paramount for clinicians who care for competitive athletes. [ABSTRACT FROM AUTHOR]

Community-based research brings together researchers and community members as partners to conduct research of mutual concern. This article describes the components necessary to implement a successful research partnership, taking as an example a study of human immunodeficiency virus (HIV) risk among residents of senior housing sites in two North American cities. The article describes important aspects of building and sustaining partnerships, the methods implemented to conduct research on sensitive topics, share resources, disseminate results and collaborate on programs and interventions to benefit the health and well-being of older adults. [ABSTRACT FROM AUTHOR]

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.

Laboratory tests are frequently ordered by general practitioners (GPs), but little is known about time trends and between-GP variation of their use. In this retrospective longitudinal study, we analyzed over six million consultations by Swiss GPs during the decade 2009–2018. For 15 commonly used test types, we defined specific laboratory testing rates (sLTR) as the percentage of consultations involving corresponding laboratory testing requests. Patient age- and sex-adjusted time trends of sLTR were modeled with mixed-effect logistic regression accounting for clustering of patients within GPs. We quantified between-GP variation by means of intraclass correlation coefficients (ICC). Nine out of the 15 laboratory test types considered showed significant temporal increases, most eminently vitamin D (ten-year odds ratio (OR) 1.88, 95% confidence interval (CI) 1.71–2.06) and glycated hemoglobin (ten-year OR 1.87, 95% CI 1.82–1.92). Test types both subject to substantial increase and high between-GP variation of sLTR were vitamin D (ICC 0.075), glycated hemoglobin (ICC 0.101), C-reactive protein (ICC 0.202), and vitamin B12 (ICC 0.166). Increasing testing frequencies and large between-GP variation of specific test type use pointed at inconsistencies of medical practice and potential overuse.

Objective. This analysis describes the Outreach-Assisted Model of Partner Notification, an innovative strategy for encouraging seropositive injecting drug users (IDUs) to inform their partners of shared human immunodeficiency virus (HIV) exposure. The analysis focuses on two core components of the notification process: the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus. Methods. Using community outreach techniques, 386 IDUs were recruited for HIV pretest counseling, testing, and partner notification over a 12-month period. Of these, 63 tested HIV seropositive, and all but three returned for their test results. The 60 who were informed of their serostatus were randomly assigned to either a minimal or an enhanced intervention condition. Participants assigned to the minimal (self-tell) group were strongly encouraged to inform their partners of possible exposure. Those assigned to the enhanced (outreach-assisted) group had the option of either informing one or more of their partner(s) themselves or choosing to have the project's outreach team do so. Results. Together, the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years. By itself, drug use accounted for half of all partners named. Sexual behavior alone accounted for 25% of named partners. Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner; the team was requested to notify 71% of the total number of partners whom this group named. Conclusions. Findings suggest that IDUs want to notify their partners of shared HIV exposure. Outreach assistance was the preferred mode in the majority of cases. Expanding traditional communitybased HIV outreach activities to include delivering street-based counseling, testing, and partner notification appears to be a positive and workable prevention strategy. [ABSTRACT FROM AUTHOR]

Abstract Background During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. Methods From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. Results During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. Conclusion Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

Echocardiographic left ventricular (LV) hypertrophy was present in 120 of 160 patients (75%) (mean age 72 +/- 8 years) with systemic hypertension, coronary artery disease, and peripheral arterial disease (PAD) and in 43 of 94 age- and gender-matched patients (46%) with systemic hypertension, coronary artery disease, and no PAD (p<0.001). Echocardiographic LV hypertrophy was present in 63 of 68 patients with PAD (93%) with ankle-brachial indexes (ABIs) of <0.60 and in 57 of 92 patients (62%) with ABIs of 0.60 to 0.89 (p<0.001). [ABSTRACT FROM AUTHOR]

Objectives: Tajik male labour migrants who inject drugs while working in Moscow are at high risk of acquiring HIV and sexually transmitted infections (STIs) that compromise their health and potentially that of their sexual partners. In a cluster-randomized controlled trial, the "Migrants' Approached Self-Learning Intervention in HIV/AIDS for Tajiks" (MASLIHAT) reduced intervention participants' sexual risk behaviour including condomless sex, condomless sex with female sex workers (CS/FSW), and multiple sexual partners. This analysis investigates if the observed change in sexual risk behaviors due to the intervention translated into lower incidence of STIs among participants over 12-month follow-up., Methods: The MASLIHAT intervention was tested in a cluster-randomized controlled trial with sites assigned to either the MASLIHAT intervention or comparison health education training (TANSIHAT). Participants and network members (n=420) were interviewed at baseline and 3-month intervals for one year to assess HIV/STI sex and drug risk behaviour. Focusing solely on STIs in our current analysis, we conducted mixed effects robust Poisson regression analyses to test for differences between conditions in self-reported STIs during 12 months of follow-up, and to test the contribution of sexual risk behaviours to STI acquisition. Structural equation modelling investigated sexual behaviours as possibly mediating the observed differences in STI acquisition between the two conditions., Results: Participants in the MASLIHAT condition were significantly less likely to report an STI during follow-up (IRR=0.27, 95% CI 0.13-0.58). Of the 3 sexual risk behaviours of interest, only CS/FSW was significantly associated with STI acquisition (IRR=3.30, 95% CI 1.57-3.93). Adjusting for CS/FSW, the effect of MASLIHAT intervention participation was reduced (IRR=0.37, 95% CI 0.17-0.84), signalling possible mediation. Structural equation modelling indicated that the intervention's effect on STI incidence was mediated by reductions among MASLIHAT participants in CS/FSW., Conclusions: The MASLIHAT peer-education intervention reduced the incidence of STIs among Tajik labour migrants through reduced CS/FSW., Competing Interests: Competing interests The authors have no competing interests to declare.

Objective: We sought to describe patterns of and indications for surgical specialty consultation for facial laceration repair in pediatric emergency departments (PEDs)., Methods: We performed a multicenter survey of PED leadership throughout the United States and Canada evaluating the practice patterns of surgical specialty consultation for patients presenting for facial lacerations requiring repair. We measured demographics of PEDs, factors influencing the decision to obtain a surgical specialty consultation, and the presence and components of consultation guidelines. Factors related to consultation were ranked on a Likert scale from 1 to 5 (1 = Not at all important, 5 = Extremely important). We evaluated relationships between reported rates of surgical specialty consultation and PED region, annual PED volume, and reported factors associated with PED consultation., Results: Survey responses were received from 67/124 (54%) queried PEDs. The median self-reported rate of surgical specialty consultation for facial lacerations was 10% and ranged from 1% to 70%, with resident physicians performing the repair 71% of the time a subspecialist was consulted. There was regional variability in specialty consultation, with the highest and lowest rate in the Midwest and Canada, respectively ( P = 0.03). The top 4 influential factors prompting consultation with the highest percentage of responses of "Extremely Important" or "Very Important" were: discretion of the physician caring for the patient (95%), parental preference (39%), limited PED resources (32%), and patient requires sedation (32%). Surgical specialty consult guidelines were used in only 6% of PEDs with consensus that depth necessitating more than 2-layer repair or involvement of critical structures should prompt consultation., Conclusions: Surgical specialty usage in the management of patients who present with facial lacerations to PEDs has significant variation related to patient, provider, and department-level factors that influence the decision to consult. Lack of consult guidelines represent a potential opportunity to standardize care delivery to this common presentation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear., Aim: To explore clinical associations between DM characteristics and PD complications., Methods: We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45 years), average (45-65 years), and late (>65 years)., Outcomes: Outcomes included effects of DM characteristics on PD development, progression, and severity., Results: In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006)., Clinical Implications: These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges., Strengths and Limitations: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables., Conclusions: This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The "Migrants' Approached Self-Learning Intervention in HIV/AIDS for Tajiks" (MASLIHAT) recruits and trains Tajik labour migrants who inject drugs as peer educators (PEs) in delivering HIV prevention information and encouragement to adopt risk-reduction norms and practices within their diaspora social networks while reducing their own HIV risk., Methods: The MASLIHAT intervention was tested in Moscow in a cluster-randomized controlled trial with 12 recruitment sites assigned to either the MASLIHAT intervention or an equal-time peer-educator training focused on other health conditions (TANSIHAT). From October 2021 to April 2022, 140 male Tajik migrants who inject drugs were recruited as PEs to attend the 5-session MASLIHAT training or the TANSIHAT non-HIV comparison condition. Each participant in both groups recruited two network members (NMs) who inject drugs with the intent to share with them the information and positive strategies for change they had learned (n = 280). All PEs and NMs (n = 420) participated in baseline and follow-up interviews at 3-month intervals for 1 year. All received HIV counselling and testing. Modified mixed effects Poisson regressions tested for group differences in injection practices, sexual risk behaviours and heavy alcohol use over time., Results: At baseline, across both groups, 75% of participants reported receptive syringe sharing (RSS), 42% reported condomless sex and 20% reported binge drinking at least once a month. In contrast to TANSIHAT where HIV risk behaviours remained the same, significant intervention effects that were sustained over the 12 months were observed for receptive syringe and ancillary equipment sharing among both MASLIHAT PEs and NMs (p < 0.0001). Significant declines in the prevalence of sexual risk behaviours were also associated with the MASLIHAT intervention (p < 0.01), but not the comparison condition. Binge alcohol use was not affected in either condition; the MASLIHAT intervention had a transitory effect on drinking frequency that dissipated after 9 months., Conclusions: The MASLIHAT peer-education intervention proved highly effective in reducing HIV-related injection risk behaviour, and moderately effective in reducing sexual risk behaviour among both PEs and NMs. Network-based peer education is an important tool for HIV prevention among people who inject drugs, especially in environments that are not amenable to community-based harm reduction., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Objective: The aim of the study is to assess diagnostic performance of cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians in children with preexisting cardiac disease., Methods: We evaluated the use of cardiac POCUS performed by PEM physicians among a convenience sample of children with preexisting cardiac disease presenting to a tertiary care pediatric ED. We assessed patient characteristics and the indication for POCUS. The test characteristics of the sonologist interpretation for the assessment of both pericardial effusion as well as left ventricular systolic dysfunction were compared with expert POCUS review by PEM physicians with POCUS fellowship training., Results: A total of 104 children with preexisting cardiac disease underwent cardiac POCUS examinations between July 2015 and December 2017. Among children with preexisting cardiac disease, structural defects were present in 72%, acquired conditions in 22%, and arrhythmias in 13% of patients. Cardiac POCUS was most frequently obtained because of chest pain (55%), dyspnea (18%), tachycardia (17%), and syncope (10%). Cardiac POCUS interpretation compared with expert review had a sensitivity of 100% (95% confidence interval [CI], 85.7-100) for pericardial effusion and 100% (95% CI, 71.5-100) for left ventricular systolic dysfunction; specificity was 97.5% (95% CI, 91.3.1-99.7) for pericardial effusion and 98.9% (95% CI, 93.8-99.8) for left ventricular systolic dysfunction., Conclusions: Cardiac POCUS demonstrates good sensitivity and specificity in diagnosing pericardial effusion and left ventricular systolic dysfunction in children with preexisting cardiac conditions when technically adequate studies are obtained. These findings support future studies of cardiac POCUS in children with preexisting cardiac conditions presenting to the ED., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hydrogen sulfide (H 2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H 2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H 2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H 2 S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H 2 S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H 2 S concentration ranging from 0.21 to 4.5 ppm (R 2 = 0.954) with a normalized sensitivity of 12.4% ppm -1 when evaluated in a benchtop setting. The sensor proves highly selective toward H 2 S in the presence of known interferent gases, such as hydrogen (H 2 ), with a selectivity ratio of H 2 S:H 2 = 1340, as well as toward methane (CH 4 ) and carbon dioxide (CO 2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H 2 S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H 2 S., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

This single-center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40-min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUC inf values of MIJ821 increased in a dose-proportional manner across the dose range 0.016-0.48 mg/kg and the C max values in a slight overproportional manner across the dose range 0.048-0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUC inf was 708 h ng/mL and the geometric mean C max was 462 ng/mL. Inspection of 1-h post-dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose-dependent., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Surgical treatment for insertional Achilles tendinosis (IAT) sometimes requires tendon repair augmentation. The purpose of this study is to evaluate the efficacy of polycaprolactone-based polyurethane urea (PUUR) matrix augmentation in the treatment of IAT., Methods: A retrospective review was performed in surgically treated IAT. Repairs were augmented with a PUUR matrix. Factors evaluated included date of full weightbearing, patient satisfaction, Visual Analog Scale (VAS) pain score, strength, and ankle motion. The Wilcoxon signed-rank test was used to compare baseline and final follow-up VAS scores., Results: A total of 18 cases were included in the study. The mean patient age was 54.61 ± 8.25 (40-75) years with a mean follow-up of 163.61 ± 57.81 (92-314) days. Patient satisfaction was obtained on 15 of 18 patients, with 14 patients satisfied with their outcome. Mean VAS for pain significantly decreased from 6.19 ± 1.97 (2.5-9) to 0.83 ± 1.54 (0-5) postoperatively, which was statistically significant (P < .01)., Conclusion: Achilles tendon augmentation with the PUUR matrix is a viable option in the treatment of IAT. Its use in this condition has minimal morbidity and can be an alternative to other forms of augmentation., Levels of Evidence: Level IV: Retrospective case series.

Introduction: Assisted partner notification (APN) safely and effectively increases partner awareness of HIV exposure, testing and case identification in community settings. Nonetheless, it has not been specifically developed or evaluated for use in prison settings where people with HIV often are diagnosed and may have difficulty contacting or otherwise notifying partners. We developed Impart, a prison-based APN model, and evaluated its efficacy in Indonesia to increase partner notification and HIV testing., Methods: From January 2020 to January 2021, 55 incarcerated men with HIV were recruited as index participants from six jail and prison facilities in Jakarta in a two-group randomized trial comparing the outcomes of self-tell notification (treatment as usual) versus Impart APN in increasing partner notification and HIV testing. Participants voluntarily provided names and contact information for sex and drug-injection partners in the community with whom they had shared possible HIV exposure during the year prior to incarceration. Participants randomized to the self-tell only condition were coached in how to notify their partners by phone, mail or during an in-person visit within 6 weeks. Participants randomized to Impart APN could choose between self-tell notification or anonymous APN by a two-person team consisting of a nurse and outreach worker. We compared the proportion of partners in each group who were notified of exposure by the end of 6 weeks, subsequently tested and HIV diagnosed., Results: Index participants (n = 55) selected 117 partners for notification. Compared to self-tell notification, Impart APN resulted in nearly a six-fold increase in the odds of a named partner being notified of HIV exposure. Nearly two thirds of the partners notified through Impart APN (15/24) completed HIV testing within 6 weeks post notification compared to none of those whom participants had self-notified. One-third of the partners (5/15) who completed HIV testing post notification were diagnosed as HIV positive for the first time., Conclusions: Voluntary APN can be successfully implemented with a prison population and within a prison setting despite the many barriers to HIV notification that incarceration presents. Our findings suggest that the Impart model holds considerable promise to increase partner notification, HIV testing and diagnosis among sex and drug-injecting partners of HIV-positive incarcerated men., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

The human immunodeficiency virus (HIV) epidemic in Eastern Europe and Central Asia continues to grow with most infections occurring in high-risk groups including people who inject drugs and their sexual partners. Labor migrants from this region who inject drugs while in Russia are at especially high HIV risk. Male Tajik migrant workers who inject drugs in Moscow (N = 420) were interviewed prior to a randomized trial of the Migrants' Approached Self-Learning Intervention in HIV/AIDS (MASLIHAT) peer-education HIV-prevention intervention. Participants were interviewed about their sex and drug use behavior and tested for HIV and hepatitis C (HCV) prior to the intervention. Only 17% had ever been tested for HIV. Over half of the men reported injecting with a previously used syringe in the past month, and substantial proportions reported risky sexual behavior. Prevalence rates of HIV (6.8%) and HCV (2.9%) were elevated, although lower than expected when compared to estimates of prevalence among people who inject drugs at the national level in Tajikistan. Risk behavior in diaspora varied across the men's regional area of origin in Tajikistan and occupation in Moscow, with HIV prevalence rates highest among those working at the bazaars. Evidence-based prevention approaches and messaging that specifically address the drug- and sex-related risk behavior of migrants with varying backgrounds are needed.

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit ® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

The artificial urinary sphincter (AUS) is the "gold standard" surgical treatment for severe stress urinary incontinence.  However, a subset of patients with frail urethras may require technical adjuncts to ensure optimal cuff function.  Our objective is to provide a detailed tutorial of our institution's method for performing urethral bulking with native tissue in patients with frail urethras during AUS surgery. We have found that urethral bulking with native tissue provides a cost-efficient and durable technique for improved AUS cuff coaptation.  Our experience demonstrates adequate short and intermediate term efficacy with limited complications.  These techniques equip surgeons with an alternative surgical approach for appropriate patients receiving AUS surgery who have been previously exposed to pelvic radiation and/or significant surgical morbidity resulting in frail urethral tissue.

Background: Assisted partner notification (APN) is recommended as a public health strategy to increase HIV testing in people exposed to HIV. Yet its adoption in many countries remains at an early stage. This qualitative study sought the opinions of HIV health service providers regarding the appropriateness and feasibility of implementing APN in Indonesia where such services are on the cusp of adoption., Methods: Four focus group discussions totaling 40 health service providers were held in Jakarta, Indonesia to consider APN as an innovative concept and to share their reactions regarding its potential implementation in Indonesia. Voice-recorded discussions were conducted in Bahasa, transcribed verbatim, and analyzed., Results: Participants recognized APN's potential in contacting and informing the partners of HIV-positive clients of possible viral exposure. They also perceived APN's value as a client-driven service permitting clients to select which of three partner notification methods would work best for them across differing partner relationships and settings. Nonetheless, participants also identified personal and health system challenges that could impede successful APN adoption including medical and human resource limitations, the need for specialized APN training, ethical and equity considerations, and lack of sufficient clarity concerning laws and government policies regulating 3 rd party disclosures. They also pointed to the job-overload, stress, personal discomfort, and the ethical uncertainty that providers might experience in delivering APN., Conclusion: Overall, providers of HIV services embraced the concept of APN but forecast practical difficulties in key service areas where investments in resources and system change appeared necessary to ensure effective and equitable implementation., (© 2023. The Author(s).)

Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major ischemic priapism. Treatment of acute ischemic priapism is reactive; whereas ideal management consists of preventative approaches to ultimately promote the best improvement in patient's quality of life. Leg ulcers in patients with sickle cell disease (SCD) are quite common, with ∼20 % of patients with HBSS reporting either having an active or a past ucler. They can be confused with venous ulcers, with lower extremity hyperpigmentation confounding further the diagnosis. Several factors believed to contribute to the development of leg ulcers in patients with SCD are discussed in this article. Sickle cell liver disease (SCLD) occurs because of a wide variety of insults to the liver that happen during the lifetime of these patients. SCLD includes a range of complications of the hepatobiliary system and is increasing in prevalence with the aging adult sickle population. Liver nodular regenerative hyperplasia (NRH) is more common than realized and underappreciated as a diagnosis and requires liver biopsy with reticulin staining. Undiagnosed, the insidious damage from liver NRH can lead to noncirrhotic portal hypertension or cirrhosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Intimate partner violence (IPV) in China is a largely understudied, major health risk among women living with HIV. Using structured face-to-face interviews, this research examined partner and couple relationship characteristics associated with physical and sexual IPV among 219 HIV-positive women living with a male partner in Ruili, China. Twenty-nine women (13%) reported past-year occurrences of physical IPV, and 24 (11%) reported sexual IPV. Physical IPV was more common when the woman's partner was of Jingpo ethnicity, drank weekly, or learned of her HIV status indirectly from a third person. Reduced risk of physical IPV was associated with a woman's perceived confidant support that was available through either her partner or a minimum of 2 non-partner confidants. Sexual IPV was more often reported among women with a partner who drank frequently or was concurrently HIV-positive, or in situations where the woman was employed and the partner was not. Sexual IPV was less likely with a partner of Dai ethnicity than Han, the major ethnicity in China. Identifying determinants of IPV vulnerability among women living with HIV may help future interventions to achieve greater impact in similar settings., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)