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IntroductionThe use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region.MethodsA cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed.ResultsCognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3-98.7) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively.ConclusionFindings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.

BackgroundIn absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB-IRIS outside the central nervous system remains unclear. However, this guideline change was not based on conclusive evidence, and it remains unclear whether SDI of ART or TB test results should be prioritized in people with HIV (PWH) and presumptive TB.Design and methodsSaDAPT is an open-label, pragmatic, parallel, 1:1 individually randomized, non-inferiority trial comparing two strategies for the timing of ART initiation in PWH with presumptive TB ("ART first" versus "TB results first"). PWH in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one TB symptom (cough, fever, night sweats or weight loss) and no signs of intracranial infection are eligible. After a baseline assessment, participants in the "ART first" arm will be offered SDI of ART, while those in the "TB results first" arm will be offered ART only after active TB has been confirmed or refuted. We hypothesize that the "ART first" approach is safe and non-inferior to the "TB results first" approach with regard to HIV viral suppression (Expected outcomesSaDAPT will provide evidence on the safety and effects of SDI of ART in PWH with presumptive TB in a pragmatic clinical trial setting.Trial registrationThe trial has been registered on clinicaltrials.gov (NCT05452616; July 11 2022).

Abstract Introduction Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. Methods In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL

Objectives This scoping review aims to identify and synthesise existing statistical methods used to assess the progress of HIV treatment programmes in terms of the HIV cascade and continuum of care among people living with HIV (PLHIV).Design Systematic scoping review.Data sources Published articles were retrieved from PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete and Excerpta Medica dataBASE (EMBASE) databases between April and July 2022. We also strategically search using the Google Scholar search engine and reference lists of published articles.Eligibility criteria This scoping review included original English articles that estimated and described the HIV cascade and continuum of care progress in PLHIV. The review considered quantitative articles that evaluated either HIV care cascade progress in terms of the Joint United Nations Programme on HIV and AIDS targets or the dynamics of engagement in HIV care.Data extraction and synthesis The first author and the librarian developed database search queries and screened the retrieved titles and abstracts. Two independent reviewers and the first author extracted data using a standardised data extraction tool. The data analysis was descriptive and the findings are presented in tables and visuals.Results This review included 300 articles. Cross-sectional study design methods were the most commonly used to assess the HIV care cascade (n=279, 93%). In cross-sectional and longitudinal studies, the majority used proportions to describe individuals at each cascade stage (276/279 (99%) and 20/21 (95%), respectively). In longitudinal studies, the time spent in cascade stages, transition probabilities and cumulative incidence functions was estimated. The logistic regression model was common in both cross-sectional (101/279, 36%) and longitudinal studies (7/21, 33%). Of the 21 articles that used a longitudinal design, six articles used multistate models, which included non-parametric, parametric, continuous-time, time-homogeneous and discrete-time multistate Markov models.Conclusions Most literature on the HIV cascade and continuum of care arises from cross-sectional studies. The use of longitudinal study design methods in the HIV cascade is growing because such methods can provide additional information about transition dynamics along the cascade. Therefore, a methodological guide for applying different types of longitudinal design methods to the HIV continuum of care assessments is warranted.

Introduction. Sub-Saharan Africa is home to 89% of all young people living with HIV, a key population with specific challenges and needs. In-depth knowledge of service demands is needed to tailor and differentiate service delivery for this group. We evaluated HIV care preferences among young people living with HIV who were part of the PEBRA (Peer Educator Based Refill of ART) cluster-randomized trial. Methods. The PEBRA trial evaluated a novel model of care at 20 health facilities in Lesotho, Southern Africa. In the PEBRA model, a peer educator regularly assessed participant preferences regarding antiretroviral therapy (ART) refill location, SMS notifications (for adherence, drug refill, viral load), and general care support options and delivered services accordingly over a 12-month period. We present these preferences and their changes over time. Results. At enrolment, 41 of 123 (33.3%) chose ART refill outside the health facility, compared to 8 of 123 (6.5%) after 12 months. Among those selecting clinic-based ART refill, many preferred collecting ART during the peer educator led Saturday clinic club, 45 of 123 (36.5%) at the beginning and 55 of 123 (44.7%) at the end. SMS reminders for treatment adherence and ART refill visits were chosen by 51 of 123 (41.5%) at enrolment and 54 of 123 (44.7%) at the last assessment. Support by the peer educator was popular at the beginning (110 of 123 (89.4%)) and lower but still high at the end (85 of 123 (69.1%)). Thirteen of 123 (10.6%) participants chose support by the nurse, without the involvement of any peer educator, at the first and 21 of 123 (17.1%) at the last assessment. Conclusion. Our longitudinal preference assessment among young people living with HIV in Lesotho showed a sustained interest in SMS notifications for adherence and refill visits as well as in additional support by a peer educator. ART refill outside the health facility was not as popular as expected; instead, medication pick-up at the facility, especially during Saturday clinic clubs, was favoured. The PEBRA trial was registered with clinicaltrials.gov (NCT03969030. Registered on 31 May 2019)

BackgroundSouthern and Eastern Africa is home to more than 2.1 million young people aged 15 to 24 years living with HIV. As compared with other age groups, this population group has poorer outcomes along the HIV care cascade. Young people living with HIV and the research team co-created the PEBRA (Peer Educator-Based Refill of ART) care model. In PEBRA, a peer educator (PE) delivered services as per regularly assessed patient preferences for medication pick-up, short message service (SMS) notifications, and psychosocial support. The cluster-randomized trial compared PEBRA model versus standard clinic care (no PE and ART refill done by nurses) in 3 districts in Lesotho.Methods and findingsIndividuals taking antiretroviral therapy (ART) aged 15 to 24 years at 20 clinics (clusters) were eligible. In the 10 clinics randomized to the intervention arm, participants were offered the PEBRA model, coordinated by a trained PE and supported by an eHealth application (PEBRApp). In the 10 control clusters, participants received standard nurse-coordinated care without any service coordination by a PE. The primary endpoint was 12-month viral suppression below 20 copies/mL. Analyses were intention-to-treat and adjusted for sex. From November 6, 2019 to February 4, 2020, we enrolled 307 individuals (150 intervention, 157 control; 218 [71%] female, median age 19 years [interquartile range, IQR, 17 to 22]). At 12 months, 99 of 150 (66%) participants in the intervention versus 95 of 157 (61%) participants in the control arm had viral suppression (adjusted odds ratio (OR) 1.27; 95% confidence interval [CI] [0.79 to 2.03]; p = 0.327); 4 of 150 (2.7%) versus 1 of 157 (0.6%) had died (adjusted OR 4.12; 95% CI [0.45 to 37.62]; p = 0.210); and 12 of 150 (8%) versus 23 of 157 (14.7%) had transferred out (adjusted OR 0.53; 95% CI [0.25 to 1.13]; p = 0.099). There were no significant differences between arms in other secondary outcomes. Twenty participants (11 in intervention and 9 in control) were lost to follow-up over the entire study period. The main limitation was that the data collectors in the control clusters were also young peers; however, they used a restricted version of the PEBRApp to collect data and thus were not able to provide the PEBRA model. The trial was prospectively registered on ClinicalTrials.gov (NCT03969030).ConclusionsPreference-based peer-coordinated care for young people living with HIV, compared to nurse-based care only, did not lead to conclusive evidence for an effect on viral suppression.Trial registrationclinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030.

Abstract Background The spread of the COVID-19 pandemic throughout the world presents an unprecedented challenge to public health inequities. People who use opioids may be a vulnerable group disproportionately impacted by the current pandemic, however, the limited prior research in this area makes it unclear whether COVID-19 and opioid use outcomes may be related, and whether other environmental and socioeconomic factors might play a role in explaining COVID-19 mortality. The objective of this study is to evaluate the association between opioid-related mortality and COVID-19 mortality across U.S. counties. Methods Data from 3142 counties across the U.S. were used to model the cumulative count of deaths due to COVID-19 up to June 2, 2020. A multivariable negative-binomial regression model was employed to evaluate the adjusted COVID-19 mortality rate ratios (aMRR). Results After controlling for covariates, counties with higher rates of opioid-related mortality per 100,000 persons were found to be significantly associated with higher rates of COVID-19 mortality (aMRR: 1.0134; 95% CI [1.0054, 1.0214]; P = 0.001). Counties with higher average daily Particulate Matter (PM2.5) exposure also saw significantly higher rates of COVID-19 mortality. Analyses revealed rural counties, counties with higher percentages of non-Hispanic whites, and counties with increased average maximum temperatures are significantly associated with lower mortality rates from COVID-19. Conclusions This study indicates need for public health efforts in hard hit COVID-19 regions to also focus prevention efforts on overdose risk among people who use opioids. Future studies using individual-level data are needed to allow for detailed inferences.

Abstract Background Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa. Methods In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged

Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by exposure to alcohol in utero. It has pervasive, lifelong impacts and is recognised as a major public health concern in many countries where alcohol is used. The FASD Research Australia Centre of Research Excellence (CRE) was funded by the National Health and Medical Research Council to generate and translate evidence to address prevention, diagnosis, and management of FASD in Australia. The current paper describes the approach to policy and practice impact taken by our CRE, including our stakeholder engagement processes and the key principles that underlie our approach. We provide examples of policy and practice influence in FASD prevention, diagnosis and management that have been achieved over the past five years and discuss challenges that are routinely faced in the translation of our work.

Abstract Background Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). Methods GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to

Abstract Background Despite tremendous progress in controlling the HIV epidemic in sub-Saharan Africa, HIV-related mortality continues to increase among adolescents and young people living with HIV (AYPLHIV). Globally, sub-Saharan Africa accounts for 85% of the AYPLHIV. Overall outcomes along the HIV care cascade are worse among AYPLHIV as compared to all other age groups due to various challenges in accessing and adhering to antiretroviral therapy (ART). New, innovative multicomponent packages of differentiated service delivery (DSD) models, are required to address the specific needs of AYPLHIV. This study aims to evaluate the feasibility and effectiveness of a multicomponent DSD model (PEBRA model) designed for AYPLHIV and coordinated by a peer-educator. Methods PEBRA (Peer-Educator Based Refill of ART) is a cluster randomized, open-label, superiority trial conducted at 20 health facilities in three districts of Lesotho, Southern Africa. The clusters (health facilities) are randomly assigned to either the PEBRA model or standard of care in a 1:1 ratio, stratified by district. AYPLHIV aged 15–24 years old in care and on ART at one of the clusters are eligible. In the PEBRA model, a peer-educator coordinates the antiretroviral therapy (ART) services - such as medication pick-up, SMS notifications and support options - according to the preferences of the AYPLHIV. The peer-educator delivers this personalized model using a tablet-based application called PEBRApp. The control clusters continue to offer standard of care: ART services coordinated by the nurse. The primary endpoint is viral suppression at 12 months. Secondary endpoints include self-reported adherence to ART, quality of life, satisfaction with care and engagement in care. The target sample size is 300 AYPLHIV. Statistical analyses are conducted and reported in line with CONSORT guidelines for cluster randomized trials. Discussion The PEBRA trial will provide evidence on the feasibility and effectiveness of an inclusive, holistic and preference-based DSD model for AYPLHIV that is coordinated by a peer-educator. Many countries in SSA have an existing peer-educator program. If proven effective, the PEBRA model and PEBRApp have the potential to be scaled up to similar settings. Trial registration Clinicaltrials.gov , NCT03969030 . Registered on 31 May 2019. More information: www.pebra.info

Aboriginal and Torres Strait Islander young people are over-represented in Australian youth detention centres and the justice system. In contrast to deficit-focused approaches to health and justice research, this article engages with the hopes, relationships and educational experiences of 38 detained youth in Western Australia who participated in a study of screening and diagnosis for fetal alcohol spectrum disorder. We report on a qualitative study that used a ‘social yarning’ approach. While the participants reported lives marred by substance use, crime, trauma and neurodevelopmental disability, they also spoke of strong connections to country and community, their education experiences and their future goals. In line with new efforts for a ‘positive youth justice’ and extending on models of recovery capital, we argue that we must celebrate success and hope through a process of mapping and building recovery capital in the justice context at an individual and institutional level.

BackgroundCommunity-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation.Methods and findingsThe VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30-48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference -0.07 [95% CI -0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [-0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference -0.12 [-0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population.ConclusionsThe offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community.Trial registrationRegistered with Clinicaltrials.gov (NCT03630549).

Introduction: In the HOSENG trial (NCT03598686), the secondary distribution of oral self-tests for persons absent or refusing to test during a home-based HIV testing campaign in rural Lesotho resulted in an increase in testing coverage of 21% compared to a testing campaign without secondary distribution. This study aims to determine the per patient costs of both HOSENG trial arms.Method: We conducted a micro-costing study to estimate the cost of home-based HIV testing with (HOSENG intervention arm) and without (HOSENG control arm) secondary self-test distribution from a provider's perspective. A mixture of top-down and bottom-up costing was used. We estimated both the financial and economic per patient costs of each possible testing cascade scenario. The costs were adjusted to 2018 US$.Results: The overall provider cost for delivering the home-based HIV testing with secondary distribution was US$36,481 among the 4,174 persons enumerated and 3,094 eligible for testing in the intervention villages compared to US$28,620 for 3,642 persons enumerated and 2,727 eligible for testing in the control. The cost per person eligible for testing was US$11.79 in the intervention vs. US$10.50 in the control. This difference was mainly driven by the cost of distributed oral self-tests. The cost per person tested was, however, lower in intervention villages (US$15.70 vs. US$22.15) due to the higher testing coverage achieved through self-test distribution. The cost per person confirmed new HIV+ was US$889.79 in the intervention and US$753.17 in the control.Conclusion: During home-based HIV testing in Lesotho, the secondary distribution of self-tests for persons absent or refusing to test during the visit reduced the costs per person tested and thus presents a promising add-on for such campaigns.Trial Registration:https://ClinicalTrials.gov/, identifier: NCT03598686

Abstract Background Home-based HIV testing and counselling (HB-HTC) is frequently used to increase awareness of HIV status in sub-Saharan Africa. Whereas acceptance of HB-HTC is usually high, testing coverage may remain low due to household members being absent during the home visits. This study assessed whether two consecutive visits, one during the week, one on the weekend, increase coverage. Methods The study was a predefined nested-study of the CASCADE-trial protocol and conducted in 62 randomly selected villages and 17 urban areas in Butha-Buthe district, Lesotho. HB-HTC teams visited each village/urban area twice: first during a weekday, followed by a weekend visit to catch-up for household members absent during the week. Primary outcome was HTC coverage after first and second visit. Coverage was defined as all individuals who knew their HIV status out of all household members (present and absent). Results HB-HTC teams visited 6665 households with 18,286 household members. At first visit, 69.2 and 75.4% of household members were encountered in rural and urban households respectively (p

Abstract Background There is a need for evaluating community-based antiretroviral therapy (ART) delivery models to improve overall performance of HIV programs, specifically in populations that may have difficulties to access continuous care. This cluster-randomized clinical trial aims to evaluate the effectiveness of a multicomponent differentiated ART delivery model (VIBRA model) after home-based same-day ART initiation in remote villages in Lesotho, southern Africa. Methods/design The VIBRA trial (VIllage-Based Refill of ART) is a cluster-randomized parallel-group superiority clinical trial conducted in two districts in Lesotho, southern Africa. Clusters (i.e., villages) are randomly assigned to either the VIBRA model or standard care. The clusters are stratified by district, village size, and village access to the nearest health facility. Eligible individuals (HIV-positive, aged 10 years or older, and not taking ART) identified during community-based HIV testing campaigns are offered same-day home-based ART initiation. The intervention clusters offer a differentiated ART delivery package with two features: (1) drug refills and follow-ups by trained and supervised village health workers (VHWs) and (2) the option of receiving individually tailored adherence reminders and notifications of viral load results via SMS. The control clusters will continue to receive standard care, i.e., collecting ART refills from a clinic and no SMS notifications. The primary endpoint is viral suppression 12 months after enrolment. Secondary endpoints include linkage to and engagement in care. Furthermore, safety and cost-effectiveness analyses plus qualitative research are planned. The minimum target sample size is 262 participants. The statistical analyses will follow the CONSORT guidelines. The VIBRA trial is linked to another trial, the HOSENG (HOme-based SElf-testiNG) trial, both of which are within the GET ON (GETing tOwards Ninety) research project. Discussion The VIBRA trial is among the first to evaluate the delivery of ART by VHWs immediately after ART initiation. It assesses the entire HIV care cascade from testing to viral suppression. As most countries in sub-Saharan Africa have cadres like the VHW program in Lesotho, this model—if shown to be effective—has the potential to be scaled up. The system impact evaluation will provide valuable cost estimations, and the qualitative research will suggest how the model could be further modified to optimize its impact. Trial registration Clinicaltrials.gov, NCT03630549. Registered on 15 August 2018.

Abstract Background HIV-testing coverage remains below the targeted 90% despite efforts and resources invested. Home-based HIV-testing is a key approach endorsed by the World Health Organization (WHO), especially to reach individuals who might not seek testing otherwise. Although acceptance of testing during such campaigns is high, coverage remains low due to absent household members. This cluster-randomized trial aims to assess increase in testing coverage using oral HIV self-testing (HIVST) among individuals who are absent or decline testing during home-based HIV-testing. Methods The HOSENG (HOme-based SElf-testiNG) trial is a cluster-randomized, parallel-group, superiority trial in two districts of Lesotho, Southern Africa. Clusters are stratified by district, village size, and village access to the nearest health facility. Cluster eligibility criteria include: village is in catchment area of one of the study facilities, village authority provides consent, and village has a registered, capable, and consenting village health worker (VHW). In intervention clusters, HIV self-tests are provided for eligible household members who are absent or decline HIV-testing in the presence of the campaign team. In control clusters, standard of care for absent and refusing individuals applies, i.e., referral to a health facility. The primary outcome is HIV-testing coverage among individuals aged 12 years or older within 120 days after enrollment. Secondary objectives include HIV-testing coverage among other age groups, and uptake of the different testing modalities. Statistical analyses will be conducted and reported in line with CONSORT guidelines. The HOSENG trial is linked to the VIBRA (Village-Based Refill of ART) trial. Together, they constitute the GET ON (GETting tOwards Ninety) research project. Discussion The HOSENG trial tests whether oral HIVST may be an add-on during door-to-door testing campaigns towards achieving optimal testing coverage. The provision of oral self-test kits, followed up by VHWs, requires little additional human resources, finances and logistics. If cost-effective, this approach should inform home-based HIV-testing policies not only in Lesotho, but in similar high-prevalence settings. Trial registration ClinicalTrials.gov, (ID: NCT03598686). Registered on 25 July 2018. More information is available at www.getonproject.wordpress.com.

The author discusses the 2010 Affordable Care Act in the U.S. by comparing it with the National Health Service in the United Kingdom, where is both the payer and provider of health care, and in France, where health coverage is universal and compulsory. The U.S. health care system fails in basic dimensions–like preventative care and reimbursement schemes for physicians–but its innovation, technology, and research enable many people to live longer and healthier lives. Moreover, in the U.S., regulation of the pharmaceutical industry and of drug prices should be reformed, but the political scene and market dynamics make any attempt to reform a currently impossible task.

ObjectiveRitonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa.MethodsUsing data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate ResultsRenal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) ConclusionsIn PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

BackgroundCurrent World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment.Methods and findingsThis multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100-999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (ConclusionsIn this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines.Trial registrationThe trial is registered at ClinicalTrials.gov, NCT03088241.

Introduction Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). FASD research is a rapidly growing field that crosses multiple disciplines. To ensure research is relevant and meaningful for people living with FASD, their families, and the broader public there is a need to engage community members in setting priorities for research. Objectives Our primary objective was to formally identify the views of people living with FASD, their par- ents/caregivers, service providers, and the general community on the research priorities for FASD and alcohol use in pregnancy in Australia. Our secondary objective was to provide an overview of current research in the highest priority areas identified. Methods The approach for this study involved two community surveys and a consensus workshop, followed by a rapid literature review. Survey responses (n = 146) were collected and grouped using qualitative thematic analysis. The themes identified were then ranked in a second survey (n = 45). The 22 highest ranked themes were considered in a workshop with 21 community members, and consensus on the top ten priority areas was sought. The priority areas were grouped into conceptually similar topics and rapid literature reviews were undertaken on each. Results A diverse range of priorities was identified within key areas of prevention, diagnosis, and therapy. On request from participants, separate priority lists were developed by Aboriginal and non-Aboriginal participants. Conclusions There is need for a national network of researchers to take forward the research commenced by the Centre of Research Excellence, FASD Research Australia, in addressing community priorities.

BACKGROUND:In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS:We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS:We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/μl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p

Abstract Background The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. Methods In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL

IntroductionFor HIV-positive individuals on antiretroviral therapy (ART), the World Health Organization (WHO) recommends routine viral load (VL) monitoring. We report on the cascade of care in individuals with unsuppressed VL after introduction of routine VL monitoring in a district in Lesotho.Materials and methodsIn Butha-Buthe district 12 clinics (11 rural, 1 hospital) send samples for VL testing to the district laboratory. We included data from patients aged ≥15 years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL ResultsFor 9,949 individuals 24,948 VL tests were available. The majority were female (73%), median age 41 years (interquartile range 33-52), and 58% seen at rural clinics. Overall, 25% (260/1028) of individuals were managed according to guidelines: 40% (410/1028) had a follow-up VL within 180 days of their initial unsuppressed VL and 25% (260/1028) of those either re-suppressed or switched to second-line within 90 days. Female patients were more likely to have a follow-up VL done, (p = 0.015). In rural clinics rates of two consecutively unsuppressed VLs were higher than in the hospital (64% vs. 44%, pConclusionsOur data show that in a real-life setting availability of routine VL monitoring may not be exploited to its potential. A lack of timely follow-up after a first unsuppressed VL and reluctance to switch patients with confirmed virological failure, reduce the benefit of VL monitoring, i.e. in the rural clinics. Future studies will have to assess models of care which ensure that VL results are met with an action and make use of scalable innovative approaches.

Abstract Background Achievement of the UNAIDS 90-90-90 targets in Sub-Sahara Africa is challenged by a weak care-cascade with poor linkage to care and retention in care. Community-based HIV testing and counselling (HTC) is widely used in African countries. However, rates of linkage to care and initiation of antiretroviral therapy (ART) in individuals who tested HIV-positive are often very low. A frequently cited reason for non-linkage to care is the time-consuming pre-ART assessment often requiring several clinic visits before ART-initiation. Methods This two-armed open-label randomized controlled trial compares in individuals tested HIV-positive during community-based HTC the proposition of same-day community-based ART-initiation to the standard of care pre-ART assessment at the clinic. Home-based HTC campaigns will be conducted in catchment areas of six clinics in rural Lesotho. Households where at least one individual tested HIV positive will be randomized. In the standard of care group individuals receive post-test counselling and referral to the nearest clinic for pre-ART assessment and counselling. Once they have started ART the follow-up schedule foresees monthly clinic visits. Individuals randomized to the intervention group receive on the spot point-of-care pre-ART assessment and adherence counselling with the proposition to start ART that same day. Once they have started ART, follow-up clinic visits will be less frequent. First primary outcome is linkage to care (individual presents at the clinic at least once within 3 months after the HIV test). The second primary outcome is viral suppression 12 months after enrolment in the study. We plan to enrol a minimum of 260 households with 1:1 allocation and parallel assignment into both arms. Discussion This trial will show if in individuals tested HIV-positive during community-based HTC campaigns the proposition of same-day ART initiation in the community, combined with less frequent follow-up visits at the clinic could be a pragmatic approach to improve the care cascade in similar settings. Trial registration NCT02692027 , registered February 21, 2016

Context: Atherosclerosis, the underlying cause of coronary heart disease, has been shown to be present even in young adults.Objective: To document the extent and severity of atherosclerosis in adolescents and young adults in the United States.Design and Setting: The Pathobiological Determinants of Atherosclerosis in Youth Study, a multi-institutional autopsy study conducted in US medical centers. Subjects A total of 2876 study subjects, between 15 and 34 years old, black and white, men and women, who died of external causes and underwent autopsy between June 1, 1987, and August 31, 1994.Main Outcome Measures: Extent, prevalence, and topography of atherosclerotic lesions.Results: Intimal lesions appeared in all the aortas and more than half of the right coronary arteries of the youngest age group (15-19 years) and increased in prevalence and extent with age through the oldest age group (30-34 years). Fatty streaks were more extensive in black subjects than in white subjects, but raised lesions did not differ between blacks and whites. Raised lesions in the aortas of women and men were similar, but raised lesions in the right coronary arteries of women were less than those of men. The prevalence of total lesions was lower in the right coronary artery than in the aorta, but the proportion of raised lesions among total lesions was higher in the right coronary artery than in the aorta.Conclusions: Atherosclerosis begins in youth. Fatty streaks and clinically significant raised lesions increase rapidly in prevalence and extent during the 15- to 34-year age span. Primary prevention of atherosclerosis, as contrasted with primary prevention of clinically manifest atherosclerotic disease, must begin in childhood or adolescence. [ABSTRACT FROM AUTHOR]

As the interlobular arteries of the ageing kidney progressively accumulate intimal fibroplasia, these fibroplastic changes appear to introduce strictures upon the interlobular arteries. These strictures are expected to generate nephron heterogeneity, which is a uniquely disturbed setting peculiarly suited to sustaining both high and low renin forms of hypertension. Fibroplastic renovasculopathy accumulates with age at varying rates in different human populations, and these rates closely parallel the rise of blood pressure with age, as documented by community surveys. Here, I introduce the expression type 1 for hypertension in subjects with mild or minimal renovasculopathy, and type 2 for those with severe vasculopathy. Data reviewed here simply that variations in prevailing blood pressure levels between populations can be attributed entirely, or almost entirely, to type 2 hypertension. No practical test is available to detect nephron heterogeneity clinically. Tests for this purpose have not been and are not now in development. The reason for this deficiency is probably the general lack of suspicion regarding the existence of this pathological entity. Once the entity becomes the target of attention, a variety of tests for measuring its severity in clinical patients should follow readily. [ABSTRACT FROM PUBLISHER]

Tobacco smoking during pregnancy contributes to a range of adverse perinatal outcomes; but is a potentially modifiable behavior. In Australia Aboriginal and Torres Strait Islander women face a range of barriers that hinder; rather than support smoking cessation. Few smoking cessation programs consider the broader social determinants of women’s lives; the gendered nature of these or the complexities which impinge on behavior change in the presence of social and economic disadvantage and substantial individual and intergenerational trauma. Drawing on the salient gender and trauma-informed literature this paper describes the rationale underpinning formative research which will inform the design of a localized, culturally meaningful smoking cessation program for Aboriginal women living in the Hedland and Western Desert communities of the remote Pilbara region of Western Australia. We contend that a women-centered, trauma-informed approach to smoking cessation has much to offer those seeking to address this critical public health issue

Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on the presence of the active site serine for Adiponutrin, Desnutrin/ATGL, and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like, but not Adiponutrin, decreases intracellular triglyceride levels. This is consistent with a function for Desnutrin/ATGL, GS2, and GS2-Like in lipolysis, but not for Adiponutrin. Consistent with previously reported data, Desnutrin/ATGL is upregulated by fasting in adipose tissue, whereas Adiponutrin is downregulated. Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL, are strongly induced in the liver of ob/ob mice.Our data support distinct functions for Adiponutrin and Desnutrin/ATGL and raise the possibility that GS2 may contribute significantly to lipolysis in human adipose tissue.

Adolescent pregnancy has been typically linked to a range of adverse outcomes for mother and child. In Australia, Aboriginal and Torres Strait Islander women have a higher proportion of adolescent births compared with other adolescent Australian women, and are at greater risk of poorer psychosocial and clinical outcomes if they are not well supported during pregnancy and beyond. Drawing on existing literature and consultations with young Aboriginal women and health professionals supporting pregnant Aboriginal women in Western Australia, this paper discusses the importance of creating models of antenatal care using a “social determinants of health” framework. Destigmatizing young parenthood and providing continuity of caregiver in culturally safe services, with culturally competent health professionals provides a means to encourage engagement with the health system and improve health outcomes for young mothers and their babies.

Utilizing reverse correlation, we investigated Black and White participants' mental representations of Black-White Biracial people. Across 200 trails, Black and White participants chose which of two faces best fit specific social categories. Using these decisions, we visually estimated Black and White people's mental representations of Biracial people by generating classification images (CIs). Independent raters blind to condition determined that White CI generators' Biracial CI was prototypically Blacker (i.e., more Afrocentric facial features and darker skin tone) than Black CI generators' Biracial CI (Study 1a/b). Furthermore, independent raters could not distinguish between White CI generators' Black and Biracial CIs, a bias not exhibited by Black CI generators (Study 2). A separate task demonstrated that prejudiced White participants allocated fewer imaginary funds to the more prototypically Black Biracial CI (Study 3), providing converging evidence. How phenotypicality bias, the outgroup homogeneity effect, and hypodescent influences people's mental images of ingroup/outgroup members is discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neck musculature is reliably diagnostic of men's formidability and central to several inferences of their physical prowess. These inferences facilitate stereotypes of men's social value from which perceivers estimate their abilities to satisfy reproductive goals related to mate acquisition and parental care. Participants evaluated men's interest in various mating and parenting strategies, wherein men varied in the size of visible neck musculature through trapezii and sternocleidomastoids for perceivers to identify potential reproductive interests and goals. Large trapezii elicited perceptions of men as more effective at protecting offspring, albeit at the expense of nurturance and interest in long-term pair bonds. Results extend previous findings implicating formidability as central to relationship decisions by considering a novel modality., (© 2023 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

The accurate identification of emotion is critical to effectively navigating our social lives. However, it is not clear how distinct types of visual information afford the accurate perception of others' emotion states. Here, we sought to examine the influence of different spatial frequency visual information on emotion categorization, and whether distinctive emotional dimensions (valence and arousal) are differentially influenced by specific spatial frequency content. Across one pilot and two experiments ( N = 603), we tested whether emotional facial expressions that vary in valence, arousal, and functional significance differ in accuracy of categorization as a function of low, intact, and high spatial frequency band information. Overall, we found a general decrease in the breadth of emotional expressions for filtered images but did not see a decrease in accuracy of categorization for the positive emotion, joy. Together, these results suggest that spatial frequency information influences perception of emotional expressions that differ in valence and arousal. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The other-race effect (ORE) is a longstanding phenomenon in experimental psychology, where recognition for same-race faces is superior than for other-race faces. The present research pits two competing theories of perceptual expertise and social motivation against each other to see which is the more robust predictor of the ORE. In Study 1, we measured Black and White participants' prior contact with individuals from the other-race (i.e. expertise) as well as their expected level of future interaction with other-race individuals (i.e. motivation). Of the two theories, anticipated interaction (i.e. motivation) emerged as a significant predictor of the ORE. Study 2 followed the same design, measuring motivation with a self-report assessment of how much participants are willing to have cross-race friendships. Here, neither experience nor motivation predicted the ORE, though an ORE was established. Differences in measures that assess motivation and the experience versus motivation debate are discussed., (© 2022 The British Psychological Society.)

Objective: Recent findings suggest crowd salience heightens pathogen-avoidant motives, serving to reduce individuals' infection risk through interpersonal contact. Such experiences may similarly facilitate the identification, and avoidance, of diseased conspecifics. The current experiment sought to replicate and extend previous crowding research., Methods: In this experiment, we primed participants at two universities with either a crowding or control experience before having them evaluate faces manipulated to appear healthy or diseased by indicating the degree to which they would want to interact with them., Results: Crowding-primed participants reported a more heightened preferences for healthy faces than control-primed participants. Additionally, crowd salience reduced aversion toward healthy faces but did not heighten aversion to diseased faces., Conclusion: Results suggest crowding appears to heighten tolerance for health cues given the heightened proximal threat of infections through interpersonal contact within crowded environments. Conversely, this work extends previous findings by indicating this preference is not rooted in an aversion to cues of poor health. We frame findings from a threat management perspective in understanding how crowding fosters sensitivity toward pathogenic threats., Competing Interests: Conflict of interest On behalf of all authors, the first author reports no conflicts of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.)

Evidence is sparse concerning hypertrophy of cardiomyocytes in left and right ventricles (LV, RV). LV and RV from 105 forensic autopsies were weighed. Cross sectioned cardiac myocyte thicknesses were measured in hematoxylin and eosin-stained paraffin sections. Overweight (OW) is body weight >104.3 kg and hypertension (HT) is mean arterial pressure >106.7 mm Hg assessed from renal histology. Mean RV weights and cardiomyocyte thicknesses held nearly perfect proportionality to the LV values. Exceptions to these patterns were (1) myocytes were slightly thicker than expected in RV of the 27 specimens with the smallest myocyte thicknesses; (2) weights were slightly greater than expected in RV of hypertensives; and (3) myocytes were slightly smaller than expected in RV of OW subjects. Myocyte hypertrophy appears to affect LV and RV equally, preserving constant proportionality between them in a number of conditions which include OW, HT, and perhaps some cardiomyopathies. Ischemic, valvular, and right ventricular disorders determined at autopsy are specifically omitted from this provisional conclusion. The three exceptions from this principle were of small magnitude and unimpressive statistical significance which calls for cautious interpretation. Neither OW nor HT appears to act predictably upon the heart as exclusively volume or pressure overload., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: When overweight or hypertension is present, some patients at first examination exhibit left ventricular (LV) dilation and others concentric hypertrophy that persists indefinitely. Perhaps the ventricles with the fewest myocytes could enter systolic dysfunction with dilation and those with more myocytes may sustain persistent concentric hypertrophy., Methods and Results: Cardiomyocyte numbers, MyN, were counted in paraffin sections of left ventricles from 99 forensic autopsies, excluding instances of coronary heart disease. MyN lacked statistically significant relationships with age, race, sex, height, weight, LV mass, and mean arterial pressure estimated from renal histology. Specimens with the fewest myocytes, however, did manifest significant dilation and thinner chamber walls., Conclusions: The tendency toward an eccentric pattern of hypertrophy in ventricles with the fewest myocytes is a clear conclusion, but has an ambiguous interpretation. This is the pattern expected from the initial hypothesis, but it also has other possible explanations. This ambiguity arises chiefly from limitations in the methods used for estimating MyN. These limitations are accessible to control in future studies. Our findings failed to contradict the hypothesis introduced here. These conclusions are implicit in the underlying observations of MyN constancy across such groupings as sex, height, weight, and LV mass, which provide the less speculative findings., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: External common carotid artery (CCA) diameter and intima-media thickness (IMT) are independently associated with incident stroke and other cardiovascular events. Arterial geometry such as large IMT and large diameter may reflect vulnerable plaques and so impact stroke risk. Finally, arterial changes that exist bilaterally may increase stroke risk., Method: We studied middle-aged men and women (n=7276) from a prospective observational study who had right (R) and left (L) CCA IMT and external diameters measured via B-mode ultrasound (1987-89) in order to categorize CCA geometry. Using side- and gender-specific IMT and diameter medians, we categorized each measurement as large (≥ median) vs. not large (< median) and defined four geometries: both IMT and diameter were large, only one parameter was large, or neither was large (reference group). Participants were followed for first time stroke through December 31, 1999. We used proportional hazards models to assess associations between right and left CCA geometries with new stroke. We also calculated positive and negative likelihood ratios (+LR and -LR) for CCA bilateral phenotypes as a measure of diagnostic accuracy., Results: Presence of both large CCA IMT and large diameter on one side was associated with strong stroke risk even after risk factor adjustment (men: RCCA hazard ratio [HR]=3.7 95% confidence interval [CI]=1.9-7.4; LCCA HR=2.4 95% CI=1.4-4.4; women: RCCA HR=4.0 95% CI=1.5-10.5; LCCA HR=5.7 95% CI=1.7-19.0). Presence of both large IMT and large diameter bilaterally was the strongest predictor of stroke identifying 64% of women and 44% of men who developed strokes. This phenotype showed potential for predicting stroke among individuals (women: +LR=3.1, 95% CI=2.6-3.8; men: +LR=2.3, 95% CI=1.8-2.8)., Conclusion: Bilateral carotid artery geometries may be useful for stroke risk prediction.

Noninvasive measurements of left ventricular wall thickness (LVT) and left ventricular chamber diameter (LVD) allow calculation of expected left ventricular weight (LVW), but not of myocyte breadth (MyB), so that specification of left ventricular hypertrophy (LVH) is not optimal. Hypertrophied hearts, excluding coronary heart disease, and comparison specimens without hypertrophy were compiled into a series of 78 forensic autopsies, wherein LVT, LVD, and LVW were measured. MyB was measured in hematoxylin and eosin-stained paraffin sections. A series of clinical cases tabulating LVD and LVT was assembled from readily available publications. From postmortem data, a regression equation was derived to predict MyB from LVD and LVT. Applying this equation to the clinical data produced a scatter plot closely resembling that in the postmortem dataset. The equation derived here appears to provide valid predictions of cardiomyocyte sizes expected in histological measurements. The finding is the first of its kind and requires further testing for validation or rejection. This is offered as a provisional way to improve the determination of LVH using noninvasive measurements. How this improvement might enhance understanding of the mechanisms for hypertrophy is briefly explored, thus generating working hypotheses., (Copyright © 2012 American Society of Hypertension. All rights reserved.)

Aims: Hypertrophied hearts at autopsy often display excessive coronary artery atherosclerosis, but the histopathology of coronary arteries in hearts with and without cardiomegaly has rarely been compared., Methods: In this study, forensic autopsies provided hearts with unexplained enlargement plus comparison specimens. Right coronary artery was opened longitudinally and flattened for formalin fixation and H&E-stained paraffin sections were cut perpendicular to the endothelial surface. The micro-scopically observed presence or absence of a necrotic atheroma in the specimen was recorded. At multiple sites far removed from any form of atherosclerosis, measurements were taken of intimal thickness, numbers of smooth muscle cells (SMC) and their ratio, the thickness per SMC, averaged over the entire nonatheromatous arterial length. When the mean thickness per SMC exceeded a certain cutoff point, the artery was declared likely to contain a necrotic atheroma., Results: The prevalence of specimens with necrotic atheromas increased stepwise with increasing heart weight, equally with fatal or with incidental cardiomegaly, and equally with hypertension- or obesity-related hypertrophy, rejecting further inclusion of appreciable age, race, or gender effects. The prevalence of specimens with thickness per SMC exceeding the cutoff point was almost always nearly identical to the prevalence of observed necrotic atheroma, showing the two variables to be tightly linked to each other with quantitative consistency across group comparisons of every form., Conclusions: In summary, cardiomegaly, irrespective of the specific cause, seems to accelerate the risk of atheromas, and to do so by first altering the arterial architecture, especially by increasing intimal thickness per SMC.

This chapter reviews a body of evidence concerning the anatomic pathology, pathogenesis, epidemiology and possible etiologic agents of benign essential hypertension in human populations. A core finding serves as the starting point for further reasoning: intimal fibroplasia of renal interlobular arteries (arteriosclerosis) increases with age at varying rates in all populations around the world, and the rise of mean arterial pressure (MAP) with age is closely tied to this process. The weight of evidence favors the view that fibroplasia progresses for wholly unknown reasons, is not accelerated by elevations in MAP, and that it raises MAP in proportion to its severity by creating nephron heterogeneity that initiates Goldblatt mechanisms. This form of hypertension has been designated type 2 to distinguish it from a less common form, called type 1, where the fibroplasia is of mild or minimal degree. This chapter reviews evidence that indicates type 1 does not evolve into type 2 because hypertension is not accelerating the process.Experimental models of hypertension include the Goldblatt model, which resembles some aspects of type 2, and spontaneous genetic models, which mimic some aspects of type 1 hypertension. There is currently no persuasive evidence that type 2 hypertension, as it naturally develops in the human during aging of 50 years or more, can be reproduced in laboratory animals. Clues to the etiology of the arterial fibroplasia that appears to underlie most instances of essential hypertension would best be sought in the study of variations among human populations around the world, and especially of their migrants., (Copyright © 2011 S. Karger AG, Basel.)

Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH). This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height(2.7) as a proxy for lean body mass and body mass index (BMI) as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

Normal, youthful arteries generally maintain constant radius/wall thickness ratios, with the relationship being described by the Laplace Law. Whether this relationship is maintained during aging is unclear. This study first examines the Laplace relationships in postmortem coronary arteries using a novel method to correct measurements for postmortem artifacts, uses data from the literature to provide preliminary validation, and then describes histology associated with low circumferential stress. Measurements of radius and wall thickness, taken at sites free from atheromas, were used with national population estimates of age-, gender-, and race-specific blood pressure data to calculate average circumferential stress within demographic groups. The estimated circumferential stress at ages 55-74 years was about half that at ages 18-24 years because of a disproportionate increase of wall thickness relative to artery radius at older ages, violating the expected relationships described by the Laplace Law. Arteries with low circumferential stress (estimated at sites distant from atherosclerosis) had more necrotic atheromas than arteries with high stress. At sites with low stress and intimal thickening, smooth muscle cells (SMCs) were spread apart, thereby diminishing their density within both the intima and media. Thus, older arteries displayed both low circumferential stress and abundant matrix of low cellularity microscopically. Such changes might alter SMC-matrix interactions.

Objective: To examine the associations of the coronary heart disease (CHD) risk factors with lipid composition of arterial tissue in 397 autopsied subjects 15-34 years of age from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study., Methods and Results: We measured esterified cholesterol, free cholesterol, and phospholipid in the left circumflex coronary artery and two segments of the abdominal aorta, one of which is more susceptible to advanced atherosclerosis than the other, and also measured the major CHD risk factors. Non-HDL cholesterol concentration was positively associated, and HDL cholesterol concentration was negatively associated, with tissue lipids in the left circumflex coronary artery and the abdominal aorta. Hypertension was positively associated with tissue lipids in both arteries. Hyperglycemia was associated with tissue lipids in the left circumflex coronary artery and smoking with lipids in the abdominal aorta. PDAY risk scores summarize the effects of the CHD risk factors on advanced atherosclerosis. These risk scores, computed from the mutable risk factors, were associated with tissue lipids in the left circumflex coronary artery and both segments of the abdominal aorta., Conclusions: The CHD risk factors are associated with lipids in arterial tissue just as they are associated with gross and microscopic lesions. These results support the proposal that early control of risk factors is likely to prevent or delay progression of atherosclerosis and prevent or delay the onset of CHD.