Analysis of Hyperphagia Questionnaire for Clinical Trials (HQ-CT) scores in typically developing individuals and those with Prader-Willi syndrome.

The Hyperphagia Questionnaire for Clinical Trials (HQ-CT) is an observer-reported outcome measure that has been widely used in interventional studies to assess changes in hyperphagic behaviors in individuals with Prader-Willi syndrome (PWS). However, HQ-CT scores in the wider PWS population and the general population have not been reported. Here we report HQ-CT scores from more than 400 individuals with PWS and 600 typical individuals, aged 5-26. Overall, HQ-CT scores were significantly higher in those with PWS compared to typically developing individuals at all ages evaluated. In addition, while HQ-CT scores in the typically developing population decreased with age, scores increased with age in PWS. To further understand the variability of HQ-CT scores in the PWS population, semi-structured interviews were conducted with caregivers of a small subset of adults with PWS who had unexpectedly low HQ-CT scores. These caregivers reported that strict adherence to a food routine, food security measures and supervised food preparation reduced the frequency and intensity of hyperphagic behaviors measured by HQ-CT. Thus, hyperphagic behaviors are captured by the HQ-CT for most individuals with PWS, but for some individuals residing in settings with highly structured food routines, HQ-CT scores may not fully reflect the extent of PWS-associated hyperphagia.

Low acceptance of intimate partner violence by pregnant women in Uganda predicts higher uptake of HIV self-testing among their male partners.

Introduction: Heterosexual couples are at high risk for HIV acquisition in sub-Saharan Africa, and HIV self-testing (HST) is an additional approach to expand access to HIV testing services. However, it is not well known how gender equality is associated with HST.Methods: We used intervention-arm data from a cluster-randomised controlled HST intervention trial (N = 1 618) conducted in Uganda to determine the association between attitudes towards intimate partner violence (IPV), decision-making power and male partner's uptake of HST among heterosexual couples expecting a child in south-central Uganda. The original study question was to assess the impact of providing pregnant women with HST kits to improve male partner's HIV testing rates. For this analysis, the primary exposures were gender equality (measured by male partner's and female partner's attitudes towards IPV and the female partner's household decision-making power), and the primary outcome was the male partner's uptake of HST. Multivariate logistic regression was used for analysis.Results: We found that male partner HST uptake did not vary depending on male partner's attitudes towards IPV or decision-making power; however, male partner HST uptake did depend on the female partner's attitude towards IPV, with 1.76 times more testing (95% CI 1.06-2.92) in couples where the woman had "medium" versus "high" acceptance of IPV, and 1.82 times more testing (95% CI 1.08-3.08) in couples where the woman had "low" versus "high" acceptance of IPV.Conclusions: This study shows the importance of appropriate negative attitudes by women to IPV in increasing male partner's HST uptake to integrate HST into national health care policies.

Incidence of strabismus, strabismus surgeries, and other vision conditions in Prader-Willi syndrome: data from the Global Prader-Willi Syndrome Registry.

BACKGROUND: There is a relative lack of information on the incidence and treatment of vision problems in Prader-Willi syndrome (PWS). Using data from the Global PWS Registry, we performed a cross-sectional study of vision problems in PWS. METHODS: Data, reported by caregivers who completed the Vision Survey in the Global PWS Registry between May of 2015 and March of 2020, were analyzed using descriptive statistics. RESULTS: There were 908 participants in this survey, with a mean age of 14.5 years (range 0-62 years). The prevalence of strabismus in this population was 40 %, with no statistically significant difference in prevalence by genetic subtype. Ninety-one percent of participants with strabismus were diagnosed before 5 years of age. Of those with strabismus, 42 % went on to have strabismus surgery, with 86 % of those having their first strabismus surgery before 5 years of age and 10.1 % having more than one strabismus surgery. Additional vision issues reported included myopia (41 %), hyperopia (25 %), astigmatism (25 %), and amblyopia (16 %). CONCLUSIONS: The prevalence of strabismus, amblyopia, and hyperopia are considerably higher in the PWS population represented in the Global PWS Registry as compared to the general population. People with PWS should be screened early and regularly for vision problems.

Ease of understanding and performing HIV self-tests by pregnant women and their male partners in Uganda: a cross-sectional study.

INTRODUCTION: Understanding and following HIV self-testing (HIVST) instructions is a critical step in the use of HIVST kits. We analyzed data on pregnant women and their partners' self-assessment on the usability of kits delivered by their pregnant women. METHODS: Quantitative data were collected on 399 pregnant women and 238 male partners enrolled in the intervention arm of a large cluster-randomized HIVST trial. Each pregnant woman received HIVST demonstrations, detailed pictorial instructions on how to use OraQuick HIVST kits, and two kits; for herself and her male partner. Follow-up was at one month (baseline for male partners) and 3 months. Descriptive statistics were conducted to compare understanding and following of HIVST instructions by age and education level. RESULTS: The proportion of those who understood HIVST instructions was almost the same (98%) for women and their partners, although partners (26.5%) were nearly twice as likely than women (16.0%) to report needing pretest counseling (Odds ratio [OR] = 1.9, 95% CI: 1.27-2.79). Partners' understanding of the HIVST instructions did not vary by education level, but 4.4% of women with primary education reported difficulty in understanding HIVST instructions compared with 0.5% and 0% of those with secondary and university education, respectively (p = 0.05). However, 5.6% of women aged 30-68 years and 3.3% of partners aged 20-24 years found it more difficult to understand the HIVST instructions. CONCLUSION: Both pregnant women and their male partners were correctly able to perform an HIVST without or (with minimal) support suggesting that this mode of delivery will help the national program reach more men. Because more male partners than women required HIVST pretest counseling support, male-targeted HIVST promotional messages may be needed to increase men's self-efficacy to perform HIVST unsupported.

Variability and change over time of weight and BMI among adolescents and adults with Prader-Willi syndrome: a 6-month text-based observational study.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia. Therefore, we aimed to determine the feasibility of a remote assessment of weight change over time in PWS. METHODS: We developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals. RESULTS: One hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12-48). There was considerable variability in weight across participants (range: 76.8-207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change + 2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects. Participants submitted more than 95% of possible weight data points across the 26 weeks of the study. CONCLUSIONS: This remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.

HIV Oral Self-Testing for Male Partners of Women Attending Antenatal Care in Central Uganda: Uptake of Testing and Linkage to Care in a Randomized Trial.

BACKGROUND: In Uganda, HIV testing rates are approximately 90% among women in antenatal care, with male rates much lower. The World Health Organization has recommended HIV self-testing (HIVST), and one promising model is for women in antenatal care to deliver HIVST kits to their male partners. We investigated the impact of this model on male partner testing rates. SETTING: Three high-volume antenatal clinics in central Uganda. METHODS: We implemented a cluster-randomized controlled trial comparing standard of care to intervention, with the primary outcome of self-reported male partner HIV testing. Women and male partners were followed at 1 and 3 months. We used unadjusted analyses and log-linear models with an intent-to-treat approach accounting for clustering. RESULTS: Study coordinators randomized 1514 women (777 intervention and 737 control). Baseline characteristics were balanced across arms with mean age (SD) of 25.2 (5.5) years and >44% with secondary education or higher. More male partners tested for HIV in intervention [576/746 (77.2%)] versus control [264/709 (37.2%)], P < 0.01. We identified 34 HIV-positive men in intervention versus 10 in control, with 6/26 (23%) and 4/6 (67%), respectively, reporting linking to care. CONCLUSIONS: Our results demonstrate an enormous increase in self-reported partner HIV testing when HIVST is available at home. However, men testing positive through HIVST appeared less likely to link to care than men testing positive at a clinic. These results highlight the potential of HIVST in increasing HIV testing rates, while underscoring the importance of developing effective approaches to maximizing linkage to care among those testing positive through HIVST.

Socio-demographic predictors of gender inequality among heterosexual couples expecting a child in south-central Uganda.

BACKGROUND: Gender inequality is a pervasive problem in sub-Saharan Africa, and has negative effects on health and development. OBJECTIVE: Here, we sought to identify socioeconomic predictors of gender inequality (measured by low decision-making power and high acceptance of intimate partner violence) within heterosexual couples expecting a child in south-central Uganda. METHOD: We used data from a two-arm cluster randomized controlled HIV self-testing intervention trial conducted in three antenatal clinics in south-central Uganda among 1,618 enrolled women and 1,198 male partners. Analysis included Cochran Mantel-Haenzel, proportional odds models, logistic regression, and generalized linear mixed model framework to account for site-level clustering. RESULTS: Overall, we found that 31.1% of men had high acceptance of IPV, and 15.9% of women had low decision-making power. We found religion, education, HIV status, age, and marital status to significantly predict gender equality. Specifically, we observed lower gender equality among Catholics, those with lower education, those who were married, HIV positive women, and older women. CONCLUSION: By better understanding the prevalence and predictors of gender inequality, this knowledge will allow us to better target interventions (increasing education, reducing HIV prevalence in women, targeting interventions different religions and married couples) to decrease inequalities and improve health care delivery to underserved populations in Uganda.

HIV testing preferences among pregnant women attending antenatal care and their male partners: a discrete choice experiment in Uganda.

HIV testing rates remain stubbornly low among men - a crucial target population for reaching the ambitious global and regional goals of the HIV programme. In an era of declining donor funding, identifying cost-effective strategies to increase testing rates amongst men remains paramount. Antenatal care is an effective entry-point for the delivery of HIV testing services for women, and partner testing presents an important opportunity to reach their male partners. We present the results of a discrete choice experiment in Uganda, examining preferences among 824 pregnant women and 896 male partners regarding service delivery characteristics of HIV testing. Both men and women preferred nurse administered testing to self-testing (OR = 0.835; p < 0.001), oral testing over a finger-prick test (OR = 1.176; p < 0.001) and testing with a partner over testing alone (OR = 1.230; p < 0.001). Men had a preference for testing at home compared to testing at a clinic (OR = 1.099; p = 0.024), but women were indifferent regarding the testing location. The cost of testing had the biggest effect on preferences. Free testing was preferred over a cost of US$2.90 (OR = 0.781; p < 0.001) or US$2.00 (OR = 0.670; p < 0.001). Offering an incentive of US$3.40 increased men's preferences compared to a free test (OR = 1.168; p < 0.001), although this did not affect women's preferences. Partner testing linked to antenatal care is a potential strategy to increase testing coverage among men, particularly given the preference for partner testing - provided costs to clients remain low. Future cost-effectiveness evaluations should investigate the economic impact of reaching men using these strategies.

Repeat HIV testing of individuals with discrepant HIV self-test results in Central Uganda.

BACKGROUND: According to the user instructions from the manufacturer of OraQuick HIV self-test (HIVST) kits, individuals whose kits show one red band should be considered to be HIV-negative, no matter how weak the band is. However, recent reports show potential for a second false weak band after storage, thereby creating confusion in the interpretation of results. In this study, we re-tested individuals whose results were initially non-reactive but changed to weak reactive results to determine their true HIV status. METHODS: This study was nested within a large, cluster-randomized HIVST trial implemented among pregnant women attending antenatal care and their male partners in central Uganda between July 2016 and February 2017. Ninety-five initially HIV-negative respondents were enrolled into this study, including 52 whose kits developed a second weak band while in storage and 43 whose kits were interpreted as HIV-positive by interviewers at the next follow-up interview. Respondents were invited to return for repeat HIVST which was performed under the observation of a trained nurse counsellor. After HIVST, respondents underwent blood-based rapid HIV testing as per the national HIV testing algorithm (Determine (Abbot Laboratories), STAT-PAK (Chembio Diagnostic Systems Inc.) and Unigold (Trinity Biotech plc.) and dry blood spots were obtained for DNA/PCR testing. DNA/PCR was considered as the gold-standard HIV testing method. RESULTS: After repeat HIVST, 90 (94.7%) tested HIV-negative; 2 (2.1%) tested HIV-positive; and 3 (3.2%) had missing HIV test results. When respondents were subjected to blood-based rapid HIV testing, 97.9% (93/95) tested HIV-negative while 2.1% (2/95) tested HIV-positive. Finally, when the respondents were subjected to DNA/PCR, 99% (94/95) tested HIV-negative while 1.1% (1/95) tested HIV-positive. CONCLUSIONS: Nearly all initially HIV-negative individuals whose HIVST kits developed a second weak band while in storage or were interpreted as HIV-positive by interviewers were found to be HIV-negative after confirmatory DNA/PCR HIV testing. These findings suggest a need for HIV-negative individuals whose HIVST results change to false positive while under storage or under other sub-optimal conditions to be provided with an option for repeat testing to determine their true HIV status.

Relationship Gender Equality and Couples' Uptake of Oral Human Immunodeficiency Virus Self-Testing Kits Delivered by Pregnant Women in Kenya.

BACKGROUND: Higher gender equality is associated with many human immunodeficiency virus (HIV) preventive behaviors, including HIV testing. HIV self-testing is a relatively new testing technology that could assist with HIV prevention. However, there are no studies examining gender equality and HIV self-testing. We examined the associations between gender equality and couples' uptake of HIV self-testing among heterosexual couples expecting a child in central Kenya. METHODS: This analysis used data from a HIV self-testing randomized intervention trial among pregnant women attending antenatal care and their male partners. The primary exposures were gender equality (measured by the male partner's attitudes toward intimate partner violence, and the woman's report on her household decision making power), and the primary outcome was couples' uptake of HIV self-testing. Generalized linear mixed models framework was used to account for site-level clustering. RESULTS: In comparison to male partners reporting high acceptance of intimate partner violence, couples with male partners reporting medium acceptance (odds ratio, 2.36; 95% confidence interval, 0.99-5.63) or low acceptance (odds ratio, 2.50; 95% confidence interval, 1.20-5.21) were significantly more likely to use HIV self-testing. Gender equality measured by decision making power was not associated with couples' uptake of HIV self-testing. CONCLUSIONS: This study is the first of its kind to examine the association between gender equality and couples' HIV self-testing. This holds important implications for HIV self-testing as we strive to achieve the United Nations Programme on HIV/acquired immune deficiency syndrome goal that 90% of individuals living with HIV should know their status.

HIV Self-Testing Knowledge and Attitudes at Sports-based HIV Prevention Tournaments in Nairobi, Kenya.

HIV remains a major health problem in sub-Saharan Africa, and innovations - such as HIV self-testing (HST) - that break down barriers to testing are required to move toward elimination. Four anonymous cross-sectional surveys were conducted assessing HST knowledge and attitudes among sports-based HIV prevention tournament attendees in Nairobi, Kenya. Results suggest HST may increase testing rates in this population. Participants expressed interest in using HST and were willing to use HST as a tool to motivate others. This poses a unique opportunity for a community intervention aimed to increase knowledge of HST, and to increase HIV testing rates using HST kits.

Social and Demographic Predictors of Gender Inequality Among Heterosexual Couples Expecting a Child in Central Kenya.

Imbalance of power and equality in sexual relationships is linked to health in various ways, including (1) reduced ability to get information or take action, (2) increased violence between partners, and (3) influence on the reduced use of health services. While there has been research assessing multiple social and economic variables related to gender inequality, studies have used many different definitions of gender inequality, and there is a lack of this research within a pregnancy context. Here, we attempt to identify social and economic predictors of gender inequality (measured by decision-making power and acceptance of intimate partner violence) within heterosexual couples expecting a child in central Kenya. We ran a secondary data analysis using data from a three-arm individually randomized controlled HIV self-testing intervention trial conducted in 14 antenatal clinics in central and eastern Kenya among 1410 women and their male partners. The analysis included Cochran Mantel-Haenszel, logistic regression, proportional odds models, and generalized linear mixed model (GLMM) framework to account for site-level clustering. Overall, we show that there are significant social and economic variables associated with acceptance of intimate partner violence including higher age, being married, "other" religion, lower partner education, higher wealth status, and variables associated with decision-making power including lower partner education and lack of equality in earnings. This study contributes to the literature on the influence of social and economic factors on gender inequality, especially in Kenya which has a high burden of HIV/AIDS. Our results show some areas to improve these specific factors (including education and employment opportunities) or create interventions for targeted populations to potentially improve gender equality in heterosexual pregnant couples in Kenya.

Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774).

Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors of prolyl oligopeptidase (POP).

We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket.