Measures and Impact of Caseload Surge During the COVID-19 Pandemic: A Systematic Review.

OBJECTIVES: COVID-19 pandemic surges strained hospitals globally. We performed a systematic review to examine measures of pandemic caseload surge and its impact on mortality of hospitalized patients. DATA SOURCES: PubMed, Embase, and Web of Science. STUDY SELECTION: English-language studies published between December 1, 2019, and November 22, 2023, which reported the association between pandemic "surge"-related measures and mortality in hospitalized patients. DATA EXTRACTION: Three authors independently screened studies, extracted data, and assessed individual study risk of bias. We assessed measures of surge qualitatively across included studies. Given multidomain heterogeneity, we semiquantitatively aggregated surge-mortality associations. DATA SYNTHESIS: Of 17,831 citations, we included 39 studies, 17 of which specifically described surge effects in ICU settings. The majority of studies were from high-income countries ( n = 35 studies) and included patients with COVID-19 ( n = 31). There were 37 different surge metrics which were mapped into four broad themes, incorporating caseloads either directly as unadjusted counts ( n = 11), nested in occupancy ( n = 14), including additional factors (e.g., resource needs, speed of occupancy; n = 10), or using indirect proxies (e.g., altered staffing ratios, alternative care settings; n = 4). Notwithstanding metric heterogeneity, 32 of 39 studies (82%) reported detrimental adjusted odds/hazard ratio for caseload surge-mortality outcomes, reporting point estimates of up to four-fold increased risk of mortality. This signal persisted among study subgroups categorized by publication year, patient types, clinical settings, and country income status. CONCLUSIONS: Pandemic caseload surge was associated with lower survival across most studies regardless of jurisdiction, timing, and population. Markedly variable surge strain measures precluded meta-analysis and findings have uncertain generalizability to lower-middle-income countries (LMICs). These findings underscore the need for establishing a consensus surge metric that is sensitive to capturing harms in everyday fluctuations and future pandemics and is scalable to LMICs.

The effect of alcohol, tobacco, and other drug use on vaccine acceptance, uptake, and adherence: a systematic review.

BACKGROUND: Vaccine hesitancy is increasingly recognized as a health challenge affecting populations worldwide. Given the biological vulnerabilities and structural barriers people who use substances and/or have behavioral addictions face, this systematic review aims to evaluate whether this subpopulation is less prone to adhere to vaccination recommendations. METHODS: Electronic searches of published original research were conducted in PubMed, EMBASE, Scopus, and PsycINFO from database inception to December 2022. Our strategy encompassed retrievals regardless of languages and date of publication. Animal studies, abstracts without a full manuscript, and studies which were considered to have lower robustness of scientific evidence were excluded. Outcomes measured were vaccine acceptance, uptake, and adherence. Results were interpreted through a narrative synthesis. RESULTS: The search yielded 103 retrievals encompassing data collected on 5 576 374 persons who were predominantly residents of Europe (n = 39) and North America (n = 27). Tobacco use, the substance for which many studies were found (n = 91), was significantly associated with poorer vaccine acceptance, uptake and adherence for influenza, COVID-19, human papillomavirus (HPV), and maternal and childhood vaccines. Peri-natal and parental substance use was identified as a risk factor for suboptimal vaccine-related outcomes concerning maternal COVID-19 and childhood vaccines. Finally, people identified as 'using', 'abusing', or 'misusing' drugs or substances may be at decreased odds of all outcomes in various vaccines. CONCLUSIONS: Collectively, the studies identified several groups with statistically significant greater vaccine hesitancy and decreased engagement among whom targeted measures could be beneficial. Timely evidence, especially on behavioral addictions and substances besides tobacco, is lacking, and warrants urgent attention.

Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID-19: Results of a systematic review and meta-analysis.

BACKGROUND: Determining how prior immune checkpoint inhibitor (ICI) therapy influences outcomes in cancer patients presenting with COVID-19 is essential for patient management but must account for confounding variables. METHODS: We performed a systematic review and meta-analysis of studies reporting adjusted effects of ICIs on survival, severe events, or hospitalisation in cancer patients with COVID-19 based on variables including age, gender, diabetes mellitus, hypertension (HTN), chronic obstructive pulmonary disease, and other comorbidities. When adjusted effects were unavailable, unadjusted data were analysed. RESULTS: Of 42 observational studies (38 retrospective), 7 reported adjusted outcomes for ICIs and 2 provided sufficient individual patient data to calculate adjusted outcomes. In eight studies, adjusted outcomes were based on ≤7 variables. Over all studies, only one included >100 ICI patients while 26 included <10. ICIs did not alter the odds ratio (95%CI) (OR) of death significantly (random effects model), across adjusted (n = 8) [1.31 (0.58-2.95) p = 0.46; I2  = 42%, p = 0.10], unadjusted (n = 30) [1.06 (0.85-1.32) p = 0.58; I2  = 0%, p = 0.76] or combined [1.09 (0.88;1.36) p = 0.41; I2  = 0%, p = 0.5)] studies. Similarly, ICIs did not alter severe events significantly across adjusted (n = 5) [1.20 (0.30-4.74) p = 0.73; I2  = 52%, p = 0.08], unadjusted (n = 19) [(1.23 (0.87-1.75) p = 0.23; I2  = 16%, p = 0.26] or combined [1.26 (0.90-1.77) p = 0.16; I2  = 25%, p = 0.14] studies. Two studies provided adjusted hospitalisation data and when combined with 13 unadjusted studies, ICIs did not alter hospitalisation significantly [1.19 (0.85-1.68) p = 029; I2  = 5%, p = 0.40]. Results of sensitivity analyses examining ICI effects based on 5 variables were inconclusive. Certainty of evidence was very low. CONCLUSIONS: Across studies with adjusted and unadjusted results, ICIs did not alter outcomes significantly. But studies with comprehensive adjusted outcome data controlling for confounding variables are necessary to determine whether ICIs impact COVID-19 outcomes in cancer patients.

Effects of chloroquine or hydroxychloroquine treatment on non-SARS-CoV2 viral infections: A systematic review of clinical studies.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.

A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings.

PURPOSE: Secondary findings (SFs) are present in 1-4% of individuals undergoing genome/exome sequencing. A review of how SFs are disclosed and what outcomes result from their receipt is urgent and timely. METHODS: We conducted a systematic literature review of SF disclosure practices and outcomes after receipt including cascade testing, family and provider communication, and health-care actions. Of the 1,184 nonduplicate records screened we summarize findings from 27 included research articles describing SF disclosure practices, outcomes after receipt, or both. RESULTS: The included articles reported 709 unique SF index recipients/families. Referrals and/or recommendations were provided 647 SF recipients and outcome data were available for 236. At least one recommended evaluation was reported for 146 SF recipients; 16 reports of treatment or prophylactic surgery were identified. We found substantial variations in how the constructs of interest were defined and described. CONCLUSION: Variation in how SF disclosure and outcomes were described limited our ability to compare findings. We conclude the literature provided limited insight into how the American College of Medical Genetics and Genomics (ACMG) guidelines have been translated into precision health outcomes for SF recipients. Robust studies of SF recipients are needed and should be prioritized for future research.

Effects of Cognitive Reserve on Cognition in Individuals With Central Nervous System Disease.

Cognitive reserve (CR) has been proposed to account for functional outcome differences in brain pathology and its clinical manifestations. The purpose of our paper is to systematically review the effects of CR on cognitive outcomes in individuals with neurodegenerative and structural CNS diseases. We performed a systematic search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsychInfo using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Seventeen studies met the predetermined inclusion criteria and were selected for review. Education level was the most commonly used measure for CR, and various neuropsychological tests were used to measure cognitive outcomes. Regardless of the CNS disease of the individuals, almost all of the studies reported a positive association between CR and cognitive outcomes when they were evaluated cross-sectionally. However, when evaluated longitudinally, CR had either no effect on, or a negative association with, cognitive outcomes. Based on studies across a broad spectrum of CNS diseases, our findings suggest that CR may serve as a predictor of cognitive outcomes in individuals with CNS diseases. However, studies to date are limited by a lack of imaging analyses and standardized assessment strategies. The ability to use a standardized measure to assess the longitudinal effects of CR may allow for the development of more targeted treatment methods, resulting in improved disease outcomes for individuals.

Low prevalence of viable Toxoplasma gondii in fresh, unfrozen American pasture-raised pork and lamb from retail meat stores in the United States.

In a national survey of fresh, unfrozen, American pasture-raised lamb and pork, the prevalence of viable Toxoplasma gondii was determined in 1500 samples selected by random multistage sampling (750 pork, 750 lamb) obtained from 250 retail meat stores from 10 major geographic areas in the USA. Each sample consisted of a minimum of 500g of meat purchased from the retail meat case. To detect viable T. gondii, 50g meat samples of each of 1500 samples were bioassayed in mice. Viable T. gondii was isolated from 2 of 750 lamb samples (unweighted: 0.19%, 0.00-0.46%; weighted: 0.04%, 0.00-0.11%) and 1 of 750 pork samples (unweighted: 0.12%, 0.00-0.37%; weighted: 0.18%, 0.00-0.53%) samples. Overall, the prevalence of viable T. gondii in these retail meats was very low. Nevertheless, consumers, especially pregnant women, should be aware that they can acquire T. gondii infection from ingestion of undercooked meat. Cooking meat to an internal temperature of 66°C kills T. gondii.

Perspectives on contraceptive implant use in women living with HIV in Cape Town, South Africa: a qualitative study among primary healthcare providers and stakeholders.

BACKGROUND: This study explored primary healthcare provider and HIV/contraception expert stakeholder perspectives on South Africa's public sector provision of contraceptive implants to women living with HIV. We investigated the contraceptive service-impact of official advice against provision of implants to women using the HIV antiretroviral drug, efavirenz, issued by the South African National Department of Health (NDoH) in 2014. METHODS: Qualitative data was collected in Cape Town in 2017 from primary healthcare contraceptive providers in four clinics that provide implants, as well as from other expert stakeholders selected for expertise in HIV and/or contraception. In-depth interviews and a group discussion explored South Africa's implant introduction and implant provision to women living with HIV. Data was analysed using an inductive thematic analysis approach. RESULTS: Interviews were conducted with 10 providers and 10 stakeholders. None of the four clinics where the providers worked currently offered the implant to women living with HIV. Stakeholders confirmed that this was consistent with patterns of implant provision at primary healthcare facilities across Cape Town. Factors contributing to providers' decisions to suspend provision of the implant to women living with HIV included: inadequate initial and ongoing provider training; interpretation of NDoH communications about implant use with efavirenz; provider unwillingness to risk harming clients and concerns about professional liability; and other pressures related to provider capacity. CONCLUSIONS: All South African women, including those living with HIV, should have access to the full range of contraceptive options for which they are medically eligible. Changing guidance should be initiated and communicated in consultation with primary-level providers and service beneficiaries. Guidance issued to providers needs to be clear and fully evidence-informed, and its correct interpretation and implementation facilitated and monitored. Guidance should be accompanied by provider training, as well as counselling messages and tools to support providers. Generalized retraining of providers in rights-based, client-centred family planning, and in particular implant provision for women with HIV, is needed. These recommendations accord with the right of women living with HIV to access the highest possible standard of sexual and reproductive healthcare, including informed contraceptive choice and access to the contraceptive implant.

Levels of resilience and delivery of HIV care in response to urban violence and crime.

AIMS: To understand the impact of urban violence and crime on HIV care delivery. BACKGROUND: Urban violence and crime can put pressure on the healthcare system and on nursing staff. Whilst there is research about the impact this has at the individual level, there is less research that places this in the context of the overall social eco-system. DESIGN: A qualitative design using inductive thematic analysis. METHODS: Between July 2016 - February 2017, we conducted in-depth interviews with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa. RESULTS: The effects of crime and violence were evident at multiple levels resulting in participants feeling "safe and unsafe" in a context where people view crime as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community, and organizational levels and enabled continued delivery of HIV care. CONCLUSION: The findings demonstrate the potential role of resilience in the social eco-health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism. IMPACT: This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco-system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime.

The Empower Nudge lottery to increase dual protection use: a proof-of-concept randomised pilot trial in South Africa.

The objective of this study is to measure the preliminary efficacy of a pilot intervention, grounded in behavioural economics, increasing adherence of dual protection (simultaneous use of effective modern contraception and a barrier method, such as a condom) to protect against HIV, other sexually transmitted infections, and unintended pregnancy. Between 2015 and 2016, 100 women aged 18-40 years, seeking post-abortion care in Cape Town, South Africa were recruited to Empower Nudge, a randomised controlled trial to test a lottery incentive intervention designed to increase dual protection. At baseline, the mean age of participants was 27 years; 82% of them were from South Africa; 58% self-identified as Black African; average education completed was 11.7 years. At three months, assignment to the lottery intervention was associated with higher odds of returning for study visits (OR: 6.0; 95%CI: 2.45 to 14.7, p < 0.01), higher condom use (OR: 4.5; 95%CI: 1.43 to 14.1; p < 0.05), and higher use of dual protection (OR: 3.16; 95%CI: 1.01 to 9.9; p < 0.05). Only 60% of the study population returned after three months and only 38% returned after six months. Women who receive post-abortion care represent a neglected population with an urgent need for HIV and pregnancy prevention. Dual protection is a critically important strategy for this population. Lottery-based behavioural economics strategies may offer possible ways to increase dual protection use in this population. Further research with larger samples, longer exposure time, and more sites is needed to establish fully powered efficacy of lottery incentives for dual protection; using objective verification for monitoring.

Opportunities for linking research to policy: lessons learned from implementation research in sexual and reproductive health within the ANSER network.

BACKGROUND: The uptake of findings from sexual and reproductive health and rights research into policy-making remains a complex and non-linear process. Different models of research utilisation and guidelines to maximise this in policy-making exist, however, challenges still remain for researchers to improve uptake of their research findings and for policy-makers to use research evidence in their work. METHODS: A participatory workshop with researchers was organised in November 2017 by the Academic Network for Sexual and Reproductive Health and Rights Policy (ANSER) to address this gap. ANSER is a consortium of experienced researchers, some of whom have policy-making experience, working on sexual and reproductive health and rights issues across 16 countries and 5 continents. The experiential learning cycle was used to guide the workshop discussions based on case studies and to encourage participants to focus on key lessons learned. Workshop findings were thematically analysed using specific stages from Hanney et al.'s (Health Res Policy Syst 1:2, 2003) framework on the place of policy-making in the stages of assessment of research utilisation and outcomes. RESULTS: The workshop identified key strategies for translating research into policy, including joint agenda-setting between researchers and policy-makers, as well as building trust and partnerships with different stakeholders. These were linked to stages within Hanney et al.'s framework as opportunities for engaging with policy-makers to ensure uptake of research findings. CONCLUSION: The engagement of stakeholders during the research development and implementation phases, especially at strategic moments, has a positive impact on uptake of research findings. The strategies and stages described in this paper can be applied to improve utilisation of research findings into policy development and implementation globally.

An Approach to Developing a Prediction Model of Fertility Intent Among HIV-Positive Women and Men in Cape Town, South Africa: A Case Study.

As a 'case-study' to demonstrate an approach to establishing a fertility-intent prediction model, we used data collected from recently diagnosed HIV-positive women (N = 69) and men (N = 55) who reported inconsistent condom use and were enrolled in a sexual and reproductive health intervention in public sector HIV care clinics in Cape Town, South Africa. Three theoretically-driven prediction models showed reasonable sensitivity (0.70-1.00), specificity (0.66-0.94), and area under the receiver operating characteristic curve (0.79-0.89) for predicting fertility intent at the 6-month visit. A k-fold cross-validation approach was employed to reduce bias due to over-fitting of data in estimating sensitivity, specificity, and area under the curve. We discuss how the methods presented might be used in future studies to develop a clinical screening tool to identify HIV-positive individuals likely to have future fertility intent and who could therefore benefit from sexual and reproductive health counseling around fertility options.

Coming of age? Women's sexual and reproductive health after twenty-one years of democracy in South Africa.

This paper is a sequel to a 2004 article that reviewed South Africa's introduction of new sexual and reproductive health (SRH) and rights laws, policies and programmes, a decade into democracy. Similarly to the previous article, this paper focuses on key areas of women's SRH: contraception and fertility, abortion, maternal health, HIV, cervical and breast cancer and sexual violence. In the last decade, South Africa has retained and expanded its sexual and reproductive health and rights (SRHR) policies in the areas of abortion, contraception, youth and HIV treatment (with the largest antiretroviral treatment programme in the world). These are positive examples within the SRHR policy arena. These improvements include fewer unsafe abortions, AIDS deaths and vertical HIV transmission, as well as the public provision of a human papillomavirus vaccine to prevent cervical cancer. However, persistent socio-economic inequities and gender inequality continue to profoundly affect South African women's SRHR. The state shows mixed success over the past two decades in advancing measurable SRH social justice outcomes, and in confronting and ameliorating social norms that undermine SRHR.

Pregnant women's experiences of male partner involvement in the context of prevention of mother-to-child transmission in Khayelitsha, South Africa.

Male partner involvement (MPI) has been identified as a priority intervention in programmes for the prevention of mother-to-child transmission (PMTCT) of HIV, but rates of MPI remain low worldwide. This study used a quantitative survey (n=170) and two focus group discussions (FGDs) with 16 HIV-positive pregnant women attending a public sector antenatal care service in Khayelitsha, South Africa, to examine the determinants of high levels of involvement and generate a broader understanding of women's experiences of MPI during pregnancy. Among survey participants, 74% had disclosed their status to their partner, and most reported high levels of communication around HIV testing and preventing partner transmission, as well as high levels of MPI. High MPI was significantly more likely among women who were cohabiting with their partner; who had reportedly disclosed their HIV status to their partner; and who reported higher levels of HIV-related communication with their partner. FGD participants discussed a range of ways in which partners can be supportive during pregnancy, not limited to male attendance of antenatal care. MPI appears to be a feasible intervention in this context, and MPI interventions should aim to encourage male partner attendance of antenatal care as well as greater involvement in pregnancy more generally. Interventions that target communication are needed to facilitate HIV-related communication and disclosure within couples. MPI should remain a priority intervention in PMTCT programmes, and increased efforts should be made to promote MPI in PMTCT.

The HIV epidemic and sexual and reproductive health policy integration: views of South African policymakers.

BACKGROUND: Integration of sexual and reproductive health (SRH) and HIV policies and services delivered by the same provider is prioritised worldwide, especially in sub-Saharan Africa where HIV prevalence is highest. South Africa has the largest antiretroviral treatment (ART) programme in the world, with an estimated 2.7 million people on ART, elevating South Africa's prominence as a global leader in HIV treatment. In 2011, the Southern African HIV Clinicians Society published safer conception guidelines for people living with HIV (PLWH) and in 2013, the South African government published contraceptive guidelines highlighting the importance of SRH and fertility planning services for people living with HIV. Addressing unintended pregnancies, safer conception and maternal health issues is crucial for improving PLWH's SRH and combatting the global HIV epidemic. This paper explores South African policymakers' perspectives on public sector SRH-HIV policy integration, with a special focus on the need for national and regional policies on safer conception for PLWH and contraceptive guidelines implementation. METHODS: It draws on 42 in-depth interviews with national, provincial and civil society policymakers conducted between 2008-2009 and 2011-2012, as the number of people on ART escalated. Interviews focused on three key domains: opinions on PLWH's childbearing; the status of SRH-HIV integration policies and services; and thoughts and suggestions on SRH-HIV integration within the restructuring of South African primary care services. Data were coded and analysed according to themes. RESULTS: Participants supported SRH-HIV integrated policy and services. However, integration challenges identified included a lack of policy and guidelines, inadequately trained providers, vertical programming, provider work overload, and a weak health system. Participants acknowledged that SRH-HIV integration policies, particularly for safer conception, contraception and cervical cancer, had been neglected. Policymakers supported public sector adoption of safer conception policy and services. Participants interviewed after expanded ART were more positive about safer conception policies for PLWH than participants interviewed earlier. CONCLUSION: The past decade's HIV policy changes have increased opportunities for SRH-HIV integration. The findings provide important insights for international, regional and national SRH-HIV policy and service integration initiatives.

Health care provider perspectives on pregnancy and parenting in HIV-positive individuals in South Africa.

BACKGROUND: Within the health system, limited attention is given to supporting the fertility and parenting desires on HIV-positive people. In this study, we explore health care providers' knowledge and perspectives on safer conception and alternate parenting strategies for HIV-positive people. METHODS: Between November 2007 and January 2008, in-depth interviews were conducted with 28 health care workers involved in providing HIV and/or antiretroviral services at public sector clinics in Cape Town, South Africa. Views on sexual and reproductive health services, pregnancy, childbearing and parenting in HIV-positive men and women were explored using a semi-structured interview guide. Data were analyzed using a thematic approach. RESULTS: Providers recognized the sexual and reproductive rights of HIV-positive individuals, but struggled with the tension between supporting these rights and concerns about spreading infection. Limited knowledge of safer conception methods constrained their ability to counsel and support clients in realizing fertility desires. Providers believed that parenting alternatives that do not maintain biological and cultural linkage are unlikely to be acceptable options. CONCLUSIONS: Health care provider training and support is critical to providing comprehensive sexual and reproductive health care and meeting the fertility desires of HIV-positive people.

Conscientious objection and its impact on abortion service provision in South Africa: a qualitative study.

BACKGROUND: Despite abortion being legally available in South Africa after a change in legislation in 1996, barriers to accessing safe abortion services continue to exist. These barriers include provider opposition to abortion often on the grounds of religious or moral beliefs including the unregulated practice of conscientious objection. Few studies have explored how providers in South Africa make sense of, or understand, conscientious objection in terms of refusing to provide abortion care services and the consequent impact on abortion access. METHODS: A qualitative approach was used which included 48 in-depth interviews with a purposively selected population of abortion related health service providers, managers and policy influentials in the Western Cape Province, South Africa. Data were analyzed using a thematic analysis approach. RESULTS: The ways in which conscientious objection was interpreted and practiced, and its impact on abortion service provision was explored. In most public sector facilities there was a general lack of understanding concerning the circumstances in which health care providers were entitled to invoke their right to refuse to provide, or assist in abortion services. Providers seemed to have poor understandings of how conscientious objection was to be implemented, but were also constrained in that there were few guidelines or systems in place to guide them in the process. CONCLUSIONS: Exploring the ways in which conscientious objection was interpreted and applied by differing levels of health care workers in relation to abortion provision raised multiple and contradictory issues. From providers' accounts it was often difficult to distinguish what constituted confusion with regards to the specifics of how conscientious objection was to be implemented in terms of the Choice on Termination of Pregnancy Act, and what was refusal of abortion care based on opposition to abortion in general. In order to disentangle what is resistance to abortion provision in general, and what is conscientious objection on religious or moral grounds, clear guidelines need to be provided including what measures need to be undertaken in order to lodge one's right to conscientious objection. This would facilitate long term contingency plans for overall abortion service provision.

Experiences and conceptualizations of sexual debut from the narratives of South African men and women in the context of HIV/AIDS.

Given the pivotal role of first sex in the development of sexual and reproductive health (SRH) practices, there is a need for more contextualised and nuanced understandings of young people's early sexual debut experiences. This study used sexual history narratives to investigate how South African men and women experience and attribute meaning to their sexual debut, and their SRH practices. In light of the gendered disparities among young people's SRH awareness and risk, differences between men and women's narratives of sexual debut were assessed. Fifty sexual history interviews were conducted with men and 25 sexual history interviews with women, with participants purposively sampled from three age categories, a range of cultural and racial backgrounds and urban and rural sites across five provinces. Narrative interviews were designed to elicit stories around participants' early knowledge of sex and sexual experimentation, their range of sexual relationships and SRH practices. The data were analysed using a thematic approach. Participants generally reflected on their early sexual experiences with feelings of inadequacy and disappointment. While men appeared to hold greater decision-making power than women at sexual debut, descriptions of men's early sexual experiences were often characterised by respect, intimacy and vulnerability. Many men attributed the timing of their sexual debut to peer pressure, which typically generated higher social status and rarely included consideration of the need to practice safer sex. Several women felt pressured by their partner to sexually debut, which could have informed their perceptions of men being sexually controlling and aggressive. The study demonstrates the value of a narrative approach for generating insights on young people's sexual debut experiences and SRH practices, and the underlying gendered norms and expectations that shape these. The findings indicate the need for gender transformative HIV interventions to take into the diversity of young people's SRH needs and social realities.

The effect of 60 days of 6° head-down-tilt bed rest on circulating adropin, irisin, retinol binding protein-4 (RBP4) and individual metabolic responses in young, healthy males.

Background: Alterations in the circulating concentrations and target-tissue action of organokines underpin the development of insulin resistance in microgravity and gravity deprivation. The purpose of this study was to examine changes in circulating adropin, irisin, retinol binding protein-4 (RBP4), and the metabolic response of healthy young males following 60 days of 6° head-down-tilt (HDT) bed rest, with and without reactive jump training (RJT), to explore links with whole-body and tissue-specific insulin sensitivity. To our knowledge, this is the first time that adropin, irisin, and RBP4 have been studied in HDT bed rest. Methods: A total of 23 male subjects (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were exposed to 60 days of 6° HDT bed rest and randomized to a control (CTRL, n = 11) or a RJT (JUMP, n = 12) group (48 sessions with ≤4 min total training time per session). Circulating adropin, irisin, and RBP4 were quantified in fasting serum before and after HDT bed rest. A subanalysis was performed a posteriori to investigate individual metabolic responses post-HDT bed rest based on subjects that showed an increase or decrease in whole-body insulin sensitivity (Matsuda index). Results: There were significant main effects of time, but not group, for decreases in adropin, irisin, Matsuda index, and liver insulin sensitivity following HDT bed rest (p < 0.05), whereas RBP4 did not change. The subanalysis identified that in a subgroup with decreased whole-body insulin sensitivity (n = 17), RBP4 increased significantly, whereas adropin, irisin, and liver insulin sensitivity were all decreased significantly following HDT bed rest. Conversely, in a subgroup with increased whole-body insulin sensitivity (n = 6), liver insulin sensitivity increased significantly after HDT bed rest, whereas adropin, irisin, and RBP4 did not change. Conclusion: Investigating individual metabolic responses has provided insights into changes in circulating adropin, irisin, RBP4, in relation to insulin sensitivity following HDT bed rest. We conclude that adropin, irisin, and RBP4 are candidate biomarkers for providing insights into whole-body and tissue-specific insulin sensitivity to track changes in physiological responsiveness to a gravity deprivation intervention in a lean male cohort.

The crosstalk between fibroblast growth factor 21 (FGF21) system and substance use.

Existing literature indicates that communication between the central nervous system and the peripheral nervous system is disrupted by substance use disorders (SUDs), including alcohol use disorder (AUD). Fibroblast growth factor 21 (FGF21), a liver-brain axis hormone governing energy homeostasis, has been shown to modulate alcohol intake/preference and other substances. To further elucidate the relationship between FGF21, alcohol use, and other substance use, we conducted a scoping review to explore the association between FGF21 and SUDs. Increases in FGF21 reduce alcohol consumption while suppressing FGF21 increases alcohol consumption, demonstrating an inverse relationship. Alcohol elevates FGF21 levels primarily via the liver, subsequently promoting neuronal signals to curb alcohol intake. FGF21 activation engages molecular pathways that defend against alcohol-induced fat accumulation, oxidative stress, and inflammation. Considering the bidirectional association between FGF21 and alcohol, further studies on the FGF21 system as a potential pharmacotherapy for AUD and alcohol-associated liver disease are warranted.