The proportion of loss to follow-up from antiretroviral therapy (ART) and its association with age among adolescents living with HIV in sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV) remains a global health threat, especially in developing countries. The successful scale-up of antiretroviral therapy (ART) programs to address this threat is hindered by a high proportion of patient loss to follow-up (LTFU). LTFU is associated with poor viral suppression and increased mortality. It is particularly acute among adolescents, who face unique adherence challenges. Although LTFU is a critical obstacle on the continuum of care for adolescents, few regional-level studies report the proportion of LTFU among adolescents receiving ART. Therefore, a systematic review and meta-analysis were conducted to estimate the pooled LTFU in ART programs among adolescents living with HIV in sub-Saharan Africa (SSA). METHODS: We searched five databases (PubMed, Embase (Elsevier), PsycINFO, CINAHL, and Scopus) for articles published between 2005 and 2020 and reference lists of included articles. The PRISMA guidelines for systematic reviews were followed. A standardised checklist to extract data was used. Descriptive summaries were presented using narrative tables and figures. Heterogeneity within the included studies was examined using the Cochrane Q test statistics and I2 test. Random effect models were used to estimate the pooled prevalence of LTFU among ALHIV. We used Stata version 16 statistical software for our analysis. RESULTS: Twenty-nine eligible studies (n = 285,564) were included. An estimated 15.07% (95% CI: 11.07, 19.07) of ALHIV were LTFU. Older adolescents (15-19 years old) were 43% (AOR = 0.57, 95% CI: 0.37, 0.87) more likely to be LTFU than younger (10-14 years old) adolescents. We find an insignificant relationship between gender and LTFU (AOR = 0.95, 95% CI: 0.87, 1.03). A subgroup analysis found that regional differences in the proportion of adolescent LTFU were not statistically significant. The trend analysis indicates an increasing proportion of adolescent LTFU over time. CONCLUSIONS AND RECOMMENDATIONS: The proportion of LTFU among HIV-positive adolescents in SSA seems higher than those reported in other regions. Older adolescents in the region are at an increased risk for LTFU than younger adolescents. These findings may help policymakers develop appropriate strategies to retain ALHIV in ART services. Such strategies could include community ART distribution points, appointment spacing, adherence clubs, continuous free access to ART, and community-based adherence support

Sex matters: the frequently overlooked importance of considering sex in computational models

Personalised medicine and the development of a virtual human or a digital twin comprises visions of the future of medicine. To realise these innovations, an understanding of the biology and physiology of all people are required if we wish to apply these technologies at a population level. Sex differences in health and biology is one aspect that has frequently been overlooked, with young white males being seen as the “average” human being. This has not been helped by the lack of inclusion of female cells and animals in biomedical research and preclinical studies or the historic exclusion, and still low in proportion, of women in clinical trials. However, there are many known differences in health between the sexes across all scales of biology which can manifest in differences in susceptibility to diseases, symptoms in a given disease, and outcomes to a given treatment. Neglecting these important differences in the development of any health technologies could lead to adverse outcomes for both males and females. Here we highlight just some of the sex differences in the cardio-respiratory systems with the goal of raising awareness that these differences exist. We discuss modelling studies that have considered sex differences and touch on how and when to create sex-specific models. Scientific studies should ensure sex differences are included right from the study planning phase and results reported using sex as a biological variable. Computational models must have sex-specific versions to ensure a movement towards personalised medicine is realised

Outsiders, insiders, and intermediaries: village health teams' negotiation of roles to provide high quality sexual, reproductive and HIV care in Nakaseke, Uganda.

BACKGROUND: Community health workers, known as Village Health Teams (VHTs) in Uganda, play a central role in increasing access to community-based health services. The objective of this research is to explore tensions that may emerge as VHTs navigate multiple roles as community members and care providers particularly when providing sensitive reproductive health and HIV care. METHODS: Twenty-five VHTs from a rural clinic in Uganda completed semi-structured interviews focused on experiences providing services. Interview questions focused on challenges VHTs face providing services and strategies for improving quality care. After translation from Luganda and transcription, interviews were analyzed using content analysis to identify emergent themes. RESULTS: Most VHTs were female (n = 16). The average age was 46, and average length of VHT work, 11 years. Analyses revealed that all VHTs capitalized upon the duality of their position, shifting roles depending upon context. Three themes emerged around VHTs' perceptions of their roles: community insiders, professional outsiders, and intermediaries. A caregiver "insider" role facilitated rapport and discussion of sensitive issues. As community members, VHTs leveraged existing community structures to educate clients in familiar settings such as "drinking places". However, this role posed challenges as some VHTs felt compelled to share their own resources including food and transport money. Occupying a professional outsider role offered VHTs respect. Their specialized knowledge gave them authority to counsel others on effective forms of family planning. However, some VHTs faced opposition, suspicions about their motives, and violence in this role. In balancing these two roles, the VHTs adopted a third as intermediaries, connecting the community to services in the formalized health care system. Participants suggested that additional training, ongoing supervision, and the opportunity to collaborate with other VHTs would help them better navigate their different roles and, ultimately, improve the quality of service. CONCLUSIONS: As countries scale up family planning and HIV services using VHTs, supportive supervision and ethical dilemma training are recommended so VHTs are prepared for the challenges of assuming multiple roles within communities

Malaria Care-Seeking Behaviour Among HIV-Infected Patients Receiving Antiretroviral Treatment in South-Eastern Nigeria: A Cross-Sectional Study.

This study assesses malaria prevention and treatment behaviour among people living with HIV/AIDS (PLWHA) in Owerri, South Eastern Nigeria. Although Nigeria bears one of the world\u27s largest burdens of both malaria and HIV, there is almost no research studying how co-infected patients manage their care. We systematically sampled 398 PLWHA receiving care at Imo State Specialist Hospital and the Federal Medical Centre in Owerri to complete a structured, pre-tested questionnaire on malaria care-seeking behaviour. Descriptive statistics were reported and chi-square tests and multivariate logistic regressions were also used. The majority of HIV-infected patients (78.9%) reported having had an episode of suspected malaria quarterly or more often. There was a large variation in care-seeking patterns: on suspicion of malaria, 29.1% of participants engaged in self-medication; 39.2% went to drug shops, and only 22.6% visited HIV/AIDS care centres. Almost 40% waited more than 24 hours before initiating treatment. Most (60.3%), reported taking recommended artemisinin-based combination treatments (ACT) but a significant minority took only paracetamol (25.6%) or herbal remedies (3.5%). Most (80%) finished their chosen course of treatment; and completion of treatment was significantly associated with the frequency of suspected malaria occurrence (p = 0.03). Most (62.8%) did not take anti-malaria medication while taking antiretroviral treatment (ART) and almost all (87.6%) reported taking an ACT regimen that could potentially interact with Nigeria\u27s first-line ART regimen. Our findings suggest the need to pay more attention to malaria prevention and control as a crucial element in HIV/AIDS management in this part of Nigeria and other areas where malaria and HIV/AIDS are co-endemic. Also, more research on ART-ACT interactions, better outreach to community-level drug shops and other private sector stakeholders, and clearer guidelines for clinicians and patients on preventing and managing co-infection may be needed. This will require improved collaboration between programmes for both diseases

Effect of a self-care educational intervention to improve self-care adherence among patients with chronic heart failure: a clustered randomized controlled trial in Northwest Ethiopia

Background: As the burden of cardiovascular disease increases in sub-Saharan Africa, there is a growing need for low-cost interventions to mitigate its impact. Providing self-care health education to patients with chronic heart failure (CHF) is recommended as an intervention to prevent complications, improve quality of life, and reduce financial burdens on fragile health systems. However, little is known about health education’s effectiveness at improving CHF self-management adherence in sub-Saharan Africa. Therefore the present study aimed to assess the effectiveness of an educational intervention to improve self-care adherence among patients with CHF at Debre Markos and Felege Hiwot Referral Hospitals in Northwest Ethiopia. Methods: To address this gap, we adapted a health education intervention based on social cognitive theory comprising of intensive four-day training and, one-day follow-up sessions offered every four months. Patients also received illustrated educational leaflets. We then conducted a clustered randomized control trial of the intervention with 186 randomly-selected patients at Debre Markos and Felege Hiwot referral hospitals. We collected self-reported data on self-care behavior before each educational session. We analyzed these data using a generalized estimating equations model to identify health education's effect on a validated 8-item self-care adherence scale. Results: Self-care adherence scores were balanced at baseline. After the intervention, patients in the intervention group (n = 88) had higher adherence scores than those in the control group (n = 98). This difference was statistically significant (β = 4.15, p < 0.05) and increased with each round of education. Other factors significantly associated with adherence scores were being single (β = − 0.25, p < 0.05), taking aspirin (β = 0.76, p < 0.05), and having a history of hospitalization (β = 0.91, p < 0.05). Conclusions: We find that self-care education significantly improved self-care adherence scores among CHF patients. This suggests that policymakers should consider incorporating self-care education into CHF management

Systems Medicine: from molecular features and models to the clinic in COPD

BACKGROUND AND HYPOTHESIS: Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice. OBJECTIVE AND METHOD: Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework. RESULTS: In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice. CONCLUSIONS: The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres