Bayesian spatial modelling of intimate partner violence and associated factors among adult women and men: evidence from 2019/2020 Rwanda Demographic and Health Survey.

BACKGROUND: Intimate partner violence (IPV) remains a global public health concern for both men and women. Spatial mapping and clustering analysis can reveal subtle patterns in IPV occurrences but are yet to be explored in Rwanda, especially at a lower small-area scale. This study seeks to examine the spatial distribution, patterns, and associated factors of IPV among men and women in Rwanda. METHODS: This was a secondary data analysis of the 2019/2020 Rwanda Demographic and Health Survey (RDHS) individual-level data set for 1947 women aged 15-49 years and 1371 men aged 15-59 years. A spatially structured additive logistic regression model was used to assess risk factors for IPV while adjusting for spatial effects. The district-level spatial model was adjusted for fixed covariate effects and was implemented using a fully Bayesian inference within the generalized additive mixed effects framework. RESULTS: IPV prevalence amongst women was 45.9% (95% Confidence interval (CI): 43.4-48.5%) while that for men was 18.4% (95% CI: 16.2-20.9%). Using a bivariate choropleth, IPV perpetrated against women was higher in the North-Western districts of Rwanda whereas for men it was shown to be more prevalent in the Southern districts. A few districts presented high IPV for both men and women. The spatial structured additive logistic model revealed higher odds for IPV against women mainly in the North-western districts and the spatial effects were dominated by spatially structured effects contributing 64%. Higher odds of IPV were observed for men in the Southern districts of Rwanda and spatial effects were dominated by district heterogeneity accounting for 62%. There were no statistically significant district clusters for IPV in both men or women. Women with partners who consume alcohol, and with controlling partners were at significantly higher odds of IPV while those in rich households and making financial decisions together with partners were at lower odds of experiencing IPV. CONCLUSION: Campaigns against IPV should be strengthened, especially in the North-Western and Southern parts of Rwanda. In addition, the promotion of girl-child education and empowerment of women can potentially reduce IPV against women and girls. Furthermore, couples should be trained on making financial decisions together. In conclusion, the implementation of policies and interventions that discourage alcohol consumption and control behaviour, especially among men, should be rolled out.

Using joint models to study the association between CD4 count and the risk of death in TB/HIV data.

BACKGROUND: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model. METHODS: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data. RESULTS: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84). CONCLUSIONS: In this paper we have shown that the "current value" association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes.

Prevalence and factors associated with self-reported HIV testing among adolescent girls and young women in Rwanda: evidence from 2019/20 Rwanda Demographic and Health Survey.

BACKGROUND: HIV/AIDS remains a major public health problem globally. The majority of people living with HIV are from Sub-Saharan Africa, particularly adolescent girls and young women (AGYW) aged 15-24 years. HIV testing is crucial as it is the gateway to HIV prevention, treatment, and care; therefore this study determined the prevalence and factors associated with self-reported HIV testing among AGYW in Rwanda. METHODS: We conducted secondary data analysis on the AGYW using data extracted from the nationally representative population-based 2019/2020 cross-sectional Rwanda Demographic and Health Survey (DHS). We described the characteristics of study participants and determined the prevalence of HIV testing and associated factors using the multivariable logistic regression model. We adjusted all our analyses for unequal sampling probabilities using survey weights. RESULTS: There were a total of 5,732 AGYW, with the majority (57%) aged 15-19 years, 83% were not living with a man, 80% were from rural areas, 29% were from the East region, and 20% had a history of pregnancy. Self-reported HIV testing prevalence was 55.4% (95%CI: 53.7 to 57.0%). The odds of ever having an HIV test were significantly higher for those aged 20-24 years (aOR 2.87, 95%CI: 2.44 to 3.37); with higher education (aOR 2.41, 95%CI:1.48 to 3.93); who were rich (aOR 2.06, 95%CI:1.57 to 2.70); with access to at least one media (aOR 1.64, 95%CI: 1.14 to 2.37); who had ever been pregnant (aOR 16.12, 95%CI: 9.60 to 27.07); who ever had sex (aOR 2.40, 95%CI: 1.96 to 2.95); and those who had comprehensive HIV knowledge (aOR 1.34, 95%CI: 1.17 to 1.54). CONCLUSIONS: We report an unmet need for HIV testing among AGYW in Rwanda. We recommend a combination of strategies to optimize access to HIV testing services, especially among the 15-19 years adolescent girls, including facility-based testing, school and community outreach, awareness campaigns on HIV testing, and home-based testing through HIV self-testing.

Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor associated cutaneous adverse drug reactions: A systematic review of case reports and case series.

Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse drug reactions (CADRs). However, there is limited information on the factors associated with these occurrences. In this study, we aimed to describe the demographic, clinical and pharmacological characteristics associated with CADRs encountered by patients administered SSRIs and/or SNRIs for psychiatric diagnoses and to compare the differences in these factors between severe and non-severe CADRs. A protocol was developed a priori (PROSPERO: CRD42020204830) in line with the PRISMA guidelines. We searched PubMed/Medline, PsycINFO and SCOPUS from inception to October 2020 to identify case reports and/or case series of SSRI and SNRI associated CADRs. Additional cases were obtained from the retrieved articles' bibliography. A total of 141 articles were included in the study, documenting 173 CADRs. Females accounted for 128 (74.0%) of the analysed CADRs. The median age of the cases was 42 IQR (27; 53) with no statistically significant differences in age between males and females (P = 0.542). A total of 157 (90.8%) of the reported CADRs were associated with SSRIs, particularly fluoxetine 68 (39.5%), sertraline 30 (17.4%) and paroxetine 25 (14.5%). Non-severe CADRs and severe CADRs accounted for 23 (13.4%) and 149 (86.6%) reports respectively. No statistically significant differences were observed for gender (P = 0.616), age at onset (P = 0.493) and time to onset (P = 0.105) between non-severe CADRs and SCARs. In conclusion, CADRs following SSRIs and SNRIs disproportionately affect females in the reproductive age group compared to males and are mostly associated with SSRIs.

Joint modelling of longitudinal and time-to-event data: an illustration using CD4 count and mortality in a cohort of patients initiated on antiretroviral therapy.

BACKGROUND: Modelling of longitudinal biomarkers and time-to-event data are important to monitor disease progression. However, these two variables are traditionally analyzed separately or time-varying Cox models are used. The former strategy fails to recognize the shared random-effects from the two processes while the latter assumes that longitudinal biomarkers are exogenous covariates, resulting in inefficient or biased estimates for the time-to-event model. Therefore, we used joint modelling for longitudinal and time-to-event data to assess the effect of longitudinal CD4 count on mortality. METHODS: We studied 4014 patients from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) who initiated ART between June 2004 and August 2013. We used proportional hazards regression model to assess the effect of baseline characteristics (excluding CD4 count) on mortality, and linear mixed effect models to evaluate the effect of baseline characteristics on the CD4 count evolution over time. Thereafter, the two analytical approaches were amalgamated to form an advanced joint model for studying the effect of longitudinal CD4 count on mortality. To illustrate the virtues of the joint model, the results from the joint model were compared to those from the time-varying Cox model. RESULTS: Using joint modelling, we found that lower CD4 count over time was associated with a 1.3-fold increase in the risk of death, (HR: 1.34, 95% CI: 1.27-1.42). Whereas, results from the time-varying Cox model showed lower CD4 count over time was associated with a 1.2-fold increase in the risk of death, (HR: 1.17, 95% CI: 1.12-1.23). CONCLUSIONS: Joint modelling enabled the assessment of the effect of longitudinal CD4 count on mortality while correcting for shared random effects between longitudinal and time-to-event models. In the era of universal test and treat, the evaluation of CD4 count is still crucial for guiding the initiation and discontinuation of opportunistic infections prophylaxis and assessment of late presenting patients. CD4 count can also be used when immunological failure is suspected as we have shown that it is associated with mortality.

Neuroquantification enhances the radiological evaluation of term neonatal hypoxic-ischaemic cerebral injuries.

Background: Injury patterns in hypoxic-ischaemic brain injury (HIBI) are well recognised but there are few studies evaluating cerebral injury using neuroquantification models. Objectives: Quantification of brain volumes in a group of patients with clinically determined cerebral palsy. Method: In this retrospective study, 297 children with cerebral palsy were imaged for suspected HIBI with analysis of various cerebral substrates. Of these, 96 children over the age of 3 years with a clinical diagnosis of cerebral palsy and abnormal MRI findings underwent volumetric analyses using the NeuroQuant® software solution. The spectrum of volumetric changes and the differences between the various subtypes (and individual subgroups) of HIBI were compared. Results: Compared with the available normative NeuroQuant® database, the average intracranial volume was reduced to the 1st percentile in all patient groups (p < 0.001). Statistically significant differences were observed among the types and subgroups of HIBI. Further substrate volume reductions were identified and described involving the thalami, brainstem, hippocampi, putamina and amygdala. The combined volumes of five regions of interest (frontal pole, putamen, hippocampus, brainstem and paracentral lobule) were consistently reduced in the Rolandic basal ganglia-thalamus (RBGT) subtype. Conclusion: This study determined a quantifiable reduction of intracranial volume in all subtypes of HIBI and predictable selective cerebral substrate volume reduction in subtypes and subgroups. In the RBGT subtype, a key combination of five substrate injuries was consistently noted, and thalamic, occipital lobe and brainstem volume reduction was also significant when compared to the watershed subtype. Contribution: This study demonstrates the value of integrating an artificial intelligence programme into the radiologists' armamentarium serving to quantify brain injuries more accurately in HIBI. Going forward this will be an inevitable evolution of daily radiology practice in many fields of medicine, and it would be beneficial for radiologists to embrace these technological innovations.

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial.

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19. Clinical Trial Registration: DOH-27-062021-9191 (South African National Clinical Trials Register).

Natural proteins found in milk (lactoferrin) and egg white (ovotransferrin and lysozyme) could have therapeutic value in COVID-19 through their effects on the immune system. We identified bovine colostrum and hen egg white powders containing adequate quantities of these proteins. We investigated whether short-term daily consumption of a hen egg white and bovine colostrum mixture (reconstituted with glycerin and water) could reduce the risk of progression to severe disease and assist in the recovery of patients with mild or moderate COVID-19. Adults with mild or moderate COVID-19 who were within 5 days of symptom onset and had risk factors for severe disease were enrolled, and randomly assigned to take a hen egg white and bovine colostrum mixture or placebo mixture twice daily for 5 days, and then followed up telephonically for 6 weeks. The main findings were that consumption of the hen egg white and bovine colostrum mixture was associated with fewer protocol-defined severe-type symptoms overall, and in particular lower frequencies of joint pain/malaise, chest pain, fever/chills, and sore throat. Only one individual developed severe COVID-19 and therefore the effect of the intervention on reducing the risk of progression to severe disease could not be assessed. The results of this study suggest that consumption of the hen egg white bovine colostrum mixture within a few days of symptom onset lessens symptoms in people with mild or moderate COVID-19.

A proposed magnetic resonance imaging grading system for the spectrum of central neonatal parasagittal hypoxic-ischaemic brain injury.

AIM: To describe the spectrum of parasagittal injury on MRI studies performed on children following severe perinatal term hypoxia-ischaemia, using a novel MRI grading system, and propose a new central pattern correlated with neuropathologic features. METHODS: MR scans of 297 patients with perinatal term hypoxia-ischaemia were evaluated for typical patterns of brain injury. A total of 83 patients that demonstrated the central/basal ganglia-thalamus and perirolandic pattern of injury were categorised according to the degree of severity. The perirolandic injury was graded by the degree of interhemispheric widening, paracentral lobule involvement and perirolandic cortex destruction leading to a tiered categorisation. Of these 83 patients, 19 had the most severe subtype of injury. A detailed analysis of the clinical data of a subset of 11 of these 19 patients was conducted. RESULTS: We demonstrated the mild subtype in 21/83(25%), the moderate subtype in 22/83(27%) and the severe subtype in 21/83(25%). A fourth pattern was identified in 19/83(23%) patients with a diamond-shaped expansion of the interhemispheric fissure, concomitant thalamic, putaminal, hippocampal and other smaller substrate involvement indicative of the most destructive subtype. CONCLUSIONS: We propose a new MR grading system of injury at the parasagittal perirolandic region related to severe, sustained central perinatal term hypoxia-ischaemia. We also introduce a previously undescribed pattern of injury, the most severe form of this spectrum, seen especially after prolongation of the second stage of labour. This constellation of high metabolic substrate, targeted tissue destruction is consistently demonstrated by MRI, termed the massive paramedian injury pattern.

Point-of-care CD4 testing: Differentiated care for the most vulnerable.

BACKGROUND: South Africa, with the highest burden of HIV infection globally, has made huge strides in its HIV/ART programme, but AIDS deaths have not decreased proportionally to ART uptake. Advanced HIV disease (CD4 < 200 cells/mm3) persists, and CD4 count testing is being overlooked since universal test-and-treat was implemented. Point-of-care CD4 testing could address this gap and assure differentiated care to these vulnerable patients with low CD4 counts. METHODS: A time randomised implementation trial was conducted, enrolling 603 HIV positive non-ART, not pregnant patients at a primary health care clinic in Durban, South Africa. Weeks were randomised to either point-of-care CD4 testing (n = 305 patients) or standard-of-care central laboratory CD4 testing (n = 298 patients) to assess the proportion initiating ART at 3 months. Cox regression, with robust standard errors adjusting for clustering by week, were used to assess the relationship between treatment initiation and arm. RESULTS: Among the 578 (299 point-of-care and 279 standard-of-care) patients eligible for analysis, there was no significant difference in the number of eligible patients initiating ART within 3 months in the point-of-care (73%) and the standard-of-care (68%) groups (P = 0.112). The time-to-treat analysis was not significantly different in patients with CD4 counts of 201-500 cells/mm3 which could have been due to appointment scheduling to cope with the large burden of cases. However, in patients with advanced HIV disease (CD4 < 200cells/mm3) 65% more patients started ART earlier in the point-of-care group (HR 1.65 (95% confidence interval (CI) = 0.99-2.75; P = 0.052) compared to the standard-of-care group. CONCLUSIONS: Point-of-care testing decreased time-to-treatment in those with advanced HIV disease. With universal test and treat for HIV, rollout of simple point-of-care CD4 testing would ensure early diagnosis of advanced HIV disease and facilitate differentiated care for these vulnerable patients as per the World Health Organisation 2020 target product profile for point-of-care CD4 testing. TRIAL REGISTRATION: ISRCTN14220457.

Mapping Evidence on the Burden of Breast, Cervical, and Prostate Cancers in Sub-Saharan Africa: A Scoping Review.

Background: Cancer remains a major public health problem, especially in Sub-Saharan Africa (SSA) where the provision of health care is poor. This scoping review mapped evidence in the literature regarding the burden of cervical, breast and prostate cancers in SSA. Methods: We conducted this scoping review using the Arksey and O'Malley framework, with five steps: identifying the research question; searching for relevant studies; selecting studies; charting the data; and collating, summarizing, and reporting the data. We performed all the steps independently and resolved disagreements through discussion. We used Endnote software to manage references and the Rayyan software to screen studies. Results: We found 138 studies that met our inclusion criteria from 2,751 studies identified through the electronic databases. The majority were retrospective studies of mostly registries and patient files (n = 77, 55.8%), followed by cross-sectional studies (n = 51, 36.9%). We included studies published from 1990 to 2021, with a sharp increase from 2010 to 2021. The quality of studies was overall satisfactory. Most studies were done in South Africa (n = 20) and Nigeria (n = 17). The majority were on cervical cancer (n = 93, 67.4%), followed by breast cancer (67, 48.6%) and the least were on prostate cancer (48, 34.8%). Concerning the burden of cancer, most reported prevalence and incidence. We also found a few studies investigating mortality, disability-adjusted life years (DALYs), and years of life lost (YLL). Conclusions: We found many retrospective record review cross-sectional studies, mainly in South Africa and Nigeria, reporting the prevalence and incidence of cervical, breast and prostate cancer in SSA. There were a few systematic and scoping reviews. There is a scarcity of cervical, breast and prostate cancer burden studies in several SSA countries. The findings in this study can inform policy on improving the public health systems and therefore reduce cancer incidence and mortality in SSA.

Genital and systemic immune effects of the injectable, contraceptive norethisterone enanthate (NET-EN), in South African women.

PROBLEM: Injectable hormonal contraceptives (IHC) have been associated with altered mucosal and systemic milieu which might increase HIV risk, but most studies have focused on DMPA and not NET-EN, despite the growing popularity and lower HIV risk associated with the latter in observational studies. METHOD OF STUDY: We used high-performance liquid chromatography in combination with tandem triple quadrupole mass spectrometry (HPLC-LC-MS/MS) to measure steroid hormones in plasma samples of CAPRISA004 study participants. Concentrations of 48 cytokines were measured in the cervicovaginal lavage (CVL) and plasma, and their expression was compared between participants with detectable NET-EN (n = 201) versus non-detectable IHC (n = 90). Each log10 cytokine concentration was tested as an outcome in linear-mixed models, with NET-EN detection as the main explanatory variable. Multivariable models were adjusted for potential confounders. RESULTS: In bivariate analysis, detectable NET-EN was associated with reduced cervicovaginal M-CSF (P = 0.008), GM-CSF (P = 0.025) and G-CSF (P = 0.039), and elevated levels MIF (P = 0.008), IL-18 (P = 0.011), RANTES (P = 0.005) and IL-1Rα (P < 0.001). Lower G-CSF (P = 0.011) and elevated IL-1Rα (P = 0.008) remained significant in adjusted models. Multivariable analyses of plasma samples obtained from NET-EN-detectable women showed a significant increase in IP-10 (P = 0.026) and reductions in TNF-ß (P = 0.037), RANTES (P = 0.009), and M-CSF (P < 0.001). While similar growth factor reduction in CVL was noted for both DMPA and NET-EN, similar trends were not observed for endogenous progesterone. CONCLUSIONS: Detectable NET-EN was associated with reduced growth factors in the plasma and genital tract; particularly G-CSF and M-CSF. Our results suggest that while NET-EN is not inflammatory, it may have important immunological effects.

The spectrum of electrolyte abnormalities in black African people living with human immunodeficiency virus and diabetes mellitus at Edendale Hospital, Pietermaritzburg, South Africa.

BACKGROUND: Serum electrolyte abnormalities in black African people living with human immunodeficiency virus (HIV) and diabetes mellitus (PLWH/DM) is unknown. OBJECTIVES: The aim of this study was to analyse serum electrolytes (sodium, potassium, calcium and phosphate) and factors associated with electrolyte abnormalities in black African PLWH/DM versus HIV-uninfected patients with DM. METHODS: We conducted a retrospective case-control study in 96 black African PLWH/DM (cases) and 192 HIV-uninfected patients with DM (controls), who were visiting the Edendale Hospital DM clinic, from 01 January 2016 to 31 December 2016. Pearson's correlation, multivariate linear and logistic regression analyses were utilised. RESULTS: Hypocalcaemia was the most frequent electrolyte abnormality in PLWH/DM and HIV-uninfected patients with DM (31.25% vs. 22.91%), followed by hyponatraemia (18.75% vs. 13.54%). Median (IQR) corrected serum calcium levels were significantly lower in PLWH/DM compared with HIV-uninfected patients with DM (2.24 [2.18-2.30] mmol/L vs. 2.29 [2.20-2.36] mmol/L; p = 0.001). For every per cent increase in glycated haemoglobin, the odds of hyponatraemia significantly increased in both PLWH/DM (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.19 -2.02; p = 0.003) and HIV-uninfected patients with DM (OR: 1.26; 95% CI: 1.04 -1.54; p = 0.009). CONCLUSION: Hypocalcaemia and hyponatraemia were the most frequent electrolyte abnormalities and occurred more frequently in PLWH/DM compared with HIV-uninfected patients with DM. People living with HIV and DM have significantly lower corrected serum calcium levels compared with HIV-uninfected patients with DM. Furthermore, hyponatraemia is a marker of impaired glycaemic control.

Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women.

Long-acting injectable contraceptives have been associated with mucosal immune changes and increased HIV acquisition, but studies have often been hampered by the inaccuracy of self-reported data, unknown timing of injection, and interactions with mucosal transmission co-factors. We used mass spectrometry to quantify the plasma concentrations of injectable contraceptives in women from the CAPRISA004 study (n = 664), with parallel quantification of 48 cytokines and >500 host proteins in cervicovaginal lavage. Higher DMPA levels were associated with reduced CVL concentrations of GCSF, MCSF, IL-16, CTACK, LIF, IL-1α, and SCGF-ß in adjusted linear mixed models. Dose-dependent relationships between DMPA concentration and genital cytokines were frequently observed. Unsupervised clustering of host proteins by DMPA concentration suggest that women with low DMPA had increases in proteins associated with mucosal fluid function, growth factors, and keratinization. Although DMPA was not broadly pro-inflammatory, DMPA was associated with increased IP-10 in HSV-2 seropositive and older women. DMPA-cytokine associations frequently differed by vaginal microbiome; in non-Lactobacillus-dominant women, DMPA was associated with elevated IL-8, MCP-1, and IP-10 concentrations. These data confirm a direct, concentration-dependant effect of DMPA on functionally important immune factors within the vaginal compartment. The biological effects of DMPA may vary depending on age, HSV-2 status, and vaginal microbiome composition.