CRP (C-Reactive Protein) in Outcome Prediction After Subarachnoid Hemorrhage and the Role of Machine Learning.

Background and Purpose: Outcome prediction after aneurysmal subarachnoid hemorrhage (aSAH) is challenging. CRP (C-reactive protein) has been reported to be associated with outcome, but it is unclear if this is independent of other predictors and applies to aSAH of all grades. Therefore, the role of CRP in aSAH outcome prediction models is unknown. The purpose of this study is to assess if CRP is an independent predictor of outcome after aSAH, develop new prognostic models incorporating CRP, and test whether these can be improved by application of machine learning. Methods: This was an individual patient-level analysis of data from patients within 72 hours of aSAH from 2 prior studies. A panel of statistical learning methods including logistic regression, random forest, and support vector machines were used to assess the relationship between CRP and modified Rankin Scale. Models were compared with the full Subarachnoid Hemmorhage International Trialists' (SAHIT) prediction tool of outcome after aSAH and internally validated using cross-validation. Results: One thousand and seventeen patients were included for analysis. CRP on the first day after ictus was an independent predictor of outcome. The full SAHIT model achieved an area under the receiver operator characteristics curve (AUC) of 0.831. Addition of CRP to the predictors of the full SAHIT model improved model performance (AUC, 0.846, P=0.01). This improvement was not enhanced when learning was performed using a random forest (AUC, 0.807), but was with a support vector machine (AUC of 0.960, P <0.001). Conclusions: CRP is an independent predictor of outcome after aSAH. Its inclusion in prognostic models improves performance, although the magnitude of improvement is probably insufficient to be relevant clinically on an individual patient level, and of more relevance in research. Greater improvements in model performance are seen with support vector machines but these models have the highest classification error rate on internal validation and require external validation and calibration.

HIV and tuberculosis in prisons in sub-Saharan Africa.

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

The physiological effect of a 'climb assist' device on vertical ladder climbing.

'Climb assist' claims to reduce strain when climbing ladders; however, no research has yet substantiated this. The purpose of this study was to assess the physiological and psychophysical effects of climb assist on 30 m ladder climbing at a minimum acceptable speed. Eight participants (six male and two female) climbed a 30 m ladder at 24 rungs per minute with and without climb assist, and were monitored for heart rate (HR), [Formula: see text]O2 and rate of perceived exertion (RPE). All three variables decreased significantly (p < 0.05) with climb assist with [Formula: see text]O2 decreasing by 22.5%, HR by 14.8% and RPE decreasing by a mean of 2.3 units on the 10-point Borg scale. When descending the ladder [Formula: see text]O2 decreased by a mean of 42% compared to that ascending. At the minimal acceptable climbing speed climb assist decreases the physiological strain on climbers, as demonstrated by reduced [Formula: see text]O2, HR and perceived exertion. Practitioner Summary: 'Climb assist' systems claim to reduce strain when climbing, however; no research has yet been published to substantiate this. A crossover study compared [Formula: see text]O2, HR and RPE at a minimal acceptable climbing speed with and without climb assist. Climb assist significantly reduced all variables confirming it reduces strain when climbing.

A Political and Social History of HIV in South Africa.

For the past 25 years, South Africa has had to deal with the inexorable and monumental rise of HIV. From one or two isolated cases, in the late 1980s, South Africa now has an estimated 6.4 million people infected with HIV, with high rates of concomitant tuberculosis, which will profoundly affect the country for decades to come. For nearly 10 years, the South African government's response to the HIV epidemic was described as denialist, which was estimated to have resulted in the deaths of 330,000 people because lifesaving antiretroviral therapy (ART) was not provided (Chigwedere et al. J Acquir Immune Defic Syndr. 49:410-15, 2008; Heywood 2004). However, the story of the HIV and AIDS response in South Africa over the past 5 years is one of great progress after almost a decade of complex and tragic denialism that united civil society in a way not seen since the opposition to apartheid. Today, South Africa can boast of close to 3 million people on ART, by far the largest number in the world. Prevention efforts appear to be yielding results but there continues to be large numbers of new infections, with a profound peak in incidence in young women aged 15 to 24 years. In addition, infections occur across the gender spectrum in older age groups. As a result of the massive increase in access to ART after 2004 and particularly after 2008 as political will towards the HIV ART programme improved, there has been a marked increase in life expectancy, from 56 to 61 years in the period 2009-2012 alone; the aggressive expansion of the prevention of mother to child transmission (PMTCT) to HIV-positive pregnant women has been accompanied by dramatic decrease in HIV transmission to infants; and a 25 % decrease in child and infant mortality rates in the period 2009-2012. This progress in access is significantly due to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

HIV programme sustainability in Southern and Eastern Africa and the changing role of external assistance for health.

High human immunodeficiency virus (HIV)-prevalence countries in Southern and Eastern Africa continue to receive substantial external assistance (EA) for HIV programming, yet countries are at risk of transitioning out of HIV aid without achieving epidemic control. We sought to address two questions: (1) to what extent has HIV EA in the region been programmed and delivered in a way that supports long-term sustainability and (2) how should development agencies change operational approaches to support long-term, sustainable HIV control? We conducted 20 semi-structured key informant interviews with global and country-level respondents coupled with an analysis of Global Fund budget data for Malawi, Uganda, and Zambia (from 2017 until the present). We assessed EA practice along six dimensions of sustainability, namely financial, epidemiological, programmatic, rights-based, structural and political sustainability. Our respondents described HIV systems' vulnerability to donor departure, as well as how development partner priorities and practices have created challenges to promoting long-term HIV control. The challenges exacerbated by EA patterns include an emphasis on treatment over prevention, limiting effects on new infection rates; resistance to service integration driven in part by 'winners' under current EA patterns and challenges in ensuring coverage for marginalized populations; persistent structural barriers to effectively serving key populations and limited capacity among organizations best positioned to respond to community needs; and the need for advocacy given the erosion of political commitment by the long-term and substantive nature of HIV EA. Our recommendations include developing a robust investment case for primary prevention, providing operational support for integration processes, investing in local organizations and addressing issues of political will. While strategies must be locally crafted, our paper provides initial suggestions for how EA partners could change operational approaches to support long-term HIV control and the achievement of universal health coverage.

Systematic hand-held echocardiography in patients hospitalized with acute coronary syndrome.

AIMS: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy, and time efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting. METHODS AND RESULTS: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiographies with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated. Overall, 262 patients (65 ± 12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiographies was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7 ± 1.6 min) and completed a median of 5 (interquartile range 3-20) h earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50%, and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making, and transthoracic echocardiography was no longer deemed necessary. CONCLUSION: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied, and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population and providing an evidence base for current guidelines.

Eliminating mother-to-child HIV transmission in South Africa.

PROBLEM: The World Health Organization has produced clear guidelines for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). However, ensuring that all PMTCT programme components are implemented to a high quality in all facilities presents challenges. APPROACH: Although South Africa initiated its PMTCT programme in 2002, later than most other countries, political support has increased since 2008. Operational research has received more attention and objective data have been used more effectively. LOCAL SETTING: In 2010, around 30% of all pregnant women in South Africa were HIV-positive and half of all deaths in children younger than 5 years were associated with the virus. RELEVANT CHANGES: Between 2008 and 2011, the estimated proportion of HIV-exposed infants younger than 2 months who underwent routine polymerase chain reaction (PCR) tests to detect early HIV transmission increased from 36.6% to 70.4%. The estimated HIV transmission rate decreased from 9.6% to 2.8%. Population-based surveys in 2010 and 2011 reported transmission rates of 3.5% and 2.7%, respectively. LESSONS LEARNT: CRITICAL ACTIONS FOR IMPROVING PROGRAMME OUTCOMES INCLUDED: ensuring rapid implementation of changes in PMTCT policy at the field level through training and guideline dissemination; ensuring good coordination with technical partners, such as international health agencies and international and local nongovernmental organizations; and making use of data and indicators on all aspects of the PMTCT programme. Enabling health-care staff at primary care facilities to initiate antiretroviral therapy and expanding laboratory services for measuring CD4+ T-cell counts and for PCR testing were also helpful.

Résumé PROBLÈME: L'Organisation mondiale de la Santé a élaboré des lignes directrices claires pour la prévention de la transmission mère-enfant (PTME) du virus de l'immunodéficience humaine (VIH). S'assurer que tous les éléments du programme de PTME soient mis en œuvre de manière qualitative dans tous les établissements présente cependant des défis. APPROCHE: Bien que l'Afrique du Sud ait lancé son programme de PTME en 2002, plus tard que la plupart des autres pays, le soutien politique a augmenté depuis 2008. La recherche opérationnelle a reçu davantage d'attention, et les données objectives ont été utilisées plus efficacement. ENVIRONNEMENT LOCAL: En 2010, environ 30% de toutes les femmes enceintes en Afrique du Sud étaient séropositives, et la moitié de tous les décès d'enfants de moins de 5 ans étaient associée au virus. CHANGEMENTS SIGNIFICATIFS: Entre 2008 et 2011, la proportion estimée de nourrissons de moins de 2 mois exposés au VIH, ayant subi une réaction en chaîne par polymérase (PCR) de routine visant à détecter la transmission précoce du VIH, est passée de 36,6% à 70,4%. Le taux estimé de transmission du VIH a diminué, passant de 9,6% à 2,8%. Les enquêtes basées sur la population en 2010 et 2011 ont signalé des taux de transmission de 3,5% et 2,7%, respectivement. LEÇONS TIRÉES: Voici certaines actions essentielles pour améliorer les résultats du programme: assurer la mise en œuvre rapide des changements de politique de PTME sur le terrain, grâce à la formation et à la diffusion des lignes directrices; assurer une bonne coordination avec les partenaires techniques, comme les agences de santé internationales et locales et les organisations non gouvernementales; et utiliser les données et les indicateurs relatifs à tous les aspects du programme de PTME. Il est aussi utile de permettre au personnel soignant des établissements de soins de santé primaires d'initier un traitement antirétroviral et de développer les services de laboratoire pour les décomptes de cellules CD4 + T et les tests PCR.

Resumen SITUACIÓN: La Organización Mundial de la Salud ha presentado unas directrices claras para la prevención de la transmisión del virus de la inmunodeficiencia humana (VIH) de la madre al niño. No obstante, habrá que superar algunos desafíos para asegurar la puesta en marcha de todos los elementos del programa de prevención a fin de alcanzar un nivel de calidad elevado en todas las instalaciones. ENFOQUE: Aunque Sudáfrica inició su programa de prevención en el año 2002, más tarde que la mayoría de los países, el apoyo político ha aumentado desde 2008. Se ha prestado más atención a las investigaciones operativas y los datos objetivos se han utilizado con mayor eficacia. MARCO REGIONAL: En 2010, alrededor del 30% de las mujeres embarazadas en Sudáfrica eran seropositivas, y la mitad de todas las muertes en niños menores de cinco años estuvieron asociadas al virus. CAMBIOS IMPORTANTES: Entre los años 2008 y 2011, la proporción estimada de niños menores de dos meses expuestos al VIH que se sometió a las pruebas rutinarias de reacción en cadena de la polimerasa aumentó del 36,6% al 70,4%, y la tasa estimada de transmisión del VIH se redujo del 9,6% al 2,8%. Las encuestas de población de los años 2010 y 2011 reflejaron unas tasas de transmisión del 3,5% y el 2,7%, respectivamente LECCIONES APRENDIDAS: Las actividades fundamentales para mejorar los resultados del programa incluyeron: garantizar la implementación rápida de los cambios en la política de prevención de la transmisión a nivel de campo mediante cursos formativos y la difusión de las directrices; garantizar una coordinación adecuada entre los socios técnicos, tales como las agencias sanitarias internacionales y las ONG locales e internacionales; y utilizar los datos e indicadores acerca de todos los aspectos del programa de prevención de la transmisión del VIH de la madre al niño. También resultó muy útil permitir al personal sanitario de los centros de atención primaria iniciar terapias antirretrovirales y ampliar los servicios de laboratorio para realizar los recuentos de linfocitos T CD4+ y las pruebas de reacción en cadena de la polimerasa.

Investigating the quality of HIV rapid testing practices in public antenatal health care facilities, South Africa.

Monitoring HIV prevalence using antenatal HIV sentinel surveillance is important for efficient epidemic tracking, programme planning and resource allocation. HIV sentinel surveillance usually employs unlinked anonymous HIV testing which raises ethical, epidemiological and public health challenges in the current era of universal test and treat. The World Health Organization (WHO) recommends that countries should consider using routine prevention of mother-to-child transmission of HIV (PMTCT) data for surveillance. We audited antenatal care clinics to assess the quality of HIV rapid testing practices as the first step to assess whether South Africa is ready to utilize PMTCT programme data for antenatal HIV surveillance. In 2017, we conducted a cross-sectional survey in 360 randomly sampled antenatal care clinics using the adapted WHO Stepwise-Process-for-Improving-the-Quality-of-HIV-Rapid-Testing (SPI-RT) checklist. We calculated median percentage scores within a domain (domain-specific median score), and across all domains (overall median percentage scores). The latter was used to classify sites according to five implementation levels; (from 0:<40% to 4: 90% or higher). Of 346 (96.1%) facilities assessed, an overall median percentage score of 62.1% (inter-quartile range (IQR): 50.8-71.9%) was obtained. The lowest domain-specific median percentage scores were obtained under training/certification (35% IQR: 10.0-50.0%) and external quality assurance (12.5% IQR: 0.0-50.0%), respectively. The majority (89%) of sites had an overall median score at level 2 or below; of these, 37% required improvement in specific areas and 6.4% in all areas. Facilities in districts implementing the HIV Rapid Test Quality Improvement Initiative and supported by the President's Emergency Plan for AIDS Relief (PEPFAR) had significantly higher median overall scores (65.6% IQR: 53.9-74.2%) (P-value from rank sum test: <0.001) compared with non-PEPFAR-supported facilities (56.6% IQR:47.7-66.0%). We found sub-optimal implementation of HIV rapid testing practices. We recommend the expansion of the PEPFAR-funded Rapid Test Continuous Quality Improvement (RTCQI) support to all antenatal care testing sites.

Avoiding the Road to Nowhere: Policy Insights on Scaling up and Sustaining Digital Health.

Digital health solutions offer tremendous potential to enhance the reach and quality of health services and population-level outcomes in low- and middle-income countries (LMICs). While the number of programs reaching scale increases yearly, the long-term sustainability for most remains uncertain. In this article, as researchers and implementors, we draw on experiences of designing, implementing and evaluating digital health solutions at scale in Africa and Asia, and provide examples from India and South Africa to illustrate ten considerations to support scale and sustainability of digital health solutions in LMICs. Given the investments being made in digital health solutions and the urgent concurrent needs to strengthen health systems to ensure their responsiveness to marginalized populations in LMICs, we cannot afford to go down roads that 'lead to nowhere'. These ten considerations focus on drivers of equity and innovation, the foundations for a digital health ecosystem, and the elements for systems integration. We urge technology enthusiasts to consider these issues before and during the roll-out of large-scale digital health initiatives to navigate the complexities of achieving scale and enabling sustainability.

Recent HIV infection among pregnant women in the 2017 antenatal sentinel cross-sectional survey, South Africa: Assay-based incidence measurement.

INTRODUCTION: New HIV infection during pre-conception and pregnancy is a significant contributor of mother-to-child transmission of HIV in South Africa. This study estimated HIV incidence (defined as new infection within the last one year from the time of the survey which included both new infections occurred during pregnancy or just before pregnancy) among pregnant women and described the characteristics of recently infected pregnant women at national level. METHODS: Between 1 October and 15 November 2017, we conducted a national cross-sectional survey among pregnant women aged 15-49 years old attending antenatal care at 1,595 public facilities. Blood specimens were collected from pregnant women and tested for HIV in a centralised laboratory. Plasma viral load and Limiting Antigen Avidity Enzyme Immunosorbent Assay (LAg) tests were further performed on HIV positive specimens to differentiate between recent and long-term infections. Recent infection was defined as infection that occurred within one year from the date of collection of blood specimen for the survey. Data on age, age of partner, and marital status were collected through interviews. Women whose specimens were classified as recent by LAg assay and with viral loads >1,000 copies/mL were considered as recently infected. The calculated proportion of HIV positive women with recent infection was adjusted for assay-specific parameters to estimate annual incidence. Survey multinomial logistic regression was used to examine factors associated with being recently infected using HIV negative women as a reference group. Age-disparate relationship was defined as having a partner 5 or more years older. RESULTS: Of 10,049 HIV positive participants with LAg and viral load data, 1.4% (136) were identified as recently infected. The annual HIV incidence was 1.5% (95% confidence interval (CI): 1.2-1.7). In multivariable analyses, being single (adjusted odds ratio, aOR: 3.4, 95% CI: 1.8-6.2) or cohabiting (aOR: 3.8, 95% CI: 1.8-7.7), compared to being married as well as being in an age-disparate relationship among young women (aOR: 3.1, 95% CI: 2.0-4.7; reference group: young women (15-24years) whose partners were not 5 years or more older) were associated with higher odds of recent infection. CONCLUSIONS: Compared to previous studies among pregnant women, the incidence estimated in this study was substantially lower. However, the UNAIDS target to reduce incidence by 75% by 2020 (which is equivalent to reducing incidence to <1%) has not been met. The implementation of HIV prevention and treatment interventions should be intensified, targeting young women engaged in age-disparate relationship and unmarried women to fast track progress towards the UNAIDS target.