Victoria Simms

Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study

BACKGROUND Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. METHODS We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. FINDINGS 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. INTERPRETATION Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. FUNDING None.

Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial

BACKGROUND Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening. METHODS We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per μL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413. FINDINGS Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community support group than in standard care group (p=0·004). INTERPRETATION Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa. FUNDING European and Developing Countries Clinical Trials Partnership.

A national survey of musculoskeletal impairment in Rwanda: prevalence, causes and service implications.

Background Accurate information on the prevalence and causes of musculoskeletal impairment (MSI) is lacking in low income countries. We present a new survey methodology that is based on sound epidemiological principles and is linked to the World Health Organisations International Classification of Functioning. Methods Clusters were selected with probability proportionate to size. Households were selected within clusters through compact segment sampling. 105 clusters of 80 people (all ages) were included. All participants were screened for MSI by a physiotherapist and medical assistant. Possible cases plus a random sample of 10% of non-MSI cases were examined further to ascertain diagnosis, aetiology, quality of life, and treatment needs. Findings 6757 of 8368 enumerated individuals (80.8%) were screened. There were 352 cases, giving an overall prevalence for MSI of 5.2%. (95% CI 4.5–5.9) The prevalence of MSI increased with age and was similar in men and women. Extrapolating these estimates, there are approximately 488,000 MSI diagnoses in Rwanda. Only 8.2% of MSI cases were severe, while the majority were moderate (43.7%) or mild (46.3%). Diagnostic categories comprised 11.5% congenital, 31.3% trauma, 3.8% infection, 9.0% neurological, and 44.4% non-traumatic non infective acquired. The most common individual diagnoses were joint disease (13.3%), angular limb deformity (9.7%) and fracture mal- and non-union (7.2%). 96% of all cases required further treatment. Interpretation This survey demonstrates a large burden of MSI in Rwanda, which is mostly untreated. The survey methodology will be useful in other low income countries, to assist with planning services and monitoring trends.

Availability of essential drugs for managing HIV-related pain and symptoms within 120 PEPFAR-funded health facilities in East Africa: A cross-sectional survey with onsite verification.

Background: World Health Organization’s essential drugs list can control the highly prevalent HIV-related pain and symptoms. Availability of essential medicines directly influences clinicians’ ability to effectively manage distressing manifestations of HIV. Aim: To determine the availability of pain and symptom controlling drugs in East Africa within President’s Emergency Plan for AIDS Relief–funded HIV health care facilities. Design: Directly observed quantitative health facilities’ pharmacy stock review. We measured availability, expiration and stock-outs of specified drugs required for routine HIV management, including the World Health Organization pain ladder. Setting: A stratified random sample in 120 President’s Emergency Plan for AIDS Relief–funded HIV care facilities (referral and district hospitals, health posts/centres and home-based care providers) in Kenya and Uganda. Results: Non-opioid analgesics (73%) and co-trimoxazole (64%) were the most commonly available drugs and morphine (7%) the least. Drug availability was higher in hospitals and lower in health centres, health posts and home-based care facilities. Facilities generally did not use minimum stock levels, and stock-outs were frequently reported. The most common drugs had each been out of stock in the past 6 months in 47% of facilities stocking them. When a minimum stock level was defined, probability of a stock-out in the previous 6 months was 32.6%, compared to 45.5% when there was no defined minimum stock level (χ2 = 5.07, p = 0.024). Conclusion: The data demonstrate poor essential drug availability, particularly analgesia, limited by facility type. The lack of strong opioids, isoniazid and paediatric formulations is concerning. Inadequate drug availability prevents implementation of simple clinical pain and symptom control protocols, causing unnecessary distress. Research is needed to identify supply chain mechanisms that lead to these problems.

Household pit latrines as a potential source of the fly Musca sorbens -- a one year longitudinal study from The Gambia.

Objectives  To assess whether the trachoma vector Musca sorbens was breeding in household latrines in a trachoma‐endemic part of The Gambia.

Prevalence of epilepsy in Rwanda: a national cross-sectional survey.

Objective  To estimate the prevalence of epilepsy in Rwanda, as part of a survey of musculoskeletal impairment (MSI).

Poverty and musculoskeletal impairment in Rwanda

The recently adopted UN Convention on the Rights of Persons with Disabilities acknowledges the need to address social exclusion and poverty of persons with disabilities. However, policy makers, especially in low-income countries, often lack information about the socioeconomic situation of this vulnerable group of society. This study aimed to assess the association between poverty and musculoskeletal impairment (MSI) in Rwanda. A nationwide population-based matched case-control study was undertaken in Rwanda. Data were collected on education, literacy, employment, household expenditure and assets for 345 cases and 532 matched controls. Conditional logistic regression was performed, and the results indicated that adults with MSI in Rwanda are more likely to have no employment (odds ratio (OR)=3.3, 95% CI 2.1-5.2) while children with MSI are less likely to attend school (OR=0.4, 95% CI 0.2-0.9). Cases with MSI are disadvantaged vis-à-vis housing conditions and household size, potentially indicating crowding. However, cases with MSI were not poorer than controls in terms of assets or expenditure. These data suggest that increased efforts should be undertaken in Rwanda in order to ensure that children with disabilities are included in schools and that adults with disabilities can find appropriate employment opportunities.

How to analyze palliative care outcome data for patients in Sub-Saharan Africa: an international, multicenter, factor analytic examination of the APCA African POS.

CONTEXT The incidence of life-limiting progressive disease in sub-Saharan Africa presents a significant clinical and public health challenge. The ability to easily measure patient outcomes is essential to improving care. OBJECTIVES The present study aims to determine the specific factors (if any) that underpin the African Palliative Care Association African Palliative Outcome Scale to assist the analysis of data in routine clinical care and audit. METHODS Using self-reported data collected from patients with HIV infection in eastern and southern Africa, an exploratory factor analysis was undertaken with 1337 patients; subsequently, a confirmatory analysis was done on two samples from separate data sets (n = 445). RESULTS Using exploratory factor analysis initially, both two- and three-factor solutions were examined and found to meet the criteria for simple structure and be readily interpretable. Then using confirmatory factor analysis on two separate samples, the three-factor solution demonstrated better fit, with Goodness-of-Fit Index values greater than 0.95 and Normative Fit Index values close to 0.90. The resulting three factors were 1) physical and psychological well-being, 2) interpersonal well-being, and 3) existential well-being. CONCLUSION This analysis presents an important new opportunity in the analysis of outcome data for patients with progressive disease. It has advantages over both the total scoring of multidimensional scaling (which masks differences between domains) and of item scoring (which requires repeated analyses). The three factors map well onto the underlying concept and clinical goals of palliative care, and will enable audit of facility care.

Treatment outcomes in palliative care: the TOPCare study. A mixed methods phase III randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy

BackgroundPatients with HIV/AIDS on Antiretroviral Therapy (ART) suffer from physical, psychological and spiritual problems. Despite international policy explicitly stating that a multidimensional approach such as palliative care should be delivered throughout the disease trajectory and alongside treatment, the effectiveness of this approach has not been tested in ART-experienced populations.Methods/designThis mixed methods study uses a Randomised Controlled Trial (RCT) to test the null hypothesis that receipt of palliative care in addition to standard HIV care does not affect pain compared to standard care alone. An additional qualitative component will explore the mechanism of action and participant experience. The sample size is designed to detect a statistically significant decrease in reported pain, determined by a two tailed test and a p value of ≤0.05. Recruited patients will be adults on ART for more than one month, who report significant pain or symptoms which have lasted for more than two weeks (as measured by the African Palliative Care Association (APCA) African Palliative Outcome Scale (POS)). The intervention under trial is palliative care delivered by an existing HIV facility nurse trained to a set standard. Following an initial pilot the study will be delivered in two African countries, using two parallel independent Phase III clinical RCTs. Qualitative data will be collected from semi structured interviews and documentation from clinical encounters, to explore the experience of receiving palliative care in this context.DiscussionThe data provided by this study will provide evidence to inform the improvement of outcomes for people living with HIV and on ART in Africa.ClinicalTrials.gov Identifier: NCT01608802

Multi-centred mixed-methods PEPFAR HIV care & support public health evaluation: study protocol

BackgroundA public health response is essential to meet the multidimensional needs of patients and families affected by HIV disease in sub-Saharan Africa. In order to appraise curret provision of HIV care and support in East Africa, and to provide evidence-based direction to future care programming, and Public Health Evaluation was commissioned by the PEPFAR programme of the US Government.Methods/DesignThis paper described the 2-Phase international mixed methods study protocol utilising longitudinal outcome measurement, surveys, patient and family qualitative interviews and focus groups, staff qualitative interviews, health economics and document analysis.Aim 1) To describe the nature and scope of HIV care and support in two African countries, including the types of facilities available, clients seen, and availability of specific components of care [Study Phase 1]. Aim 2) To determine patient health outcomes over time and principle cost drivers [Study Phase 2].The study objectives are as follows. 1) To undertake a cross-sectional survey of service configuration and activity by sampling 10% of the facilities being funded by PEPFAR to provide HIV care and support in Kenya and Uganda (Phase 1) in order to describe care currently provided, including pharmacy drug reviews to determine availability and supply of essential drugs in HIV management. 2) To conduct patient focus group discussions at each of these (Phase 1) to determine care received. 3) To undertake a longitudinal prospective study of 1200 patients who are newly diagnosed with HIV or patients with HIV who present with a new problem attending PEPFAR care and support services. Data collection includes self-reported quality of life, core palliative outcomes and components of care received (Phase 2). 4) To conduct qualitative interviews with staff, patients and carers in order to explore and understand service issues and care provision in more depth (Phase 2). 5) To undertake document analysis to appraise the clinical care procedures at each facility (Phase 2). 6) To determine principle cost drivers including staff, overhead and laboratory costs (Phase 2).DiscussionThis novel mixed methods protocol will permit transparent presentation of subsequent dataset results publication, and offers a substantive model of protocol design to measure and integrate key activities and outcomes that underpin a public health approach to disease management in a low-income setting.