Multiple levels of influence affecting the utilisation of adult asthma services in the private sector in Khartoum

Background Asthma is the third most common cause of hospital visits in Sudan and globally affects more than 300 million people (WHO, 2007) (IUATLD, 2011, 2018). Sudan has a pluralistic health care system with a strong and varied private sector and a three- tiered public health sector (federal, state and district). Most asthma patients in Sudan seek asthma care in hospital emergency rooms or in the private sector. The main constraints of the asthma services in the public sector are lack of resources, lack of medical doctors in certain areas, inconsistent drug supplies and an absence of community involvement in health affairs (Ebrahim et al., 2017). While there has been research examining the low availability of asthma services in the public sector in Sudan (El Sony et al., 2013), very little is known about which asthma services are available in the private sector. Objective The goal of this thesis was to use a mixed method approach to understand the utilisation of adult asthma services in the private sector in Khartoum. Design The research design was constructed using an explanatory sequential mixed method Social Ecological approach (Creswell, 2013). This approach was used to examine the influencing factors of asthma service utilisation in the private sector by considering the five nested, hierarchical levels: individual, familial/interpersonal, community, organisational, and policy/enabling environment. The quantitative research was conducted using a health facility survey of private hospitals, private chest clinics, and pharmacies, in order to describe the asthma services available. This was followed by qualitative research using in-depth interviews with asthma patients who use the private sector, to explore decision-making around facility use and asthma health care seeking behaviour in more detail. Findings The quantitative survey found low rates of spirometers and peak flow meters were available in private hospitals (28% and 33%, respectively). There was very little asthma-specific training for providers and little use of asthma treatment cards and registers. However, the qualitative interviews found that the quality of care in the private sector was viewed as better than in the public sector, with shorter waiting times and better hygiene levels. Patients sought frequent, short-term care at private facilities for acute attacks (predominately in hospital emergency rooms) rather than long-term management of their condition as outpatients. The severity of the disease and the major impact it had, particularly on younger adults’ lives, was striking. Stigma and misconceptions about the disease by the community was expressed strongly particularly by younger women and altered how they sought care and how they interacted with people in their social network and beyond. Conclusion The Social Ecological approach facilitated an in depth understanding of the barriers and enablers of effective care. Effective asthma case management requires input at all levels of service provision: inclusive health policy and government commitment, high quality service delivery, an uninterrupted affordable drug supply, community involvement in care and patient empowerment. Encouraging stakeholders across the different levels of influence to implement this holistic model of asthma case management across both the public and private sector has the potential to lead to a reduction in emergency room admissions, less severe asthma attacks, a reduction in asthma related stigma and less fear of social rejection and concern for the patients

Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of >35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences

Improving access to effective care for people with chronic respiratory symptoms in low and middle income countries.

Chronic respiratory symptoms are amongst the most common complaints among low and middle-income country (LMICs) populations and they are expected to remain common over the 10 to 20 year horizon. The underlying diseases (predominantly chronic obstructive pulmonary disease, asthma and tuberculosis) cause, and threaten to increasingly cause, substantial morbidity and mortality. Effective treatment is available for these conditions but LMICs health systems are not well set up to provide accessible clinical diagnostic pathways that lead to sustainable and affordable management plans especially for the chronic non communicable respiratory diseases. There is a need for clinical and academic capacity building together with well-conducted health systems research to underpin health service strengthening, policy and decision-making. There is an opportunity to integrate solutions for improving access to effective care for people with chronic respiratory symptoms with approaches to tackle other major population health issues that depend on well-functioning health services such as chronic communicable (e.g. HIV) and non-communicable (e.g. cardiovascular and metabolic) diseases

Stronger together: evidence for collaborative action on neglected tropical diseases

This editorial has been written by programme leads at the Liverpool School of Tropical Medicine in the UK to condense the learning shared across articles. Articles within this supplement have been written and led by authors in Nigeria and Liberia, and informed by learnings from across the partnership including from our partners in Ghana and Cameroon and articles previously published. Early career researchers were supported throughout the COUNTDOWN programme to publish evidence and lead the production of impactful papers. Decision makers and local implementers from each context are also authors on the papers within the supplement and were supported to engage with the writing process

Risk factors of ischemic stroke and subsequent outcome in hemodialysis patients

Background and purpose: End stage renal disease (ESRD) requiring hemodialysis (HD) carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge concerning risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. Methods: All adult patients receiving HD for ESRD from 01/01/2007 to 31/12/2012 were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging and dialysis related variables were assessed and case-fatality determined. Follow-up was until 31/12/2013. Results: 1382 patients were identified (mean age 60.5 years, 58.5% male). The prevalence of AF was 21.2% and 59.4% were incident HD patients. 160 (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident HD patients. Factors associated with stroke on regression analysis were prior stroke, diabetes and age at starting renal replacement therapy. AF was not significantly associated with stroke and warfarin did not affect stroke risk in warfarin treated patients. Fatality was 18.8% at 7, 26.9% at 28 and 56.3% 365 days after stroke.<p></p> Conclusions: Incidence of stroke is high in patients with ESRD on HD with high case-fatality. Incident HD patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving HD

Access to health care for people with disabilities in rural Malawi: what are the barriers?

Background People with disabilities experience significant health inequalities. In Malawi, where most individuals live in low-income rural settings, many of these inequalities are exacerbated by restricted access to health care services. This qualitative study explores the barriers to health care access experienced by individuals with a mobility or sensory impairment, or both, living in rural villages in Dowa district, central Malawi. In addition, the impact of a chronic lung condition, alongside a mobility or sensory impairment, on health care accessibility is explored. Methods Using data from survey responses obtained through the Research for Equity And Community Health (REACH) Trust’s randomised control trial in Malawi, 12 adult participants, with scores of either 3 or 4 in the Washington Group Short Set (WGSS) questions, were recruited. The WGSS questions concern a person’s ability in core functional domains (including seeing, hearing and moving), and a score of 3 indicates ‘a lot of difficulty’ whilst 4 means ‘cannot do at all’. People with cognitive impairments were not included in this study. All who were selected for the study participated in an individual in-depth interview and full recordings of these were then transcribed and translated. Results Through thematic analysis of the transcripts, three main barriers to timely and adequate health care were identified: 1) Cost of transport, drugs and services, 2) Insufficient health care resources, and 3) Dependence on others. Attitudinal factors were explored and, whilst unfavourable health seeking behaviour was found to act as an access barrier for some participants, community and health care workers’ attitudes towards disability were not reported to influence health care accessibility in this study. Conclusions This study finds that health care access for people with disabilities in rural Malawi is hindered by closely interconnected financial, practical and social barriers. There is a clear requirement for policy makers to consider the challenges identified here, and in similar studies, and to address them through improved social security systems and health system infrastructure, including outreach services, in a drive for equitable health care access and provision

Community drug distributors for mass drug administration in neglected tropical disease programmes: systematic review and analysis of policy documents

Background Mass drug administration (MDA) programmes for neglected tropical diseases (NTDs) depend on voluntary community drug distributors (CDDs) to deliver drugs, and these volunteer schemes need regular training and supervision. NTD policy now includes integration of multiple disease programmes, but we are unsure if there is clarity in what is currently expected of CDDs and how they are managed. We therefore analysed World Health Organization (WHO) policy, strategy and implementation guidance, and select national NTD programme implementation plans. Methods Included are a) WHO global and WHO-Regional Office for Africa guidelines, strategies, operational manuals and meeting reports published between January 2007 to February 2018 that included policy and plans for CDDs; and b) national NTD programme master plans for Cameroon, Ghana, Liberia and Nigeria. For both review components, we examined the CDD responsibilities through a framework developed iteratively against the documents and prepared a narrative synthesis. Results Twenty WHO policy documents met the inclusion criteria. In the twelve global and eight regional documents, the CDD role was not explicitly or comprehensively defined. Three documents mentioned CDDs will distribute drugs; some mentioned health promotion, data handling and engagement in clinical care. Four WHO documents noted a need for CDD training or management, eight detailed some aspect of this, and one regional document provided a comprehensive overview. In the national plans, additional responsibilities included case management in two countries and transmission control in two countries. Every plan included training and supervision, but this was not always explicit, and details of the purpose and frequency varied. In all national plans, CDD motivation was identified as a challenge but not comprehensively addressed, although one document mentioned provision of bicycles. Conclusions WHO and national policies and plans assume CDDs will implement NTD programmes. However, there is almost no clear delineation of responsibilities, nor is there up-to-date practical guidance to guide managers. This ambiguity, in relation to the lack of explicit policies or programmatic guidance, probably impairs the effectiveness of NTD programmes

Survival of motor neurone protein is required for normal postnatal development of the spleen

Funding S.H.P. received an Anatomical Society PhD Studentship award for A.K.T. T.H.G. received an Anatomical Society PhD Studentship award for R.A.P. and funding from the SMA Trust (UK SMA Research Consortium), Euan MacDonald Centre for Motor Neurone Disease Research, and Muscular Dystrophy UK. K.J.S received funding for pathologic studies in human subjects from NICHD grant R01-HD054599.Peer reviewedPostprin

Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

Acknowledgments Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).Peer reviewedPublisher PD