Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia.

AIMS/HYPOTHESIS: We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations. METHODS: A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (n = 236, ≤35 years) and control participants (n = 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants. RESULTS: Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16-25 and 26-35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 (p = 0.0014) and HLA-DRB1*04 (p = 0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective (p < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (p = 1.60 × 10-7). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans. CONCLUSIONS/INTERPRETATION: The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.

Exploring patients' self-reported experiences of out-of-hours primary care and their suggestions for improvement: a qualitative study.

BACKGROUND AND OBJECTIVE: Out-of-hours services for primary care provision are increasing in policy relevance. The aim of this qualitative study was to explore service users' recent experiences of out-of-hours services and to identify suggestions for improvement for services and practitioners involved. METHODS: We used data from a cross-sectional survey of service users' self-reported experiences of 13 out-of-hours centres in Wales. Three hundred and forty-one respondents provided free-text comments focusing on suggestions for improvement within the survey instrument (the Out-of-hours Patient Questionnaire). A coding framework was based on previous literature focusing on patients' experiences of out-of-hours services, built upon and refined as it was systematically applied to the data. Emergent themes and subthemes were charted and interpreted to comprise the findings. RESULTS: Central themes emerged from users' perspectives of the structure of out-of-hours services, process of care and outcomes for users. Themes included long waiting times, perceived quality of service user-practitioner communication, consideration for parents and children and accessibility of the service and medication. Suggestions for improving care were made across these themes, including triaging patients more effectively and efficiently, addressing specific aspects of practitioners' communication with patients, reconsidering the size of areas covered by services and number of professionals required for the population covered, extending GP and pharmacy opening times and medication delivery services. CONCLUSIONS: It is important to consider ways to address service users' principal concerns surrounding out-of-hours services. Debate is required about prioritizing and implementing potential improvements to out-of-hours services in the light of resource constraints.

Missed opportunities for earlier treatment? A qualitative interview study with parents of children admitted to hospital with serious respiratory tract infections.

OBJECTIVE: To identify potential opportunities for earlier intervention among children who develop a complicated respiratory tract infection (RTI). DESIGN: Qualitative, face-to-face, individual interview study, either in hospital or at home, with parents of children admitted to hospital with a complicated RTI. SETTING: Participants were recruited from a large UK teaching hospital, and described events (largely) prior to hospital admission. PARTICIPANTS: Parents of 22 children (12 with empyema, 8 with pneumonia, 1 with peritonsillar abscess and 1 with mastoiditis). RESULTS: Parents' accounts revealed missed opportunities for timely treatment resulting from parental and health service associated factors. Themes relating to parental factors included problems assessing the severity of the illness (5 parents), beliefs about accessing health services (10 parents; including fear of appearing 'neurotic', belief that their concerns would not be taken seriously, and belief that their child would not be prescribed antibiotics or would be prescribed antibiotics too readily) and feeling powerless to challenge clinical authority (7 parents). Health service associated factors included perceived problems accessing healthcare services (13 parents; including inadequate primary care triage, barriers to accessing timely consultations and past experience of problems accessing healthcare leading to failure to consult) and perceived poor quality clinical encounters (11 parents; including inadequate assessment and communication). CONCLUSION: Addressing, where appropriate, these parental (skills, fears and beliefs) and health service (access and consultation quality) associated factors may lead to more prompt care for seriously ill children.