Principles for task shifting hypertension and diabetes screening and referral: a qualitative study exploring patient, community health worker and healthcare professional perceptions in rural Uganda.

BACKGROUND: A shortage of healthcare workers in low- and middle-income countries (LMICs) combined with a rising burden of non-communicable diseases (NCDs) like hypertension and diabetes mellitus has resulted in increasing gaps in care delivery for NCDs. As community health workers (CHWs) often play an established role in LMIC healthcare systems, these programs could be leveraged to strengthen healthcare access. The objective of this study was to explore perceptions of task shifting screening and referral for hypertension and diabetes to CHWs in rural Uganda. METHODS: This qualitative, exploratory study was conducted in August 2021 among patients, CHWs and healthcare professionals. Through 24 in-depth interviews and ten focus group discussions, we investigated perceptions of task shifting to CHWs in the screening and referral of NCDs in Nakaseke, rural Uganda. This study employed a holistic approach targeting stakeholders involved in the implementation of task shifting programs. All interviews were audio-recorded, transcribed verbatim, and analyzed thematically guided by the framework method. RESULTS: Analysis identified elements likely to be required for successful program implementation in this context. Fundamental drivers of CHW programs included structured supervision, patients' access to care through CHWs, community involvement, remuneration and facilitation, as well as building CHW knowledge and skills through training. Additional enablers comprised specific CHW characteristics such as confidence, commitment and motivation, as well as social relations and empathy. Lastly, socioemotional aspects such as trust, virtuous behavior, recognition in the community, and the presence of mutual respect were reported to be critical to the success of task shifting programs. CONCLUSION: CHWs are perceived as a useful resource when task shifting NCD screening and referral for hypertension and diabetes from facility-based healthcare workers. Before implementation of a task shifting program, it is essential to consider the multiple layers of needs portrayed in this study. This ensures a successful program that overcomes community concerns and may serve as guidance to implement task shifting in similar settings.

SLC26A1 is a major determinant of sulfate homeostasis in humans.

Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge. Whole-exome data analysis of more than 5,000 individuals confirmed that rare, putatively damaging SCL26A1 variants were significantly associated with lower plasma sulfate at the population level. Functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, which we consider to be novel, as well as for the additional variants detected in the population study. In conclusion, combined evidence from 3 complementary approaches supports SLC26A1 activity as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis with back pain and intervertebral disc disorder, our study identifies SLC26A1 as a potential target for modulation of musculoskeletal health.

The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates.

A longevity gene called Indy (for 'I'm not dead yet'), with similarity to mammalian genes encoding sodium-dicarboxylate cotransporters, was identified in Drosophila melanogaster. Functional studies in Xenopus oocytes showed that INDY mediates the flux of dicarboxylates and citrate across the plasma membrane, but the specific transport mechanism mediated by INDY was not identified. To test whether INDY functions as an anion exchanger, we examined whether substrate efflux is stimulated by transportable substrates added to the external medium. Efflux of [14C]citrate from INDY-expressing oocytes was greatly accelerated by the addition of succinate to the external medium, indicating citrate-succinate exchange. The succinate-stimulated [14C]citrate efflux was sensitive to inhibition by DIDS (4,4'-di-isothiocyano-2,2'-disulphonic stilbene), as demonstrated previously for INDY-mediated succinate uptake. INDY-mediated efflux of [14C]citrate was also stimulated by external citrate and oxaloacetate, indicating citrate-citrate and citrate-oxaloacetate exchange. Similarly, efflux of [14C]succinate from INDY-expressing oocytes was stimulated by external citrate, alpha-oxoglutarate and fumarate, indicating succinate-citrate, succinate-alpha-oxoglutarate and succinate-fumarate exchange respectively. Conversely, when INDY-expressing Xenopus oocytes were loaded with succinate and citrate, [14C]succinate uptake was markedly stimulated, confirming succinate-succinate and succinate-citrate exchange. Exchange of internal anion for external citrate was markedly pH(o)-dependent, consistent with the concept that citrate is co-transported with a proton. Anion exchange was sodium-independent. We conclude that INDY functions as an exchanger of dicarboxylate and tricarboxylate Krebs-cycle intermediates. The effect of decreasing INDY activity, as in the long-lived Indy mutants, may be to alter energy metabolism in a manner that favours lifespan extension.