RESUMEN
BACKGROUND: Hypertension is a major risk factor of cardiovascular disease and a leading cause of morbidity and mortality globally. In Kenya, the rise of hypertension strains an already stretched health care system that has traditionally focused on the management of infectious diseases. Health care provision in this country remains fragmented, and little is known about the role of health information technology in care coordination. Furthermore, there is a dearth of literature on the experiences, challenges, and solutions for improving the management of hypertension and other noncommunicable diseases in the Kenyan private health care sector. OBJECTIVE: The aim of this study is to assess stakeholders' perspectives on the challenges associated with the management of hypertension in the Kenyan private health care sector and to derive recommendations for the design and functionality of a digital health solution for addressing the care continuity and quality challenges in the management of hypertension. METHODS: We conducted a qualitative case study. We collected data using in-depth interviews with 18 care providers and 8 business leads, and direct observations at 18 private health care institutions in Nairobi, Kenya. We analyzed the data thematically to identify the key challenges and recommendations for technology-enabled solutions to support the management of hypertension in the Kenyan private health sector. We subsequently used the generated insights to derive and describe the design and range of functions of a digital health wallet platform for enabling care quality and continuity. RESULTS: The management of hypertension in the Kenyan private health care sector is characterized by challenges such as high cost of care, limited health care literacy, lack of self-management support, ineffective referral systems, inadequate care provider training, and inadequate regulation. Care providers lack the tools needed to understand their patients' care histories and effectively coordinate efforts to deliver high-quality hypertension care. The proposed digital health platform was designed to support hypertension care coordination and continuity through clinical workflow orchestration, decision support, and patient-mediated data sharing with privacy preservation, auditability, and trust enabled by blockchain technology. CONCLUSIONS: The Kenyan private health care sector faces key challenges that require significant policy, organizational, and infrastructural changes to ensure care quality and continuity in the management of hypertension. Digital health data interoperability solutions are needed to improve hypertension care coordination in the sector. Additional studies should investigate how patients can control the sharing of their data while ensuring that care providers have a holistic view of the patient during any encounter.
Asunto(s)
Continuidad de la Atención al Paciente/normas , Sector de Atención de Salud/normas , Hipertensión/terapia , Sector Privado/normas , Calidad de la Atención de Salud/normas , Humanos , Hipertensión/epidemiología , Kenia , Investigación CualitativaRESUMEN
OBJECTIVE: Efforts to realize the potential of disease prevention in the United States have fallen behind those of peer countries, and workplace disease prevention is a major gap. This article investigates the reasons for this gap. METHODS: Literature review and expert discussions. RESULTS: Obstacles to effective use of workplace disease prevention include limited leadership and advocacy, poor alignment of financial incentives, limitations in research quality and investment, regulation that does not support evidence-based practice, and a dearth of community-employer partnerships. CONCLUSIONS: We make recommendations to address these obstacles, such as the inclusion of health metrics in corporate reporting, making the workplace a central component of the strategy to combat the effect of noncommunicable diseases, and linking prevention directly benefit businesses' bottom lines.
Asunto(s)
Enfermedad Crónica/prevención & control , Promoción de la Salud , Lugar de Trabajo , Conductas Relacionadas con la Salud , Promoción de la Salud/economía , Promoción de la Salud/legislación & jurisprudencia , Humanos , Liderazgo , Asociación entre el Sector Público-Privado , Estados UnidosRESUMEN
Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. This reaction supports S-adenosylmethionine biosynthesis, which is required for hundreds of methylation reactions in humans. Herein we report that BHMT is activated by potassium ions with an apparent K(M) for K⺠of about 100 µM. The presence of potassium ions lowers the apparent K(M) of the enzyme for homocysteine, but it does not affect the apparent K(M) for betaine or the apparent k(cat) for either substrate. We employed molecular dynamics (MD) simulations to theoretically predict and protein crystallography to experimentally localize the binding site(s) for potassium ion(s). Simulations predicted that K⺠ion would interact with residues Asp26 and/or Glu159. Our crystal structure of BHMT bound to homocysteine confirms these sites of interaction and reveals further contacts between K⺠ion and BHMT residues Gly27, Gln72, Gln247, and Gly298. The potassium binding residues in BHMT partially overlap with the previously identified DGG (Asp26-Gly27-Gly28) fingerprint in the Pfam 02574 group of methyltransferases. Subsequent biochemical characterization of several site-specific BHMT mutants confirmed the results obtained by the MD simulations and crystallographic data. Together, the data herein indicate that the role of potassium ions in BHMT is structural and that potassium ion facilitates the specific binding of homocysteine to the active site of the enzyme.
Asunto(s)
Betaína-Homocisteína S-Metiltransferasa/metabolismo , Homocisteína/metabolismo , Modelos Moleculares , Potasio/metabolismo , Betaína/química , Betaína/metabolismo , Betaína-Homocisteína S-Metiltransferasa/química , Betaína-Homocisteína S-Metiltransferasa/genética , Sitios de Unión , Dominio Catalítico , Cristalografía por Rayos X , Bases de Datos de Proteínas , Activación Enzimática , Homocisteína/química , Humanos , Cinética , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Potasio/química , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Especificidad por SustratoRESUMEN
Methylation of homocysteine (Hcy) by betaine-Hcy S-methyltransferase (BHMT) produces methionine, which is required for S-adenosylmethionine (SAM) synthesis. We have recently shown that short-term dietary intake of S-(Δ-carboxybutyl)-dl-Hcy (D,L-CBHcy), a potent and specific inhibitor of BHMT, significantly decreases liver BHMT activity and SAM concentrations but does not have an adverse affect on liver histopathology, plasma markers of liver damage, or DNA methylation in rats. The present study was designed to investigate the hypothesis that BHMT is required to maintain normal liver and plasma amino acid and glutathione profiles, and liver SAM and lipid accumulation. Rats were fed an adequate (4.5 g/kg methionine and 3.7 g/kg cystine), cysteine-devoid (4.5 g/kg methionine and 0 g/kg cystine), or methionine-deficient (1.5 g/kg methionine and 3.7 g/kg cystine) diet either with or without L-CBHcy for 3 or 14 days. All rats fed L-CBHcy had increased total plasma Hcy (2- to 5-fold) and reduced liver BHMT activity (>90%) and SAM concentrations (>40%). S-(Δ-carboxybutyl)-l-Hcy treatment slightly reduced liver glutathione levels in rats fed the adequate or cysteine-devoid diet for 14 days. Rats fed the methionine-deficient diet with L-CBHcy developed fatty liver. Liver cystathionine ß-synthase activity was reduced in all L-CBHcy-treated animals, and the effect was exacerbated as time on the L-CBHcy diet increased. Our data indicate that BHMT activity is required to maintain adequate levels of liver SAM and low levels of total plasma Hcy and might be critical for liver glutathione and triglyceride homeostasis under some dietary conditions.