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1.
Int J Chron Obstruct Pulmon Dis ; 18: 2769-2783, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38046984

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda. Methods: This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis. Results: Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs. Conclusion: CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.


Assuntos
Agentes Comunitários de Saúde , Doença Pulmonar Obstrutiva Crônica , Humanos , Uganda/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Pesquisa Qualitativa , Encaminhamento e Consulta
2.
JMIR Res Protoc ; 12: e46614, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032702

RESUMO

BACKGROUND: Uncontrolled hypertension is a leading risk factor for cardiovascular diseases. In Uganda, such diseases account for approximately 10% of all deaths, with 1 in 5 adults having hypertension (>90% of the hypertensive cases are uncontrolled). Although basic health care in the country is available free of cost at government facilities, regularly accessing medication to control hypertension is difficult because supply chain challenges impede availability. Clients therefore frequently suspend treatment or buy medication individually at private facilities or pharmacies (incurring significant costs). In recent years, mobile health (mHealth) interventions have shown increasing potential in addressing health system challenges in sub-Saharan Africa, but the acceptability, feasibility, and uptake conditions of mobile money approaches to chronic disease management remain understudied. OBJECTIVE: This study aims to design and pilot-test a mobile money-based intervention to increase the availability of antihypertensive medication and lower clients' out-of-pocket payments. We will build on existing local approaches and assess the acceptability, feasibility, and uptake of the designed intervention. Furthermore, rather than entering the study setting with a ready-made intervention, this research will place emphasis on gathering applied ethnographic insights early, which can then inform the parameters of the intervention prototype and concurrent trial. METHODS: We will conduct a mixed methods study following a human-centered design approach. We will begin by conducting extensive qualitative research with a range of stakeholders (clients; health care providers; religious, cultural, and community leaders; academics; and policy makers at district and national levels) on their perceptions of hypertension management, money-saving systems, and mobile money in the context of health care. Our results will inform the design, iterative adaptation, and implementation of an mHealth-facilitated pooled financing intervention prototype. At study conclusion, the finalized prototype will be evaluated quantitatively via a randomized controlled trial. RESULTS: As of August 2023, qualitative data collection, which started in November 2022, is ongoing, with data analysis of the first qualitative interviews underway to inform platform and implementation design. Recruitment for the quantitative part of this study began in August 2023. CONCLUSIONS: Our results aim to inform the ongoing discourse on novel and sustainable pathways to facilitate access to medication for the management of hypertension in resource-constrained settings. TRIAL REGISTRATION: German registry of clinical trials DRKS00030922; https://drks.de/search/en/trial/DRKS00030922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46614.

3.
Clin J Am Soc Nephrol ; 18(12): 1637-1644, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37342976

RESUMO

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.


Assuntos
Hiperoxalúria , Cálculos Renais , Insuficiência Renal , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/terapia , Oxalatos/urina , Cálculos Renais/etiologia , Oxalato de Cálcio/urina , Insuficiência Renal/complicações
4.
BMC Public Health ; 23(1): 881, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173687

RESUMO

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.


Assuntos
Diabetes Mellitus , Hipertensão , Feminino , Humanos , Agentes Comunitários de Saúde/psicologia , Uganda , Pesquisa Qualitativa , Hipertensão/diagnóstico , Hipertensão/terapia , Acessibilidade aos Serviços de Saúde , Encaminhamento e Consulta , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia
5.
Kidney Int ; 104(1): 90-107, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37121432

RESUMO

The polyamines spermidine and spermine and their common precursor molecule putrescine are involved in tissue injury and repair. Here, we test the hypothesis that impaired polyamine homeostasis contributes to various kidney pathologies in mice during experimental models of ischemia-reperfusion, transplantation, rhabdomyolysis, cyclosporine treatment, arterial hypertension, diabetes, unilateral ureteral obstruction, high oxalate feeding, and adenine-induced injuries. We found a remarkably similar pattern in most kidney pathologies with reduced expression of enzymes involved in polyamine synthesis together with increased expression of polyamine degrading enzymes. Transcript levels of amine oxidase copper-containing 1 (Aoc1), an enzyme which catalyzes the breakdown of putrescine, were barely detectable by in situ mRNA hybridization in healthy kidneys. Aoc1 was highly expressed upon various experimental kidney injuries resulting in a significant reduction of kidney putrescine content. Kidney levels of spermine were also significantly reduced, whereas spermidine was increased in response to ischemia-reperfusion injury. Increased Aoc1 expression in injured kidneys was mainly accounted for by an Aoc1 isoform that harbors 22 additional amino acids at its N-terminus and shows increased secretion. Mice with germline deletion of Aoc1 and injured kidneys showed no decrease of kidney putrescine content; although they displayed no overt phenotype, they had fewer tubular casts upon ischemia-reperfusion injury. Hyperosmotic stress stimulated AOC1 expression at the transcriptional and post-transcription levels in metanephric explants and kidney cell lines. AOC1 expression was also significantly enhanced after kidney transplantation in humans. These data demonstrate that the kidneys respond to various forms of injury with down-regulation of polyamine synthesis and activation of the polyamine breakdown pathway. Thus, an imbalance in kidney polyamines may contribute to various etiologies of kidney injury.


Assuntos
Amina Oxidase (contendo Cobre) , Traumatismo por Reperfusão , Humanos , Camundongos , Animais , Poliaminas/metabolismo , Espermidina/metabolismo , Putrescina/metabolismo , Espermina/metabolismo , Espermina/farmacologia , Acetiltransferases/genética , Acetiltransferases/metabolismo , Rim/patologia , Amina Oxidase (contendo Cobre)/metabolismo , Traumatismo por Reperfusão/patologia , Expressão Gênica
6.
Microbiol Spectr ; : e0213921, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36790203

RESUMO

Sub-Saharan Africa has increased morbidity and mortality related to chronic obstructive pulmonary disease (COPD). COPD among people living with HIV (PLWH) has not been well studied in this region, where HIV/AIDS is endemic. Increasing evidence suggests that respiratory microbial composition plays a role in COPD severity. Therefore, we aimed to investigate microbiome patterns and associations among PLWH with COPD in Sub-Saharan Africa. We conducted a cross-sectional study of 200 adults stratified by HIV and COPD in rural Uganda. Induced sputum samples were collected as an easy-to-obtain proxy for the lower respiratory tract microbiota. We performed 16S rRNA gene sequencing and used PICRUSt2 (version 2.2.3) to infer the functional profiles of the microbial community. We used a statistical tool to detect changes in specific taxa that searches and adjusts for confounding factors such as antiretroviral therapy (ART), age, sex, and other participant characteristics. We could cluster the microbial community into three community types whose distribution was shown to be significantly impacted by HIV. Some genera, e.g., Veillonella, Actinomyces, Atopobium, and Filifactor, were significantly enriched in HIV-infected individuals, while the COPD status was significantly associated with Gammaproteobacteria and Selenomonas abundance. Furthermore, reduced bacterial richness and significant enrichment in Campylobacter were associated with HIV-COPD comorbidity. Functional prediction using PICRUSt2 revealed a significant depletion in glutamate degradation capacity pathways in HIV-positive patients. A comparison of our findings with an HIV cohort from the United Kingdom revealed significant differences in the sputum microbiome composition, irrespective of viral suppression. IMPORTANCE Even with ART available, HIV-infected individuals are at high risk of suffering comorbidities, as shown by the high prevalence of noninfectious lung diseases in the HIV population. Recent studies have suggested a role for the respiratory microbiota in driving chronic lung inflammation. The respiratory microbiota was significantly altered among PLWH, with disease persisting up to 3 years post-ART initiation and HIV suppression. The community structure and diversity of the sputum microbiota in COPD are associated with disease severity and clinical outcomes, both in stable COPD and during exacerbations. Therefore, a better understanding of the sputum microbiome among PLWH could improve COPD prognostic and risk stratification strategies. In this study, we observed that in a virologically suppressed HIV cohort in rural Uganda, we could show differences in sputum microbiota stratified by HIV and COPD, reduced bacterial richness, and significant enrichment in Campylobacter associated with HIV-COPD comorbidity.

7.
J Clin Invest ; 133(3)2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36719378

RESUMO

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.


Assuntos
Proteínas de Transporte de Ânions , Sulfatos , Animais , Camundongos , Humanos , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Transporte de Íons , Sulfatos/metabolismo , Homeostase , Camundongos Knockout , Antiporters/genética
8.
Nat Rev Nephrol ; 19(2): 123-138, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36329260

RESUMO

Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions.


Assuntos
Hiperoxalúria , Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Oxalatos/metabolismo , Oxalatos/farmacologia , Oxalatos/uso terapêutico , Diálise Renal , Rim/metabolismo , Hiperoxalúria/terapia , Hiperoxalúria/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal/complicações , Homeostase
10.
Trials ; 23(1): 440, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610712

RESUMO

BACKGROUND: Over 80% of the morbidity and mortality related to non-communicable diseases (NCDs) occurs in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, particularly in sub-Saharan African settings. In Uganda, and the majority of LMICs, management of uncontrolled hypertension remains limited in constrained health systems. Intervening at the primary care level, using CHWs to improve medical treatment outcomes has not been well studied. We aim to determine the effectiveness of a CHW-led intervention in blood pressure control among confirmed hypertensive patients and patient-related factors associated with uncontrolled hypertension. METHODS: We will conduct a stepped-wedge cluster randomized controlled trial study of 869 adult patients with hypertension attending two NCD clinics to test the effectiveness, acceptability, and fidelity of a CHW-led intervention. The multi-component intervention will be centered on monthly household visits by trained CHWs for a period of 1 year, consisting of the following: (1) blood pressure and sugar monitoring, (2) BMI monitoring, (3) cardiovascular disease risk assessment, (4) using checklists to guide monitoring and referral to clinics, and (5) healthy lifestyle counseling and education. During home visits, CHWs will remind patients of follow-up visits. We will measure blood pressure at baseline and 3-monthly for the entire cohort. We will conduct individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community. CONCLUSION: The results of this study will inform community delivered HTN management across a range of LMIC settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05068505 . Registered on October 6, 2021.


Assuntos
Agentes Comunitários de Saúde , Hipertensão , Adulto , Pressão Sanguínea , Serviços de Saúde Comunitária , Humanos , Hipertensão/diagnóstico , Hipertensão/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Uganda
12.
Artigo em Inglês | MEDLINE | ID: mdl-35633593

RESUMO

Cardiovascular disease is the leading cause of mortality in patients with renal failure. Red blood cells (RBCs) are potential reservoirs for epoxy fatty acids (oxylipins) that regulate cardiovascular function. Hemoglobin exhibits pseudo-lipoxygenase activity in vitro. We previously assessed the impact of single hemodialysis (HD) treatment on RBC epoxy fatty acids status in circulating arterial blood and found that eicosanoids in oxygenated RBCs could be particularly vulnerable in chronic kidney disease and hemodialysis. The purpose of the present study was to evaluate the differences of RBC epoxy fatty acids profiles in arterial and venous blood in vivo (AV differences) from patients treated by HD treatment. We collected arterial and venous blood samples in upper limbs from 12 end-stage renal disease (ESRD) patients (age 72±12 years) before and after HD treatment. We measured oxylipins derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in RBCs by LC-MS/MS tandem mass spectrometry. Our data demonstrate arteriovenous differences in LOX pathway metabolites in RBCs after dialysis, including numerous hydroxyeicosatetraenoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and hydroxyeicosapentaenoic acids (HEPEs). We detected more pronounced changes in free metabolites in RBCs after HD, as compared with the total RBC compartment. Hemodialysis treatment did not affect the majority of CYP and CYP ω/(ω-1)-hydroxylase products in RBCs. Our data indicate that erythro-metabolites of the LOX pathway are influenced by renal-replacement therapies, which could have deleterious effects in the circulation.


Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos , Idoso , Idoso de 80 Anos ou mais , Biotransformação , Cromatografia Líquida , Sistema Enzimático do Citocromo P-450/metabolismo , Eritrócitos/metabolismo , Ácidos Graxos/metabolismo , Humanos , Lipoxigenase/metabolismo , Pessoa de Meia-Idade , Oxilipinas , Diálise Renal , Espectrometria de Massas em Tandem
13.
Metabolites ; 12(3)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35323712

RESUMO

Long-chain fatty acids (LCFAs) serve as energy sources, components of cell membranes, and precursors for signaling molecules. Uremia alters LCFA metabolism so that the risk of cardiovascular events in chronic kidney disease (CKD) is increased. End-stage renal disease (ESRD) patients undergoing dialysis are particularly affected and their hemodialysis (HD) treatment could influence blood LCFA bioaccumulation and transformation. We investigated blood LCFA in HD patients and studied LCFA profiles in vivo by analyzing arterio-venous (A-V) LFCA differences in upper limbs. We collected arterial and venous blood samples from 12 ESRD patients, before and after HD, and analyzed total LCFA levels in red blood cells (RBCs) and plasma by LC-MS/MS tandem mass spectrometry. We observed that differences in arterial and venous LFCA contents within RBCs (RBC LCFA A-V differences) were affected by HD treatment. Numerous saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) n-6 showed negative A-V differences, accumulated during peripheral tissue perfusion of the upper limbs, in RBCs before HD. HD reduced these differences. The omega-3 quotient in the erythrocyte membranes was not affected by HD in either arterial or venous blood. Our data demonstrate that A-V differences in fatty acids status of LCFA are present and active in mature erythrocytes and their bioaccumulation is sensitive to single HD treatment.

14.
Metabolites ; 12(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35050156

RESUMO

Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.

15.
J Clin Endocrinol Metab ; 107(1): e281-e292, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34390334

RESUMO

CONTEXT: Abnormalities in calcium metabolism are common in chronic kidney disease (CKD). Diminished urinary calcium excretion may promote vascular calcification and increased urinary calcium excretion may lead to nephrolithiasis and nephrocalcinosis, conditions associated with CKD. OBJECTIVE: To study predictors of urinary calcium excretion and its association with adverse clinical outcomes in CKD. DESIGN, SETTING AND PATIENTS: This study assessed 3768 nondialysis participants in the Chronic Renal Insufficiency Cohort study from April 2003 to September 2008. Participants were followed up to October 2018. EXPOSURE: Clinically plausible predictors of urinary calcium excretion and 24-h urinary calcium excretion at baseline. MAIN OUTCOME MEASURES: Urinary calcium excretion; incident end stage kidney disease (ESKD), CKD progression [50% estimated glomerular filtration rate (eGFR) decline or incident ESKD], all-cause mortality, and atherosclerotic cardiovascular disease events. RESULTS: eGFR was positive correlated with 24-h urinary calcium excretion. The variables most strongly associated with 24-h urinary calcium excretion in males and females were 24-h urinary sodium (ß = 0.19 and 0.28, respectively), serum parathyroid hormone (ß = -0.22 and -0.20, respectively), loop diuretics (ß = 0.36 and 0.26, respectively), thiazide diuretics (ß = -0.49 and -0.53, respectively), and self-identified black race (ß = -0.23 and -0.27, respectively). Lower urinary calcium excretion was associated with greater risks of adverse outcomes, but these associations were greatly attenuated or nullified after adjustment for baseline eGFR. CONCLUSION: Urinary calcium excretion is markedly lower in individuals with CKD compared to the general population. Determinants of urinary calcium excretion differed between sexes and levels of CKD. Associations between urinary calcium excretion and adverse clinical events were substantially confounded by eGFR.


Assuntos
Aterosclerose/epidemiologia , Cálcio/urina , Falência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Idoso , Aterosclerose/etiologia , Cálcio/metabolismo , Fatores de Confusão Epidemiológicos , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Incidência , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Eliminação Renal , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Fatores Sexuais , Análise de Sobrevida
16.
Gastroenterology ; 162(3): 844-858, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34822802

RESUMO

BACKGROUND & AIMS: The protozoa Giardia duodenalis is a major cause of gastrointestinal illness worldwide, but underlying pathophysiological mechanisms remain obscure, partly due to the absence of adequate cellular models. We aimed at overcoming these limitations and recapitulating the authentic series of pathogenic events in the primary human duodenal tissue by using the human organoid system. METHODS: We established a compartmentalized cellular transwell system with electrophysiological and barrier properties akin to duodenal mucosa and dissected the events leading to G. duodenalis-induced barrier breakdown by functional analysis of transcriptional, electrophysiological, and tight junction components. RESULTS: Organoid-derived cell layers of different donors showed a time- and parasite load-dependent leak flux indicated by collapse of the epithelial barrier upon G. duodenalis infection. Gene set enrichment analysis suggested major expression changes, including gene sets contributing to ion transport and tight junction structure. Solute carrier family 12 member 2 and cystic fibrosis transmembrane conductance regulator-dependent chloride secretion was reduced early after infection, while changes in the tight junction composition, localization, and structural organization occurred later as revealed by immunofluorescence analysis and freeze fracture electron microscopy. Functionally, barrier loss was linked to the adenosine 3',5'-cyclic monophosphate (cAMP)/protein kinase A-cAMP response element-binding protein signaling pathway. CONCLUSIONS: Data suggest a previously unknown sequence of events culminating in intestinal barrier dysfunction upon G. duodenalis infection during which alterations of cellular ion transport were followed by breakdown of the tight junctional complex and loss of epithelial integrity, events involving a cAMP/protein kinase A-cAMP response element-binding protein mechanism. These findings and the newly established organoid-derived model to study G. duodenalis infection may help to explore new options for intervening with disease and infection, in particular relevant for chronic cases of giardiasis.


Assuntos
Giardíase/fisiopatologia , Mucosa Intestinal/fisiopatologia , Transporte de Íons , Transdução de Sinais , Junções Íntimas/fisiologia , Apoptose , Células CACO-2 , Cloretos/metabolismo , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Duodeno , Impedância Elétrica , Giardia lamblia , Giardíase/genética , Giardíase/imunologia , Humanos , Interleucina-1/genética , Transporte de Íons/genética , NF-kappa B/genética , Organoides , Carga Parasitária , Membro 2 da Família 12 de Carreador de Soluto/genética , Junções Íntimas/genética , Junções Íntimas/patologia , Junções Íntimas/ultraestrutura , Transcriptoma , Fator de Necrose Tumoral alfa/genética
17.
NEJM Evid ; 1(7): EVIDoa2100053, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38319254

RESUMO

Reloxaliase in Enteric HyperoxaluriaPatients with enteric hyperoxaluria received reloxaliase or placebo with food for 4 weeks. Urinary oxalate excretion decreased from 83.2 to 67.4 mg/24 hr during weeks 1 to 4 with reloxaliase compared with 84.2 to 78.1 mg/24 hr with placebo (P=0.004). Adverse events occurred for 69% of reloxaliase-treated patients versus 53% of those receiving placebo.

18.
BMC Public Health ; 21(1): 2036, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743687

RESUMO

BACKGROUND: Non-communicable diseases (NCDs) are an increasing global concern, with morbidity and mortality largely occurring in low- and middle-income settings. We established the prospective Rural Uganda Non-Communicable Disease (RUNCD) cohort to longitudinally characterize the NCD prevalence, progression, and complications in rural Africa. METHODS: We conducted a population-based census for NCD research. We systematically enrolled adults in each household among three sub-counties of the larger Nakaseke Health district and collected baseline demographic, health status, and self-reported chronic disease information. We present our data on self-reported chronic disease, as stratified by age, sex, educational attainment, and sub-county. RESULTS: A total of 16,694 adults were surveyed with 10,563 (63%) respondents enrolled in the self-reported study. Average age was 37.8 years (SD = 16.5) and 45% (7481) were male. Among self-reported diseases, hypertension (HTN) was most prevalent (6.3%). 1.1% of participants reported a diagnosis of diabetes, 1.1% asthma, 0.7% COPD, and 0.4% kidney disease. 2.4% of the population described more than one NCD. Self-reported HTN was significantly higher in the peri-urban subcounty than in the other two rural sub-counties (p < 0.001); diagnoses for all other diseases did not differ significantly between sub-counties. Odds for self-reported HTN increased significantly with age (OR = 1.87 per 10 years of age, 95% CI 1.78-1.96). Male sex was associated with lower odds of reporting asthma (OR = 0.53, 95% CI 0.34-0.82) or HTN (OR = 0.31, 95% CI 0.26-0.40). CONCLUSIONS: The RUNCD will establish one of the largest NCD patient cohorts in rural Africa. First analysis highlights the feasibility of systematically enrolling large numbers of adults living in a rural Ugandan district. In addition, our study demonstrates low levels of self-reported NCDs compared to the nation-wide established levels, emphasizing the need to better educate, characterize, and care for the majority of rural communities.


Assuntos
Doenças não Transmissíveis , Adulto , Criança , Estudos Transversais , Humanos , Masculino , Doenças não Transmissíveis/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , População Rural , Autorrelato , Uganda/epidemiologia
20.
BMC Public Health ; 21(1): 1343, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233648

RESUMO

BACKGROUND: The prevalence of hypertension is increasing among people living with HIV/AIDS (PLWHA) in low- and middle-income countries (LMICs). However, knowledge of the complications and management of hypertension among PLWHA in Uganda remains low. We explored the acceptability of implementing hypertension (HTN) specific health education by community health workers (CHWs) among PLWHA in rural Uganda. METHODS: We conducted a qualitative study consisting of 22 in-depth interviews (14 PLWHA/HTN and 8 CHWs), 3 focus group discussions (FGDs), 2 with PLWHA/HTN and 1 with CHWs from Nakaseke district, Uganda. Participants were interviewed after a single session interaction with the CHW. Data were transcribed from luganda (local language) into English and analyzed using thematic analysis. We used Sekhon's model of acceptability of health Interventions to explore participants' perceptions. RESULTS: Participants believed CHWs utilized easy-to-understand, colloquial, non-technical language during education delivery, had a pre-existing rapport with the CHWs that aided faster communication, and had more time to explain illness than medical doctors had. Participants found the educational material (PocketDoktor™) to be simple and easy to understand, and perceived that the education would lead to improved health outcomes. Participants stated their health was a priority and sought further disease-specific information. We also found that CHWs were highly motivated to carry out the patient-centered education. While delivering the education, CHWs experienced difficulties in keeping up with the technical details regarding hypertension in the PocketDoktor™, financial stress and patient questions beyond their self-perceived skill level and experience. PLWHA/HTN had challenges accessing the health facility where the intervention was delivered and preferred a household setting. CONCLUSIONS: Hypertension patient-centered education delivered by CHWs using the PocketDoktor™ was acceptable to PLWHA and hypertension in Nakaseke area in rural, Uganda. There is need for further studies to determine the cost implications of delivering this intervention among PLWHA across LMIC settings.


Assuntos
Infecções por HIV , Hipertensão , Agentes Comunitários de Saúde , Infecções por HIV/terapia , Educação em Saúde , Humanos , Hipertensão/terapia , Assistência Centrada no Paciente , Pesquisa Qualitativa , Uganda
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