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BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.
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Diabetes Mellitus Tipo 2 , Metformina , Doenças Periodontais , Animais , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Glicemia , Doenças Periodontais/tratamento farmacológico , Gerenciamento ClínicoRESUMO
OBJECTIVES: To assess psychometric properties of two scales developed to measure the quality of person-centered care during pregnancy and childbirth in the United States-the Person-Centered Prenatal Care (PCPC-US) and Person-Centered Maternity Care (PCMC-US) scales-in a low-income predominantly Latinx population in California. METHODS: Data were collected from July 2020 to June 2023 from surveys of low-income pregnant and birthing people in Fresno, California, participating in the "Engaging Mothers and Babies; Reimagining Antenatal Care for Everyone" (EMBRACE) trial. Research staff administered the 26-item PCPC-US scale at 30-34 weeks' gestation (n = 315) and the 35-item PCMC-US scale at 10-14 weeks after birth (n = 286), using the language preferred by the participant (English or Spanish). We assessed construct, criterion, and known group validity and internal consistency of the scales. RESULTS: 78% of respondents identified as Latinx. Factor analysis identified one dominant factor for each scale that accounted for over 60% of the cumulative variance, with most items loading at > 0.3. The items also loaded adequately on sub-scales for "dignity and respect," "communication and autonomy," and "responsive and supportive care." Cronbach's alpha for the full scales were > 0.9 and between 0.70 and 0.87 for the sub-scales. Summative scores range from 0 to 100, with higher scores indicating higher person-centered care. Correlations with scores on scales measuring prenatal care quality and birth experience provided evidence for criterion validity, while associations with known predictors provided evidence for known-group validity. CONCLUSIONS: The PCPC-US and PCMC-US scales, which were developed using a community-engaged process and found to have good psychometric properties in a largely high-income sample of Black women, were shown to also have good psychometric properties in a sample of low-income primarily Latinx women. Both scales provide valid and reliable tools to measure person-centered care experiences among minoritized communities to support efforts to reduce existing birth inequities.
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Serviços de Saúde Materna , Obstetrícia , Assistência Centrada no Paciente , Feminino , Humanos , Gravidez , California , Hispânico ou Latino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Electronic health record (EHR) prediction models may be easier to use in busy clinical settings since EHR data can be auto-populated into models. This study assessed whether adding functional status and/or Medicare claims data (which are often not available in EHRs) improves the accuracy of a previously developed Veterans Affairs (VA) EHR-based mortality index. METHODS: This was a retrospective cohort study of veterans aged 75 years and older enrolled in VA primary care clinics followed from January 2014 to April 2020 (n = 62,014). We randomly split participants into development (n = 49,612) and validation (n = 12,402) cohorts. The primary outcome was all-cause mortality. We performed logistic regression with backward stepwise selection to develop a 100-predictor base model using 854 EHR candidate variables, including demographics, laboratory values, medications, healthcare utilization, diagnosis codes, and vitals. We incorporated functional measures in a base + function model by adding activities of daily living (range 0-5) and instrumental activities of daily living (range 0-7) scores. Medicare data, including healthcare utilization (e.g., emergency department visits, hospitalizations) and diagnosis codes, were incorporated in a base + Medicare model. A base + function + Medicare model included all data elements. We assessed model performance with the c-statistic, reclassification metrics, fraction of new information provided, and calibration plots. RESULTS: In the overall cohort, mean age was 82.6 years and 98.6% were male. At the end of follow-up, 30,263 participants (48.8%) had died. The base model c-statistic was 0.809 (95% CI 0.805-0.812) in the development cohort and 0.804 (95% CI 0.796-0.812) in the validation cohort. Validation cohort c-statistics for the base + function, base + Medicare, and base + function + Medicare models were 0.809 (95% CI 0.801-0.816), 0.811 (95% CI 0.803-0.818), and 0.814 (95% CI 0.807-0.822), respectively. Adding functional status and Medicare data resulted in similarly small improvements among other model performance measures. All models showed excellent calibration. CONCLUSIONS: Incorporation of functional status and Medicare data into a VA EHR-based mortality index led to small but likely clinically insignificant improvements in model performance.
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Medicare , Veteranos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Estado Funcional , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia , United States Department of Veterans AffairsRESUMO
BACKGROUND: Pharmacy dispensing data are frequently used to identify prevalent medication use as a predictor or covariate in observational research studies. Although several methods have been proposed for using pharmacy dispensing data to identify prevalent medication use, little is known about their comparative performance. OBJECTIVES: The authors sought to compare the performance of different methods for identifying prevalent outpatient medication use. RESEARCH DESIGN: Outpatient pharmacy fill data were compared with medication reconciliation notes denoting prevalent outpatient medication use at the time of hospital admission for a random sample of 207 patients drawn from a national cohort of patients admitted to Veterans Affairs hospitals. Using reconciliation notes as the criterion standard, we determined the test characteristics of 12 pharmacy database algorithms for determining prevalent use of 11 classes of cardiovascular and diabetes medications. RESULTS: The best-performing algorithms included a 180-day fixed look-back period approach (sensitivity, 93%; specificity, 97%; and positive predictive value, 89%) and a medication-on-hand approach with a grace period of 60 days (sensitivity, 91%; specificity, 97%; and positive predictive value, 91%). Algorithms that have been commonly used in previous studies, such as defining prevalent medications to include any medications filled in the prior year or only medications filled in the prior 30 days, performed less well. Algorithm performance was less accurate among patients recently receiving hospital or nursing facility care. CONCLUSION: Pharmacy database algorithms that balance recentness of medication fills with grace periods performed better than more simplistic approaches and should be considered for future studies which examine prevalent chronic medication use.
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Bases de Dados Factuais/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Reconciliação de Medicamentos/métodos , Pacientes Ambulatoriais/estatística & dados numéricos , Farmácias/estatística & dados numéricos , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estados UnidosRESUMO
This study assesses whether colorectal cancer screening varied by predicted life expectancy in a national sample of Veterans Affairs patients aged 76 to 85 years.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Expectativa de Vida , Humanos , Fatores Etários , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Estados Unidos/epidemiologia , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: This is the first review to analyze literature identifying risk factors for a multidrug-resistant urinary tract infection (MDR UTI). Risk factors for other infections involving multidrug-resistant organisms have been evaluated in other reviews, but they do not assess urinary tract infections. The purpose of this study is to collect currently published data to determine the most commonly and consistently identified risk factors for UTIs. MATERIAL AND METHODS: For this study, 3 independent researchers searched PubMed, Embase, and Cochrane database from 1966 to February 2016 for articles identifying risk factors for MDR UTI. RESULTS: A total of 25 studies including 31,284 patients with positive cultures provide evidence for 12 possible risk factors for MDR UTI . The most commonly identified risk factor was previous antibiotic usage as evidenced in 16 of the 20 studies that evaluated this possible risk factor. The time range utilized to define previous antibiotic usage ranged from 2â¯days to 365â¯days. Other risk factors with the strongest supporting data were urinary catheterization, previous hospitalization, and nursing home residence. CONCLUSION: We identified 12 different possible risk factors for a MDR UTI, however several risk factors have minimal or conflicting evidence. The definitions of the risk factors varied widely among the studies, and should be standardized for future studies.
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Anti-Hipertensivos , Alta do Paciente , Idoso , Hospitalização , Hospitais , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: There has been concern over rising use of prescription opioids in young and middle-aged adults. Much less is known about opioid prescribing in older adults, for whom clinical recommendations and the balance of risks and benefits differ from younger adults. We evaluated changes in use of opioids and other analgesics in a national sample of clinic visits made by older adults between 1999 and 2010. DESIGN, SETTING, AND SUBJECTS: Observational study of adults aged 65 and older from the 1999-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, serial cross-sectional surveys of outpatient visits in the United States. METHODS: Medication use was assessed at each study visit and included medications in use prior to the visit and medications newly prescribed at the visit. Results were adjusted for survey weights and design factors to provide nationally representative estimates. RESULTS: Mean age was 75 ± 7 years, and 45% of visits occurred in primary care settings. Between 1999-2000 and 2009-2010, the percent of clinic visits at which an opioid was used rose from 4.1% to 9.0% (P < 0.001). Although use of all major opioid classes increased, the largest contributor to increased use was hydrocodone-containing combination opioids, which rose from 1.1% to 3.5% of visits over the study period (P < 0.001). Growth in opioid use was observed across a wide range of patient and clinic characteristics, including in visits for musculoskeletal problems (10.7% of visits in 1999-2000 to 17.0% in 2009-2010, P < 0.001) and in visits for other reasons (2.8% to 7.3%, P < 0.001). CONCLUSIONS: Opioid use by older adults visiting clinics more than doubled between 1999 and 2010, and occurred across a wide range of patient characteristics and clinic settings.
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Analgésicos Opioides/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Analgésicos/uso terapêutico , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Masculino , Estados UnidosRESUMO
OBJECTIVE: Synovial fluid (SF)-derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population. METHODS: In this study, we used single-cell RNA sequencing paired with single-cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition. RESULTS: The TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood. CONCLUSION: Our results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire.
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Despite its importance for clinical care and outcomes among older adults, functional status-the ability to perform basic activities of daily living (ADLs) and instrumental ADLs (IADLs)-is seldom routinely measured in primary care settings. The objective of this study was to pilot test a person-centered, interprofessional intervention to improve identification and management of functional impairment among older adults in Veterans Affairs (VA) primary care practices. The four-component intervention included (1) an interprofessional educational session; (2) routine, standardized functional status measurement among patients aged ≥75; (3) annual screening by nurses using a standardized instrument and follow-up assessment by primary care providers; and (4) electronic tools and templates to facilitate increased identification and improved management of functional impairment. Surveys, semi-structured interviews, and electronic health record data were used to measure implementation outcomes (appropriateness, acceptability and satisfaction, feasibility, fidelity, adoption/reach, sustainability). We analyzed qualitative interviews using rapid qualitative analysis. During the study period, all 959 eligible patients were screened (100% reach), of whom 7.3% (n = 58) reported difficulty or needing help with ≥1 ADL and 11.8% (n = 113) reported difficulty or needing help with ≥1 IADL. In a chart review among a subset of 50 patients with functional impairment, 78% percent of clinician notes for the visit when screening was completed had content related to function, and 48% of patients had referrals ordered to address impairments (e.g., physical therapy) within 1 week. Clinicians highly rated the quality of the educational session and reported increased ability to measure and communicate about function. Clinicians and patients reported that the intervention was appropriate, acceptable, and feasible to complete, even during the COVID pandemic. These findings suggest that this intervention is a promising approach to improve identification and management of functional impairment for older patients in primary care. Broader implementation and evaluation of this intervention is currently underway.
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Atividades Cotidianas , Atenção Primária à Saúde , Humanos , Idoso , Atenção Primária à Saúde/métodos , Projetos Piloto , Feminino , Masculino , Idoso de 80 Anos ou mais , Estado Funcional , Avaliação Geriátrica/métodos , COVID-19/epidemiologia , Estados UnidosRESUMO
Importance: Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents. Objective: To assess the association between antihypertensive medication initiation and risk of fracture. Design, Setting, and Participants: This was a retrospective cohort study using target trial emulation for data derived from 29â¯648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023. Exposure: Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy. Main Outcome and Measures: The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching. Results: Data from 29â¯648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28â¯952 [97.7%] male). In the propensity score-matched cohort of 64â¯710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]). Conclusions and Relevance: Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.
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Anti-Hipertensivos , Fraturas Ósseas , Casas de Saúde , United States Department of Veterans Affairs , Humanos , Masculino , Feminino , Anti-Hipertensivos/uso terapêutico , Estudos Retrospectivos , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Idoso , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Hipertensão/epidemiologia , Fatores de Risco , Instituição de Longa Permanência para Idosos/estatística & dados numéricosRESUMO
OBJECTIVE: Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home. METHODS: 41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders. RESULTS: We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain. CONCLUSIONS: We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.
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Hipertensão , Casas de Saúde , Humanos , Idoso , Masculino , Feminino , Hipertensão/epidemiologia , Idoso de 80 Anos ou mais , Estados Unidos , Fatores Socioeconômicos , Características da Vizinhança , Características de Residência/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Fatores de RiscoRESUMO
OBJECTIVES: Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 24,870 Department of Veterans Affairs (VA) nursing home residents aged ≥65 years with long-term stays (≥180 days) from 2006 to 2019. METHODS: We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission. RESULTS: More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years). CONCLUSIONS AND IMPLICATIONS: Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes.
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Anti-Hipertensivos , Assistência de Longa Duração , Casas de Saúde , Humanos , Anti-Hipertensivos/uso terapêutico , Masculino , Idoso , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Estados Unidos , Hipertensão/tratamento farmacológico , Desprescrições , United States Department of Veterans AffairsRESUMO
BACKGROUND: Little is known about how often contextual factors such as patient preferences and competing priorities impact prescribing of guideline-recommended medications, or about the extent to which these factors are documented in medical records and available to performance measurement systems. METHODS: Mixed-methods study of 295 veterans aged 50 years and older in 4 VA health care systems who had systolic heart failure and were not prescribed a ß-blocker and/or an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker. Reasons for nontreatment were identified from clinic notes and from interviews with 62 primary care clinicians caring for these patients. These reasons were classified using a published taxonomy. RESULTS: Among 295 patients not receiving guideline-recommended drugs for heart failure, chart review identified biomedical reasons for nonprescribing in 42%-58% of patients and contextual reasons in 11%-17%. Clinician interviews identified twice as many reasons for nonprescribing as chart review (mean 1.6 vs. 0.8 reasons per patient, P<0.001). In these interviews, biomedical reasons for nonprescribing were cited in 50%-70% of patients, and contextual reasons in 64%-70%. The most common contextual reasons were comanagement with other clinicians (32%-35% of patients), patient preferences and nonadherence (15%-24%), and clinician belief that the medication is not indicated in the patient (12%-20%). CONCLUSIONS: Contextual reasons for not prescribing angiotensin converting enzyme inhibitor / angiotensin-receptor blockers and ß-blockers are present in two thirds of patients with heart failure who did not receive these medications, yet are poorly documented in medical records. The structure of medical records should be improved to facilitate documentation of contextual reasons for not providing guideline-recommended care.
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Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Fidelidade a Diretrizes , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Preferência do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Veteranos/psicologia , Veteranos/estatística & dados numéricosAssuntos
Sobreviventes de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/epidemiologia , Idoso , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Próstata/classificação , Neoplasias da Próstata/terapiaRESUMO
Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.
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Pâncreas Exócrino , Transcriptoma , Humanos , Transcriptoma/genética , Pâncreas/metabolismo , Perfilação da Expressão Gênica , Diferenciação Celular/genética , Análise de Célula Única , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
BACKGROUND: Optimal systolic BP (SBP) control in nursing home residents is uncertain, largely because this population has been excluded from clinical trials. We examined the association of SBP levels with the risk of cardiovascular (CV) events and mortality in Veterans Affairs (VA) nursing home residents on different numbers of antihypertensive medications. METHODS: Our study included 36,634 residents aged ≥65 years with a VA nursing home stay of ≥90 days from October 2006-June 2019. SBP was averaged over the first week after admission and divided into categories. Cause-specific hazard ratios (HRs) of SBP categories with CV events (primary outcome) and all-cause mortality (secondary outcome) were examined using Cox regression and multistate modeling stratified by the number of antihypertensive medications used at admission (0, 1 or 2, and ≥3 medications). RESULTS: More than 76% of residents were on antihypertensive therapy and 20% received ≥3 medications. In residents on antihypertensive therapy, a low SBP < 110 mmHg (compared with SBP 130 ~ 149 mmHg) was associated with a greater CV risk (adjusted HR [95% confidence interval]: 1.47 [1.28-1.68] in 1 or 2 medications group, and 1.41 [1.19-1.67] in ≥3 medications group). In residents on no antihypertensives, both low SBP < 110 mmHg and high SBP ≥ 150 mmHg were associated with higher mortality; while in residents receiving any antihypertensives, a low SBP was associated with higher mortality and the highest point estimates were for SBP < 110 mmHg (1.36 [1.28-1.45] in 1 or 2 medications group, and 1.47 [1.31-1.64] in ≥3 medications group). CONCLUSIONS: The associations of SBP with CV and mortality risk varied by the intensity of antihypertensive treatment among VA nursing home residents. A low SBP among those receiving antihypertensives was associated with increased CV and mortality risk, and untreated high SBP was associated with higher mortality. More research is needed on the benefits and harms of SBP lowering in long-term care populations.
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Hipertensão , Hipotensão , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Hipertensão/complicações , Hipotensão/complicações , Casas de SaúdeRESUMO
Importance: Asymptomatic blood pressure (BP) elevations are common in hospitalized older adults, and widespread heterogeneity in the clinical management of elevated inpatient BPs exists. Objective: To examine the association of intensive treatment of elevated inpatient BPs with in-hospital clinical outcomes of older adults hospitalized for noncardiac conditions. Design, Setting, and Participants: This retrospective cohort study examined Veterans Health Administration data between October 1, 2015, and December 31, 2017, for patients aged 65 years or older hospitalized for noncardiovascular diagnoses and who experienced elevated BPs in the first 48 hours of hospitalization. Interventions: Intensive BP treatment following the first 48 hours of hospitalization, defined as receipt of intravenous antihypertensives or oral classes not used prior to admission. Main Outcome and Measures: The primary outcome was a composite of inpatient mortality, intensive care unit transfer, stroke, acute kidney injury, B-type natriuretic peptide elevation, and troponin elevation. Data were analyzed between October 1, 2021, and January 10, 2023, with propensity score overlap weighting used to adjust for confounding between those who did and did not receive early intensive treatment. Results: Among 66â¯140 included patients (mean [SD] age, 74.4 [8.1] years; 97.5% male and 2.6% female; 17.4% Black, 1.7% Hispanic, and 75.9% White), 14â¯084 (21.3%) received intensive BP treatment in the first 48 hours of hospitalization. Patients who received early intensive treatment vs those who did not continued to receive a greater number of additional antihypertensives during the remainder of their hospitalization (mean additional doses, 6.1 [95% CI, 5.8-6.4] vs 1.6 [95% CI, 1.5-1.8], respectively). Intensive treatment was associated with a greater risk of the primary composite outcome (1220 [8.7%] vs 3570 [6.9%]; weighted odds ratio [OR], 1.28; 95% CI, 1.18-1.39), with the highest risk among patients receiving intravenous antihypertensives (weighted OR, 1.90; 95% CI, 1.65-2.19). Intensively treated patients were more likely to experience each component of the composite outcome except for stroke and mortality. Findings were consistent across subgroups stratified by age, frailty, preadmission BP, early hospitalization BP, and cardiovascular disease history. Conclusions and Relevance: The study's findings indicate that among hospitalized older adults with elevated BPs, intensive pharmacologic antihypertensive treatment was associated with a greater risk of adverse events. These findings do not support the treatment of elevated inpatient BPs without evidence of end organ damage, and they highlight the need for randomized clinical trials of inpatient BP treatment targets.
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Anti-Hipertensivos , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Pacientes Internados , Estudos Retrospectivos , HospitalizaçãoRESUMO
BACKGROUND: Performance measures often fail to account for legitimate reasons why patients do not achieve recommended treatment targets. METHODS: We tested a novel performance measurement system for blood pressure (BP) control that was designed to mimic clinical reasoning. This clinically guided approach focuses on (1) exempting patients for whom tight BP control may not be appropriate or feasible and (2) assessing BP over time. Trained abstractors conducted structured chart reviews of 201 adults with hypertension in 2 VA health care systems. Results were compared with traditional methods of performance measurement. RESULTS: Among 201 veterans, 183 (91%) were male, and the mean age was 71±11 years. Using the clinically guided approach, 61 patients (30%) were exempted from performance measurement. The most common reasons for exemption were inadequate opportunity to manage BP (35 patients, 17%) and the use of 4 or more antihypertensive medications (19 patients, 9%). Among patients eligible for performance measurement, there was little agreement on the presence of controlled versus uncontrolled BP when comparing the most recent BP (the traditional approach) with an integrated assessment of BP control (κ 0.14). After accounting for clinically guided exemptions and methods of BP assessment, only 15 of 72 patients (21%) whose last BP was ≥140/90 mm Hg were classified as problematic by the clinically guided approach. CONCLUSIONS: Many patients have legitimate reasons for not achieving tight BP control, and the methods used for BP assessment have marked effects on whether a patient is classified as having adequate or inadequate BP control.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Fidelidade a Diretrizes/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Indicadores de Qualidade em Assistência à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Determinação da Pressão Arterial , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Fatores Socioeconômicos , Estados Unidos , United States Department of Veterans Affairs/estatística & dados numéricosRESUMO
BACKGROUND: Certain classes of antihypertensive medication may have different associations with cognitive impairment. OBJECTIVE: To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care. METHODS: Retrospective cohort study. Long-term care residents aged 65â+âyears admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (Nâ=â589), 'inhibiting' (Nâ=â3,219), or 'mixed' (Nâ=â1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale). RESULTS: Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06). CONCLUSION: For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.