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1.
Artigo em Inglês | MEDLINE | ID: mdl-38353166

RESUMO

OBJECTIVE: We utilized national claims-based data to identify the change in odds of diagnosis of ALS following possible-ALS-symptoms-and whether the change varies in urban/rural areas. METHODS: Insurance claims were obtained from the Merative MarketScan databases, 2001-2021 in the United States. Individuals with incident ALS were identified and matched on age, sex, and enrollment period to individuals without ALS. For all individuals, claims for 8 possible-ALS-symptoms in the time before any ALS diagnosis were identified. We then used conditional logistic regression to estimate the odds of being diagnosed with ALS following these symptoms and whether the association varied by urban/rural location. RESULTS: 19,226 individuals with ALS were matched to 96,126 controls. Patients with ALS were more likely to live in an urban area (87.0% vs 84.5%). Of those with ALS 84% had 1+ of our 8 possible-ALS-symptom compared to 51% of controls. After adjustment for confounders, having possible-ALS-symptoms increased the odds of a future ALS diagnosis by nearly 5-fold. A dose-response pattern was present with increasing odds as the number of symptoms increased. In all models, urban areas were associated with increased odds of diagnosis with ALS while the effect of having a symptom was smaller in urban places. Urban cases of ALS are diagnosed at younger ages. CONCLUSIONS: These results suggest symptoms may appear and be noted years before the diagnosis of ALS. Additionally, rural patients are diagnosed at later ages with a greater dependence on symptoms than urban patients. These results highlight potential improvements for screening for ALS.

2.
Pharmacotherapy ; 44(2): 110-121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37926925

RESUMO

BACKGROUND: Prescription opioids have contributed to the rise in opioid-related overdoses and deaths. The presence of opioids within households may increase the risk of overdose among family members who were not prescribed an opioid themselves. Larger quantities of opioids may further increase risk. OBJECTIVES: To determine the risk of opioid overdose among individuals who were not prescribed an opioid but were exposed to opioids prescribed to other family members in the household, and evaluate the risk in relation to the total morphine milligram equivalents (MMEs) present in the household. METHODS: We conducted a cohort study using a large database of commercial insurance claims from 2001 to 2021. For inclusion in the cohort, we identified individuals not prescribed an opioid in the prior 90 days from households with two or more family members, and determined the total MMEs prescribed to other family members. Individuals were stratified into monthly enrollment strata defined by household opioid exposure and other confounders. A generalized linear model was used to estimate incidence rate ratios (IRRs) for overdose. RESULTS: Overall, the incidence of overdose among enrollees in households where a family member was prescribed an opioid was 1.73 (95% confidence interval [CI]: 1.67-1.78) times greater than households without opioid prescriptions. The risk of overdose increased continuously with the level of potential MMEs in the household from an IRR of 1.23 (95% CI: 1.16-1.32) for 1-100 MMEs to 4.67 (95% CI: 4.18-5.22) for >12,000 MMEs. The risk of overdose associated with household opioid exposure was greatest for ages 1-2 years (IRR: 3.46 [95% CI: 2.98-4.01]) and 3-5 years (IRR: 3.31 [95% CI: 2.75-3.99]). CONCLUSIONS: The presence of opioids in a household significantly increases the risk of overdose among other family members who were not prescribed an opioid. Higher levels of MMEs, either in terms of opioid strength or quantity, were associated with increased levels of risk. Risk estimates may reflect accidental poisonings among younger family members.


Assuntos
Overdose de Drogas , Overdose de Opiáceos , Humanos , Analgésicos Opioides/efeitos adversos , Estudos de Coortes , Overdose de Drogas/epidemiologia , Overdose de Drogas/tratamento farmacológico , Prescrições , Família , Padrões de Prática Médica
4.
NPJ Parkinsons Dis ; 9(1): 32, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864060

RESUMO

Terazosin is an α1-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson's disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α1-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.

5.
JAMA Netw Open ; 5(10): e2234269, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190731

RESUMO

Importance: Acute appendicitis is a common cause of abdominal pain and the most common reason for emergency surgery in several countries. Increased cases during summer months have been reported. Objective: To investigate the incidence of acute appendicitis by considering local temperature patterns in geographic regions with different climate over several years. Design, Setting, and Participants: This cohort study used insurance claims data from the MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database from January 1, 2001, to December 31, 2017. The cohort included individuals at risk for appendicitis who were enrolled in US insurance plans that contribute data to the MarketScan databases. Cases of appendicitis in the inpatient, outpatient, and emergency department settings were identified using International Classification of Diseases, Ninth Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. Local weather data were obtained for individuals living in a metropolitan statistical area (MSA) from the Integrated Surface Database. Associations were characterized using a fixed-effects generalized linear model based on a negative binomial distribution. The model was adjusted for age, sex, and day of week and included fixed effects for year and MSA. The generalized linear model was fit with a piecewise linear model by searching each 0.56 °C in temperature for change points. To further isolate the role of temperature, observed temperature was replaced with the expected temperature and the deviation of the observed temperature from the expected temperature for a given city on a given day of year. Data were analyzed from October 1, 2021, to July 31, 2022. Main Outcomes and Measures: The primary outcome was the daily number of appendicitis cases in a given city stratified by age and sex, with mean temperature in the MSA over the previous 7 days as the independent variable. Results: A total of 450 723 744 person-years at risk and 689 917 patients with appendicitis (mean [SD] age, 35 [18] years; 347 473 male [50.4%] individuals) were included. Every 5.56 °C increase in temperature was associated with a 1.3% increase in the incidence of appendicitis (incidence rate ratio [IRR], 1.01; 95% CI, 1.01-1.02) when temperatures were 10.56 °C or lower and a 2.9% increase in incidence (IRR, 1.03; 95% CI, 1.03-1.03) for temperatures higher than 10.56 °C. In terms of temperature deviations, a higher-than-expected temperature increase greater than 5.56 °C was associated with a 3.3% (95% CI, 1.0%-5.7%) increase in the incidence of appendicitis compared with days with near-0 deviations. Conclusions and Relevance: Results of this cohort study observed seasonality in the incidence of appendicitis and found an association between increased incidence and warmer weather. These results could help elucidate the mechanism of appendicitis.


Assuntos
Apendicite , Doença Aguda , Adulto , Idoso , Apendicite/epidemiologia , Estudos de Coortes , Humanos , Incidência , Masculino , Medicare , Estações do Ano , Estados Unidos/epidemiologia , Tempo (Meteorologia)
6.
Mov Disord ; 37(11): 2210-2216, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36054705

RESUMO

BACKGROUND: Terazosin (TZ) and closely related α1-adrenergic receptor antagonists (doxazosin [DZ] and alfuzosin [AZ]) enhance glycolysis and reduce neurodegeneration in animal models. Observational evidence in humans from several databases supports this finding; however, a recent study has suggested that tamsulosin, the comparator medication, increases the risk of Parkinson's disease. AIMS: We consider a different comparison group of men taking 5α-reductase inhibitors (5ARIs) as a new, independent comparison allowing us to both obtain new estimates of the association between TZ/DZ/AZ and Parkinson's disease outcomes and validate tamsulosin as an active comparator. METHODS: Using the Truven Health Analytics Marketscan database, we identified men without Parkinson's disease, newly started on TZ/DZ/AZ, tamsulosin, or 5ARIs. We followed these matched cohorts to compare the hazard of developing Parkinson's disease. We conducted sensitivity analyses using variable duration of lead-in to mitigate biases introduced by prodromal disease. RESULTS: We found that men taking TZ/DZ/AZ had a lower hazard of Parkinson's disease than men taking tamsulosin (hazard ratio (HR) = 0.71, 95% CI [confidence interval]: 0.65-0.77, n = 239,888) and lower than men taking 5ARIs (HR = 0.84, 95% CI: 0.75-0.94, n = 129,116). We found the TZ/DZ/AZ versus tamsulosin HR to be essentially unchanged with up to 5 years of lead-in time; however, the TZ/DZ/AZ versus 5ARI effect became attenuated with longer lead-in durations. CONCLUSIONS: These data suggest that men using TZ/DZ/AZ have a somewhat lower risk of developing Parkinson's disease than those using tamsulosin and a slightly lower risk than those using 5ARIs. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Hiperplasia Prostática , Masculino , Animais , Humanos , Tansulosina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/uso terapêutico , Glicólise
7.
Parkinsonism Relat Disord ; 94: 79-83, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894470

RESUMO

BACKGROUND: Impaired brain energy metabolism is a key feature of Parkinson's disease (PD). Terazosin (TZ) binds phosphoglycerate kinase 1 and stimulates its activity, which enhances glycolysis and increases ATP levels. Preclinical and epidemiologic data suggest that TZ may be neuroprotective in PD. We aimed to assess target engagement and safety of TZ in people with PD. METHODS: We performed a 12-week pilot study in people with PD. Participants were randomized to receive 5 mg TZ or placebo. Participants and study personnel were blinded. We assessed TZ target engagement by measuring brain ATP with 31P-magnetic resonance spectroscopy (MRS) and whole blood ATP with a luminescence assay. Robust linear regression models compared changes between groups controlling for baseline brain and blood ATP levels, respectively. We also assessed clinical measures of PD and adverse events. RESULTS: Thirteen participants were randomized. Mild dizziness/lightheadedness was more common in the TZ group, and three participants taking TZ dropped out because of dizziness and/or orthostatic hypotension. Compared to the placebo group, the TZ group had a significant increase in the ratio of ßATP to inorganic phosphate in the brain. The TZ group also had a significant increase in blood ATP levels compared to the placebo group (p < 0.01). CONCLUSIONS: This pilot study suggests that TZ may engage its target and change ATP levels in the brain and blood of people with PD. Further studies may be warranted to test the disease-modifying potential of TZ.


Assuntos
Doença de Parkinson , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/uso terapêutico , Tontura , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Projetos Piloto , Prazosina/análogos & derivados
8.
J Alzheimers Dis ; 84(4): 1447-1452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690147

RESUMO

Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer's disease (AD) is an independent risk factor for COVID-19 case fatality rate. In a retrospective cohort study, we identified 387,841 COVID-19 patients through TriNetX. After adjusting for demographics and comorbidities, we found that AD patients had higher odds of dying from COVID-19 compared to patients without AD (Odds Ratio: 1.20, 95%confidence interval: 1.09-1.32, p < 0.001). Interestingly, we did not observe increased mortality from COVID-19 among patients with vascular dementia. These data are relevant to the evolving COVID-19 pandemic.


Assuntos
Doença de Alzheimer , COVID-19 , Doença de Alzheimer/complicações , Doença de Alzheimer/mortalidade , COVID-19/complicações , COVID-19/mortalidade , Demência Vascular/complicações , Humanos , Estudos Retrospectivos , Fatores de Risco
9.
Prev Med Rep ; 23: 101426, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34178586

RESUMO

Physical activity is important for preventing obesity and diabetes, but most obese and pre-diabetic patients are not physically active. We developed a Fitbit-based game called MapTrek that promotes walking. We recruited obese and pre-diabetic patients. Half were randomly assigned to the control group and given a Fitbit alone. The others were given a Fitbit plus MapTrek. The MapTrek group participated in 6 months of weekly virtual races. Each week, participants were placed in a race with 9 others who achieved a similar number of steps in the previous week's race. Participants moved along the virtual route by the steps recorded on their Fitbit and received daily walking challenges via text message. Text messages also had links to the race map and leaderboard. We used a Bayesian mixed effects model to analyze the number of steps taken during the intervention. A total of 192 (89%) participants in the control group and 196 (91%) in the MapTrek group were included in the analyses. MapTrek significantly increased step counts when it began: MapTrek participants walked almost 1,700 steps more than the control group on the first day of the intervention. We estimate that there is a 97% probability that the effect of MapTrek is at least 1,000 additional steps per day throughout the course of the 6-month intervention and that MapTrek participants would have walked an additional 81 miles, on average, before the effect ended. Our MapTrek intervention led to significant extra walking by the MapTrek participants.

10.
J Phys Act Health ; 18(7): 851-857, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039774

RESUMO

BACKGROUND: Regular physical activity is crucial for healthy aging, but older adults are the least active age group. This study explored the feasibility, acceptability, and efficacy of a multilevel mHealth intervention for increasing physical activity of older adults living in a retirement community. METHODS: Participants included 54 older adults (mean age = 81.2 y, 77.8% female, 98.1% white) living in a retirement community. Participants received a Fitbit Zip and access to a multilevel mHealth physical activity intervention (MapTrek Residential) for 8 weeks. Physical activity (in steps per day) and intervention compliance (days worn) were measured objectively with the Fitbit for 12 weeks (8-wk intervention plus 4-wk follow-up). Psychosocial outcomes (social support, self-efficacy, and outcome expectations) were assessed at baseline and 8 weeks. Acceptability outcomes were assessed with an open-ended process evaluation survey and focus groups. Descriptive statistics and linear mixed models were used to examine intervention effects. RESULTS: Participants increased daily steps from 5438 steps per day at baseline (95% CI, 4620 to 6256) to 6201 steps per day (95% CI, 5359 to 7042) at week 8 (P < .0001) but this was not maintained at 12 weeks (P = .92). CONCLUSIONS: Our multilevel mHealth physical activity intervention was effective for increasing physical activity older adults over 8 weeks. Additional research focused on maintaining physical activity gains with this approach is warranted.


Assuntos
Aposentadoria , Telemedicina , Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Feminino , Monitores de Aptidão Física , Humanos , Masculino , Inquéritos e Questionários
11.
JAMA Neurol ; 78(4): 407-413, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523098

RESUMO

Importance: Parkinson disease (PD) is a common neurodegenerative disease. A treatment that prevents or delays development of PD is a critical unmet need. Terazosin and closely related drugs were recently discovered to enhance glycolysis and reduce PD progression in animal models and human clinical databases. Objective: To determine whether use of terazosin, doxazosin, and alfuzosin is associated with a decreased risk of developing PD. Design, Setting, and Participants: This cohort study used active comparator control and propensity score-matched data from Danish nationwide health registries, including the Danish National Prescription Registry, the Danish National Patient Registry, and the Danish Civil Registration System, from January 1996 to December 2017 and data from the Truven Health Analytics MarketScan database from January 2001 to December 2017. Men without PD who newly initiated terazosin/doxazosin/alfuzosin therapy or tamsulosin therapy, which is used for a similar indication (benign prostatic hyperplasia or unspecified urinary problems) but does not enhance glycolysis, and had at least 1 year of follow-up after medication start were included. In Denmark, the database included all residents, while the Truven database is a compilation of insurance claims across the US. Data were analyzed from February 2019 to July 2020. Exposures: Patients who used terazosin/doxazosin/alfuzosin vs tamsulosin. Additional dose-response analyses were carried out. Main Outcomes and Measures: Differences in the hazard of developing PD identified by diagnoses or use of PD-specific medications between patients who ever used terazosin/doxazosin/alfuzosin or tamsulosin. Results: A cohort of 52 365 propensity score-matched pairs of terazosin/doxazosin/alfuzosin and tamsulosin users were identified in the Danish registries, of which all were male and the mean (SD) age was 67.9 (10.4) years, and 94 883 propensity score-matched pairs were identified in the Truven database, of which all were male and the mean (SD) age was 63.8 (11.1) years. Patients in the Danish cohort who used terazosin/doxazosin/alfuzosin had a hazard ratio (HR) for developing PD of 0.88 (95% CI, 0.81-0.98), and patients in the Truven cohort had an HR of 0.63 (95% CI, 0.58-0.69). There was a dose-response association with short-duration, medium-duration, and long-duration use of terazosin/doxazosin/alfuzosin users having a decreasing HR in both the Danish cohort (short: HR, 0.95; 95% CI, 0.84-1.07; medium: HR, 0.88; 95% CI, 0.77-1.01; long: HR, 0.79; 95% CI, 0.66-0.95) and Truven cohort (short: HR, 0.70; 95% CI, 0.64-0.76; medium: HR, 0.58; 95% CI, 0.52-0.64; long: HR, 0.46; 95% CI, 0.36-0.57). Conclusions and Relevance: These data suggest that users of terazosin/doxazosin/alfuzosin are at lower hazard of developing PD compared with users of tamsulosin. Future work is needed to further assess this association.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Glicólise/efeitos dos fármacos , Doença de Parkinson/epidemiologia , Doença de Parkinson/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais/tendências , Dinamarca/epidemiologia , Doxazossina/administração & dosagem , Feminino , Seguimentos , Glicólise/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Prazosina/administração & dosagem , Prazosina/análogos & derivados , Quinazolinas/administração & dosagem , Sistema de Registros , Fatores de Risco , Tansulosina/administração & dosagem , Estados Unidos/epidemiologia
12.
J Urol ; 205(2): 500-506, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32945727

RESUMO

PURPOSE: The incidence of urinary tract infections is seasonal, peaking in summer months. One possible mechanism for the observed seasonality of urinary tract infections is warmer weather. MATERIALS AND METHODS: We identified all urinary tract infection cases located in approximately 400 metropolitan statistical areas in the contiguous United States between 2001 and 2015 using the Truven Health MarketScan® databases. A total of 167,078,882 person-years were included in this data set and a total of 15,876,030 urinary tract infection events were identified by ICD-9 code 599.0. Weather data for each metropolitan statistical area and date were obtained from the National Centers for Environmental Information. We computed the mean temperature during the period 0 to 7 days prior to the urinary tract infection diagnosis. We used a quasi-Poisson generalized linear model. The primary outcome was the number of urinary tract infections each day in a metropolitan statistical area in each age group. Covariates considered included age group, day of week, year and the temperature during the previous 7 days. RESULTS: Warmer weather increases the risk of urinary tract infections among women treated in outpatient settings in a dose-response fashion. On days when the prior week's average temperature was between 25 and 30C, the incidence of urinary tract infections was increased by 20% to 30% relative to when the prior week's temperature was 5 to 7.5C. CONCLUSIONS: The incidence of urinary tract infections increases with the prior week's temperature. Our results indicate that warmer weather is a risk factor for urinary tract infections. Furthermore, as temperatures rise, the morbidity attributable to urinary tract infections may increase.


Assuntos
Estações do Ano , Temperatura , Infecções Urinárias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos , Adulto Jovem
13.
Contemp Clin Trials ; 98: 106169, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33038500

RESUMO

BACKGROUND: New approaches are needed to better monitor blood pressure (BP) between physician visits, especially for patients in rural areas or for those who lack transportation. We have developed a custom-built bi-directional texting platform for home BP measurements that can then be managed by clinical pharmacists located remotely. The purpose of this study is to evaluate whether the BP texting approach combined with a pharmacist-based intervention improves BP management and to determine if the approach is cost effective. METHODS: This study is a randomized, prospective trial in four primary care offices that serve patients in rural areas. Subjects will receive standardized research BP measurements at baseline, 6 and 12 months. The primary outcome will be differences between the intervention and control group in mean systolic BP at 12 months. Secondary outcomes will include systolic BP at 6 months; diastolic BP at 6 and 12 months, number of medication changes and costs. CONCLUSIONS: This study plans to enroll subjects through 2022, follow-up will be completed in 2023 and results will be available in 2024. This study will provide information on whether a combined approach using texting of home BP values and a pharmacist-based telehealth services can improve BP control.


Assuntos
Hipertensão , Envio de Mensagens de Texto , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Farmacêuticos , Estudos Prospectivos
15.
Nutrients ; 12(9)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867053

RESUMO

BACKGROUND: It is widely unknown why respiratory infections follow a seasonal pattern. Variations in ultraviolet B (UVB) light during seasons affects cutaneous synthesis of vitamin D3. Serum vitamin D concentration influences the expression of airway surface liquid (ASL) antimicrobial peptides such as LL-37. OBJECTIVE: We sought to determine the effect of seasons on serum vitamin D levels and ASL antimicrobial activity. METHODS: Forty participants, 18-60 years old, were randomized 1:1 to receive 90 days of 1000 IU vitamin D3 or placebo. We collected ASL via bronchoscopy and measured serum 25(OH) vitamin D from participants before and after intervention across seasons. We measured ASL antimicrobial activity by challenging samples with bioluminescent Staphylococcus aureus and measured relative light units (RLUs) after four minutes. We also investigated the role of LL-37 using a monoclonal neutralizing antibody. RESULTS: We found that participants, prior to any intervention, during summer-fall (n = 20) compared to winter-spring (n = 20) had (1) decreased live bacteria after challenge (5542 ± 175.2 vs. 6585 ± 279 RLU, p = 0.003) and (2) higher serum vitamin D (88.25 ± 24.25 vs. 67.5 ± 45.25 nmol/L, p = 0.026). Supplementation with vitamin D3 increased vitamin D levels and restored ASL antimicrobial activity only during the winter-spring. The increased ASL antimicrobial activity seen during the summer-fall was abrogated by adding the LL-37 neutralizing antibody. CONCLUSION: ASL kills bacteria more effectively during the summer-fall compared to the winter-spring. Supplementation of vitamin D during winter-spring restores ASL antimicrobial activity by increasing the expression of antimicrobial peptides including LL-37.


Assuntos
Antibacterianos/metabolismo , Colecalciferol/sangue , Sistema Respiratório/metabolismo , Estações do Ano , Vitaminas/sangue , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta , Adulto Jovem
16.
Pharmacotherapy ; 40(9): 978-983, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32677113

RESUMO

Hydroxychloroquine combined with azithromycin has been investigated for activity against coronavirus disease 2019 (COVID-19), but concerns about adverse cardiovascular (CV) effects have been raised. This study evaluated claims data to determine if risks for CV events were increased with hydroxychloroquine alone or combined with azithromycin. We identified data from 43,752 enrollees that qualified for analysis. The number of CV events increased by 25 (95% confidence interval [CI]: 8, 42, p=0.005) per 1000 people per year of treatment with hydroxychloroquine alone compared with pretreatment levels and by 201 (95% CI: 145, 256, p<0.001) events per 1000 people per year when individuals took hydroxychloroquine and azithromycin. These rates translate to an additional 0.34 (95% CI: 0.11, 0.58) CV events per 1000 patients placed on a 5-day treatment with hydroxychloroquine monotherapy and 2.75 (95% CI: 1.99, 3.51) per 1000 patients on a 5-day treatment with both hydroxychloroquine and azithromycin. The rate of adverse events increased with age following exposure to hydroxychloroquine alone and combined with azithromycin. For females aged 60 to 79 years prescribed hydroxychloroquine, the rate of adverse CV events was 0.92 per 1000 patients on 5 days of therapy, but it increased to 4.78 per 1000 patients when azithromycin was added. The rate of adverse CV events did not differ significantly from zero for patients 60 years of age or younger. These data suggest that hydroxychloroquine with or without azithromycin is likely safe in individuals under 60 years of age if they do not have additional CV risks. However, the combination of hydroxychloroquine and azithromycin should be used with extreme caution in older patients.


Assuntos
Azitromicina/efeitos adversos , Tratamento Farmacológico da COVID-19 , Cardiotoxicidade/etiologia , Hidroxicloroquina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Azitromicina/administração & dosagem , Cardiotoxicidade/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
17.
J Expo Sci Environ Epidemiol ; 30(5): 778-784, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461549

RESUMO

BACKGROUND: Americans spend most of their time indoors. Indoor particulate matter (PM) 2.5 µm and smaller (PM2.5) concentrations often exceed ambient concentrations. Therefore, we tested whether the use of an air purifying device (electrostatic precipitator, ESP) could reduce PM2.5 in homes of smokers with and without respiratory exacerbations, compared with baseline. METHODS: We assessed PM2.5 concentrations in homes of subjects with and without a recent (≤3 years) history of respiratory exacerbation. We compared PM2.5 concentrations during 1 month of ESP use with those during 1 month without ESP use. RESULTS: Our study included 19 subjects (53-80 years old), nine with a history of respiratory exacerbation. Geometric mean (GM) PM2.5 and median GM daily peak PM2.5 were significantly lower during ESP deployment compared with the equivalent time-period without the ESP (GSD = 0.50 and 0.37 µg/m3, respectively, p < 0.001). PM2.5 in homes of respiratory exacerbators tended (p < 0.14) to be higher than PM2.5 in homes of those without a history of respiratory exacerbation. CONCLUSIONS: Subjects with a history of respiratory exacerbation tended to have higher mean, median, and mean peak PM2.5 concentrations compared with homes of subjects without a history of exacerbations. The ESP intervention reduced in-home PM2.5 concentrations, demonstrating its utility in reducing indoor exposures. NOVELTY OF STUDY: Our work characterizes PM air pollution concentrations in homes of study subjects with and without respiratory exacerbations. We demonstrate that PM concentrations tend to be higher in homes of participants with respiratory exacerbations, and that the use of an inexpensive air purifier resulted in significantly lower daily average PM concentrations than when the purifier was not present. Our results provide a helpful intervention strategy for purifying indoor air and may be useful for susceptible populations.


Assuntos
Filtros de Ar , Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Humanos , Iowa , Pessoa de Meia-Idade , Material Particulado/análise , Fumantes
18.
J Clin Invest ; 129(10): 4539-4549, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524631

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.


Assuntos
Glicólise/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Prazosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Progressão da Doença , Dopamina/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Fosfoglicerato Quinase/metabolismo , Prazosina/farmacologia , Ratos
19.
J Clin Hypertens (Greenwich) ; 21(10): 1463-1470, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503408

RESUMO

The authors examined whether using home BP measurements collected via a custom-built bi-directional-texting platform incorporated into patients' electronic medical records would lead to treatment calibration and improved BP management. Patients were randomized to either the intervention group and collected home measurements based on reminders and reported via bi-directional texting, or to the control group, with home BP measurement reporting via standard practice (eg, phone, electronic medical record portal) and instructed to return 7 morning and 7 evening BP measurements. Outcomes included number of BP measurements submitted, the number of medication changes, reduction in BP, and BP control. 72% of the intervention group submitted at least 14 readings, compared with 45% of the control group. BP control improved in both groups. However, the authors found no statistically significant difference in BP or the number of BP-medication changes at 1, 3, or 6 months compared with the control group.


Assuntos
Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Envio de Mensagens de Texto/instrumentação , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , Registros Eletrônicos de Saúde , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
20.
Artigo em Inglês | MEDLINE | ID: mdl-31337001

RESUMO

Acute bouts of uninterrupted sitting has been associated with discomfort and fatigue in adult populations. However, little is known regarding the impact of uninterrupted sitting on such outcomes among college students. Understanding these relations would be useful for informing best practice and future interventions. The present study explored the relation between uninterrupted sitting and perceived levels of physical discomfort and sleepiness among college students in a real classroom setting. We recruited 54 undergraduate students enrolled in a single class at a Midwestern university. Participants remained seated throughout a 2.5 h lecture while completing the Stanford Sleepiness Scale (SSS) and General Comfort Scale (GCS) every 15 min. Linear mixed effect model analyses were used to determine the relations between the independent and dependent variables and the duration at which students reported significant impairments in discomfort and/or sleepiness. Classroom sitting time was associated with increases in discomfort (r = 0.28, p < 0.01) and sleepiness (r = 0.30, p < 0.01). Students reported significant impairments in discomfort and sleepiness after 75 and 15 min, respectively. These findings support further research into the acceptability, feasibility and efficacy of interventions designed to interrupt classroom sitting on discomfort, sleepiness and measures of academic performance.


Assuntos
Fadiga , Postura Sentada , Estudantes , Desempenho Acadêmico , Adolescente , Adulto , Feminino , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Universidades , Adulto Jovem
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