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1.
Genes Dev ; 32(15-16): 1035-1044, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30006480

RESUMO

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARγ dramatically affects the oxidation of glutamine. Both glutamine and PPARγ have been implicated in alternative activation (AA) of macrophages, and PPARγ was required for interleukin 4 (IL4)-dependent gene expression and stimulation of macrophage respiration. Indeed, unstimulated macrophages lacking PPARγ contained elevated levels of the inflammation-associated metabolite itaconate and express a proinflammatory transcriptome that, remarkably, phenocopied that of macrophages depleted of glutamine. Thus, PPARγ functions as a checkpoint, guarding against inflammation, and is permissive for AA by facilitating glutamine metabolism. However, PPARγ expression is itself markedly increased by IL4. This suggests that PPARγ functions at the center of a feed-forward loop that is central to AA of macrophages.


Assuntos
Glutamina/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , PPAR gama/fisiologia , Animais , Respiração Celular , Células Cultivadas , Ácidos Graxos/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Interleucina-4/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR gama/genética , Rosiglitazona , Tiazolidinedionas/farmacologia
2.
J Mol Cell Cardiol ; 188: 90-104, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38382296

RESUMO

The role of erythropoietin (EPO) has extended beyond hematopoiesis to include cytoprotection, inotropy, and neurogenesis. Extra-renal EPO has been reported for multiple tissue/cell types, but the physiological relevance remains unknown. Although the EPO receptor is expressed by multiple cardiac cell types and human recombinant EPO increases contractility and confers cytoprotection against injury, whether the heart produces physiologically meaningful amounts of EPO in vivo is unclear. We show a distinct circadian rhythm of cardiac EPO mRNA expression in adult mice and increased mRNA expression during embryogenesis, suggesting physiological relevance to cardiac EPO production throughout life. We then generated constitutive, cardiomyocyte-specific EPO knockout mice driven by the Mlc2v promoter (EPOfl/fl:Mlc2v-cre+/-; EPOΔ/Δ-CM). During cardiogenesis, cardiac EPO mRNA expression and cellular proliferation were reduced in EPOΔ/Δ-CM hearts. However, in adult EPOΔ/Δ- CM mice, total heart weight was preserved through increased cardiomyocyte cross-sectional area, indicating the reduced cellular proliferation was compensated for by cellular hypertrophy. Echocardiography revealed no changes in cardiac dimensions, with modest reductions in ejection fraction, stroke volume, and tachycardia, whereas invasive hemodynamics showed increased cardiac contractility and lusitropy. Paradoxically, EPO mRNA expression in the heart was elevated in adult EPOΔ/Δ-CM, along with increased serum EPO protein content and hematocrit. Using RNA fluorescent in situ hybridization, we found that Epo RNA colocalized with endothelial cells in the hearts of adult EPOΔ/Δ-CM mice, identifying the endothelial cells as a cell responsible for the EPO hyper-expression. Collectively, these data identify the first physiological roles for cardiomyocyte-derived EPO. We have established cardiac EPO mRNA expression is a complex interplay of multiple cell types, where loss of embryonic cardiomyocyte EPO production results in hyper-expression from other cells within the adult heart.


Assuntos
Células Endoteliais , Eritropoetina , Animais , Camundongos , Hiperplasia , Hibridização in Situ Fluorescente , Miócitos Cardíacos , RNA , RNA Mensageiro/genética
3.
J Hum Nutr Diet ; 36(2): 554-565, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35320595

RESUMO

BACKGROUND: Rates of cancer survival are increasing, with more people living with and beyond cancer. Lifestyle recommendations for cancer survivors are based largely on extrapolation from cancer prevention recommendations. This feasibility study was designed to investigate diet and physical activity variables linked to primary prevention and digital behaviour change interventions in cancer survivors and delivered by an oncology dietitian to plan for future research. METHODS: In this 2-month feasibility study, participants who had completed treatment for colorectal cancer were invited to complete online food diaries, underwent physical activity assessment, attended fortnightly telephone consultations with an oncology dietitian and completed an evaluation form. The baseline food diaries were used to help participants pick two lifestyle changes to focus on throughout the intervention. Demographic and clinical data were analysed using descriptive statistics. RESULTS: In total, 996 patients were screened for eligibility; of these, 78 were eligible to approach and 69 were approached, resulting in 20 participants consenting to take part. Overall, the intervention was acceptable with 65% of participants completing an online food diary and 70% engaging with the dietitian over the telephone. The intervention received good feedback, with 100% of those completing the evaluation form reporting they felt supported and found it helpful. CONCLUSIONS: The present study offers preliminary evidence that a lifestyle intervention delivered by an oncology dietitian using digital behaviour change interventions (DBCIs) to cancer survivors is feasible and accepted by participants and providers.


Assuntos
Neoplasias Colorretais , Estilo de Vida , Humanos , Estudos de Viabilidade , Dieta , Exercício Físico , Neoplasias Colorretais/terapia
4.
Telemed J E Health ; 29(6): 795-797, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36383108

RESUMO

The medical environment is on the verge of a dramatic transformation as artificial intelligence (AI) evolves. With the inevitable shift toward AI in health care delivery, there are concerns around its implementation, including ethics, privacy, data representation, and the potential for eliminating physicians. However, AI cannot replicate a physician's knowledge and understanding of the patient as a person and the conditions in which he or she lives. Therefore, provider-patient communication will be paramount in providing safe and effective health care. This piece describes the importance of patient-centered communication and the unintentional move away from this in recent times. We argue that patient-provider communication is vital in the age of AI as it will integrate into the way medicine is practiced, thus leading to more time with the patient to build rapport, trust, and empathy. This will ultimately lead to optimal health-related outcomes.


Assuntos
Inteligência Artificial , Médicos , Feminino , Humanos , Comunicação , Atenção à Saúde , Assistência Centrada no Paciente
5.
Community Ment Health J ; 59(3): 578-594, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36322279

RESUMO

The Sequential Intercept Model has helped conceptualize interventions for people with serious mental illness in the criminal/legal system. This paper operationalizes the Sequential Intercept Model into a 35-item scorecard of behavioral health and legal practices. Using interviews, survey, and observational methods, the scorecard assesses an exploratory sample of 19 counties over 27 independent data collections. A series of ordinary least squares regression models assessed the predictor scores on four jail outcomes: prevalence of serious mental illness, length of stay, connections to treatment, and recidivism. Increases in pre-booking scores showed significant decreases in jail prevalence of serious mental illness at the p < 0.05 level, and post-booking scores and overall scores showed significant positive associations with connections to treatment at the p < 0.05 level, though these were non-significant after correcting for multiple comparisons. Preliminary findings suggest a combination of practices across the Sequential Intercept Model could have synergistic impacts on key jail diversion outcomes.


Assuntos
Transtornos Mentais , Prisioneiros , Psiquiatria , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Liderança , Direito Penal
6.
Am J Physiol Heart Circ Physiol ; 323(6): H1221-H1230, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36331554

RESUMO

Myocardial ischemic injury and its resolution are the key determinants of morbidity or mortality in heart failure. The cause and duration of ischemia in patients vary. Numerous experimental models and methods have been developed to define genetic, metabolic, molecular, cellular, and pathophysiological mechanisms, in addition to defining structural and functional deterioration of cardiovascular performance. The rapid rise of big data, such as single-cell analysis techniques with bioinformatics, machine learning, and neural networking, brings a new level of sophistication to our understanding of myocardial ischemia. This mini-review explores the multifaceted nature of ischemic injury in the myocardium. We highlight recent state-of-the-art findings and strategies to show new directions of high-impact approach to understanding myocardial tissue remodeling. This next age of heart and circulatory physiology research will be more comprehensive and collaborative to uncover the origin, progression, and manifestation of heart failure while strengthening novel treatment strategies.


Assuntos
Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Coração , Miocárdio/metabolismo , Isquemia/metabolismo
7.
Adm Policy Ment Health ; 49(1): 104-115, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34272640

RESUMO

The behavioral health needs, service utilization, and discharge planning provision of veterans in jails have been understudied, yet practitioners must understand each component to ensure veterans' behavioral health needs are met through linkage to culturally-appropriate services. Thus, this study asked: How do veterans differ from non-veterans regarding behavioral health needs, jail-based service engagement, and discharge planning within jails? How do jails identify veterans and are they referred to culturally-appropriate services? In a booking sample across eight jails, this evaluative, cross-sectional study compared veterans to non-veterans by demographics, criminal/legal outcomes, behavioral health needs, and receipt of jail-based behavioral health and discharge planning services. Additionally, the process by which booking officers and jail-based clinicians identify veterans was assessed. Veterans were more likely to be male, older, to have received mental health services prior to their jail stay, and to misuse alcohol. They are less likely to have insecure housing and misuse drugs. No differences existed for length of stay in jail nor recidivism. Veterans were equally likely to receive jail-based behavioral health services, but less likely to receive discharge planning services. While many veterans identified their military status at booking, just over one-third who received services from clinicians were identified as veterans. Of those identified by clinicians, few were referred to culturally-appropriate services as part of their discharge planning. Practitioners in the criminal/legal and mental health systems need to collaborate and develop processes that successfully identify and link veterans to culturally-appropriate services.


Assuntos
Transtornos Mentais , Prisioneiros , Veteranos , Estudos Transversais , Feminino , Humanos , Prisões Locais , Masculino , Transtornos Mentais/terapia , Prisões
8.
J Urol ; 205(4): 967-976, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33350857

RESUMO

PURPOSE: We sought to identify new information evaluating clinically localized prostate cancer therapies. MATERIALS AND METHODS: Bibliographic databases (2013-January 2020), ClinicalTrials.gov and systematic reviews were searched for controlled studies of treatments for clinically localized prostate cancer with duration ≥5 years for mortality and metastases, and ≥1 year for harms. RESULTS: We identified 67 eligible references. Among patients with clinically, rather than prostate specific antigen, detected localized prostate cancer, watchful waiting may increase mortality and metastases but decreases urinary and erectile dysfunction vs radical prostatectomy. Comparative mortality effect may vary by tumor risk and age but not by race, health status, comorbidities or prostate specific antigen. Active monitoring probably results in little to no mortality difference in prostate specific antigen detected localized prostate cancer vs radical prostatectomy or external beam radiation plus androgen deprivation regardless of tumor risk. Metastases were slightly higher with active monitoring. Harms were greater with radical prostatectomy than active monitoring and mixed between external beam radiation plus androgen deprivation vs active monitoring. 3-Dimensional conformal radiation and androgen deprivation plus low dose rate brachytherapy provided small mortality reductions vs 3-dimensional conformal radiation and androgen deprivation but little to no difference on metastases. External beam radiation plus androgen deprivation vs external beam radiation alone may result in small mortality and metastasis reductions in higher risk disease but may increase sexual harms. Few new data exist on other treatments. CONCLUSIONS: Radical prostatectomy reduces mortality vs watchful waiting in clinically detected localized prostate cancer but causes more harms. Effectiveness may be limited to younger men and those with intermediate risk disease. Active monitoring results in little to no mortality difference vs radical prostatectomy or external beam radiation plus androgen deprivation. Few new data exist on other treatments.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Pesquisa Comparativa da Efetividade , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/mortalidade , Conduta Expectante
9.
Proc Natl Acad Sci U S A ; 115(22): E5096-E5105, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760084

RESUMO

Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.


Assuntos
Tecido Adiposo/citologia , Inflamação/fisiopatologia , Macrófagos , Animais , Exossomos/química , Feminino , Humanos , Inflamação/genética , Macrófagos/química , Macrófagos/classificação , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia , Tetraspanina 29/análise , Tetraspanina 29/metabolismo , Transcriptoma/genética
10.
Ann Intern Med ; 172(10): 656-668, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32340037

RESUMO

BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Medicamentos sob Prescrição/farmacologia , Doença de Alzheimer/fisiopatologia , Humanos , Resultado do Tratamento
11.
Am J Community Psychol ; 67(1-2): 7-20, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009671

RESUMO

The overrepresentation of individuals with mental illness in the criminal/legal system is well documented. While professional associations urge diversion towards treatment, little is known about the practices these institutions use to identify this population. One understudied space in the criminal/legal continuum is jails. This exploratory study compares two types of mental health identification at jail booking to assess jail- and community-based service outcomes by identification type (N = 2956): (a) staff observation and (b) a standardized screening instrument. Individuals identified through staff observation were significantly more likely to receive jail- and community-based services, even though current symptomology and substance misuse were both significantly higher for individuals identified only by the screening instrument. These findings point to the importance of jails in providing stabilizing services during incarceration, but further, show the impact that identification practices have on individuals as they transition to the community. Community context showed varied rates of jail staff observations of mental illness, showing greater risks for individuals in rural communities. Implications include a need for system-level changes by instituting evidence-based identification practices in jails, and improving professional collaboration practices between mental health and criminal/legal practitioners as individuals enter and exit jails.


Assuntos
Transtornos Mentais , Prisioneiros , Direito Penal , Humanos , Prisões Locais , Programas de Rastreamento , Transtornos Mentais/diagnóstico , Saúde Mental
12.
Ann Intern Med ; 171(1): 37-50, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31009947

RESUMO

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). Limitation: No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Conclusion: Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Alendronato/efeitos adversos , Alendronato/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Esquema de Medicação , Duração da Terapia , Feminino , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/prevenção & controle , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/uso terapêutico
13.
Aging Male ; 22(1): 1-11, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29394114

RESUMO

We conducted a systematic review to evaluate the efficacy and adverse effects of newer drugs used to treat lower urinary tract symptoms (LUTS). The drugs were either Food and Drug Administration (FDA) approved for benign prostatic hyperplasia (BPH) or not FDA approved for BPH but have been evaluated for treatment of BPH since 2008. We searched bibliographic databases through September 2017. We included randomized controlled trials (RCTs) lasting one month or longer published in English. Outcomes of interest were LUTS assessed by validated measures. Efficacy was interpreted using established thresholds indicating clinical significance that identified the minimal detectable difference. Twenty-three unique, generally short-term, RCTs evaluating over 9000 participants were identified. Alpha-blocker silodosin and phosphodiesterase type 5 inhibitor tadalafil were more effective than placebo in improving LUTS (moderate strength evidence) but these drugs had more adverse effects, including abnormal ejaculation (silodosin). Anticholinergics were only effective versus placebo when combined with an alpha-blocker. Evidence was generally low strength or insufficient for other drugs. Evidence was insufficient to assess long-term efficacy, prevention of symptom progression, need for surgical intervention, or long-term adverse effects. Longer trials are needed to assess the effect of these therapies on response rates using established minimal detectable difference thresholds, disease progression, and harms.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Inibidores da Fosfodiesterase 5/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/efeitos adversos , Quimioterapia Combinada , Humanos , Masculino , Inibidores da Fosfodiesterase 5/efeitos adversos , Hiperplasia Prostática/complicações , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Ann Intern Med ; 168(1): 63-68, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29255842

RESUMO

Background: Structured activities to stimulate brain function-that is, cognitive training exercises-are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated. Purpose: To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI). Data Sources: Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches. Study Selection: Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia. Data Extraction: Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed. Data Synthesis: Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported. Limitation: Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias. Conclusion: In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient. Primary Funding Source: Agency for Healthcare Research and Quality.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Disfunção Cognitiva/psicologia , Demência/psicologia , Humanos
15.
Ann Intern Med ; 168(1): 39-51, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29255847

RESUMO

Background: Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. Purpose: To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Data Sources: Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. Study Selection: English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Data Extraction: Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Data Synthesis: Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). Limitation: High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Conclusion: Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Primary Funding Source: Agency for Healthcare Research and Quality.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Hormônios/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico
16.
Ann Intern Med ; 168(1): 52-62, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29255909

RESUMO

Background: Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. Purpose: To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Data Sources: Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Data Extraction: Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or ß-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, ß-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Limitation: Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Conclusion: Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI. Primary Funding Source: Agency for Healthcare Research and Quality.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Medicamentos sem Prescrição/uso terapêutico , Humanos
17.
Ann Intern Med ; 168(1): 30-38, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29255839

RESUMO

Background: The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. Purpose: To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Data Sources: Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. Data Extraction: Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. Limitation: Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. Conclusion: Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). Primary Funding Source: Agency for Healthcare Research and Quality.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/fisiopatologia , Exercício Físico , Idoso , Humanos , Pessoa de Meia-Idade
18.
Prev Sci ; 20(6): 833-843, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30284159

RESUMO

The oversaturation of alcohol outlets can have disastrous public health consequences. The goal of this study was to evaluate the potential impact of new zoning legislation, TransForm Baltimore on locations of alcohol outlets. More specifically, the study sought to determine the effect of the new zoning code on the potential redistribution of alcohol outlets and also provide empirical support for the need to actively monitor redistribution of outlets to avoid further inequitable oversaturation in disadvantaged neighborhoods. Data on off-premise alcohol outlets (e.g., packaged goods stores) were obtained from the Board of Liquor License Commissioners for Baltimore City. The alcohol outlets were geocoded and assigned to zoning parcels. Churches and schools were also geocoded. The alcohol outlets were also assigned to census tracts to calculate socioeconomic statuses. One hundred seventy-two of the 263 off-premise packaged goods stores (PGS) were in violation of the new zoning law. TransForm will reduce the land parcels available to alcohol outlets by 27.2%. Areas containing non-conforming PGS were more likely to have a higher percentage of Black residents, single parent-families, unemployment, household poverty, and vacancy compared to Baltimore City averages and areas without non-conforming PGS. Planning enforcement efforts need to accompany related laws to prevent/reduce overconcentration of PGS in disadvantaged neighborhoods.


Assuntos
Bebidas Alcoólicas/provisão & distribuição , Comércio/legislação & jurisprudência , Saúde Pública , Consumo de Bebidas Alcoólicas , Humanos , Mid-Atlantic Region , Características de Residência , População Urbana
19.
J Community Psychol ; 47(1): 63-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30506926

RESUMO

This research investigated the relationship between alcohol outlet density (AOD) and life expectancy, as mediated by community violence and community disadvantage. We used linear regression models to assess bivariate and multivariate relationships. There was a negative bivariate association between liquor store density and average life expectancy (ß = -7.3370, p < 0.001). This relationship was partially attenuated when controlling for community disadvantage and fully attenuated when controlling for community violence. Bars/taverns (i.e., on-premise) were not associated with average life expectancy (ß = -0.589, p = 0.220). Liquor store density is associated with higher levels of community disadvantage and higher rates of violence, both of which are associated with lower life expectancies. Future research, potential intervention, and current related policies are discussed.


Assuntos
Bebidas Alcoólicas/provisão & distribuição , Comércio/estatística & dados numéricos , Expectativa de Vida/tendências , Pobreza , Violência , Baltimore , Estudos Transversais , Feminino , Humanos , Masculino , População Urbana
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