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1.
Ann Intern Med ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31711094

RESUMO

The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed to promote the conduct of, and provide guidance for, predictive analyses of heterogeneity of treatment effects (HTE) in clinical trials. The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risk with versus without the intervention, taking into account all relevant patient attributes simultaneously, to support more personalized clinical decision making than can be made on the basis of only an overall average treatment effect. The authors distinguished 2 categories of predictive HTE approaches (a "risk-modeling" and an "effect-modeling" approach) and developed 4 sets of guidance statements: criteria to determine when risk-modeling approaches are likely to identify clinically meaningful HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. They discuss limitations of these methods and enumerate research priorities for advancing methods designed to generate more personalized evidence. This explanation and elaboration document describes the intent and rationale of each recommendation and discusses related analytic considerations, caveats, and reservations.

2.
Ann Intern Med ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31711134

RESUMO

Heterogeneity of treatment effect (HTE) refers to the nonrandom variation in the magnitude or direction of a treatment effect across levels of a covariate, as measured on a selected scale, against a clinical outcome. In randomized controlled trials (RCTs), HTE is typically examined through a subgroup analysis that contrasts effects in groups of patients defined "1 variable at a time" (for example, male vs. female or old vs. young). The authors of this statement present guidance on an alternative approach to HTE analysis, "predictive HTE analysis." The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risks with versus without the intervention, taking into account all relevant patient attributes simultaneously. The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed using a multidisciplinary technical expert panel, targeted literature reviews, simulations to characterize potential problems with predictive approaches, and a deliberative process engaging the expert panel. The authors distinguish 2 categories of predictive HTE approaches: a "risk-modeling" approach, wherein a multivariable model predicts the risk for an outcome and is applied to disaggregate patients within RCTs to define risk-based variation in benefit, and an "effect-modeling" approach, wherein a model is developed on RCT data by incorporating a term for treatment assignment and interactions between treatment and baseline covariates. Both approaches can be used to predict differential absolute treatment effects, the most relevant scale for clinical decision making. The authors developed 4 sets of guidance: criteria to determine when risk-modeling approaches are likely to identify clinically important HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. The PATH Statement, together with its explanation and elaboration document, may guide future analyses and reporting of RCTs.

3.
Curr Dev Nutr ; 3(10): nzz109, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31667463

RESUMO

Apples and pears contain nutrients that have been linked to cardiovascular health. We conducted a systematic review and meta-analysis to summarize related research. Medline, Cochrane Central, and Commonwealth Agricultural Bureau databases were searched for publications on apple or pear intake and cardiovascular disease (CVD)/ cardiometabolic disease (CMD). Studies in adults (healthy or at risk for CVD) that quantified apple or pear intake were included. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. In total, 22 studies were eligible including 7 randomized controlled trial, 1 nonrandomized trial, and 14 prospective observational studies. In RCTs, apple intake significantly decreased BMI, but made no difference in body weight, serum lipids, blood glucose, or blood pressure. In observational studies, apple or pear intake significantly decreased risk of cerebrovascular disease, cardiovascular death, type 2 diabetes mellitus, and all-cause mortality. No association was reported for cerebral infarction or intracerebral hemorrhage. In conclusion, apple or pear intake significantly decreased BMI and risk for CVD outcomes.

4.
Am J Clin Nutr ; 110(5): 1067-1078, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504087

RESUMO

BACKGROUND: Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution. OBJECTIVE: We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk. METHODS: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence. RESULTS: Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n = 5) and stroke (n = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR. CONCLUSIONS: Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose-response RCTs. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782.

5.
Adv Nutr ; 10(6): 1076-1088, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243439

RESUMO

Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: -10.69 mg/dL; 95% CI: -16.75, -4.63 mg/dL), LDL cholesterol (summary net change: -5.83 mg/dL; 95% CI: -9.91, -1.75 mg/dL); body weight (summary net change: -1.39 kg; 95% CI: -2.49, -0.30 kg), HDL cholesterol (summary net change: -1.26 mg/dL; 95% CI: -2.47, -0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: -6.67 mg/dL; 95% CI: -12.63, -0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.

6.
Endocr Pract ; 25(4): 366-378, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720342

RESUMO

Objective: Hyponatremia decreases bone mineral density and is a major risk factor for fragility fractures. Objectives of our systematic review and meta-analysis were to analyze the overall effects of hyponatremia on bone fractures, osteoporosis, and mortality. Methods: We extracted data from Medline, Cochrane Central, and EMBASE 1960-2017 and conference abstracts from 2007-2017. We included studies with data on serum sodium, fractures, bone density, or diagnoses of osteoporosis. Studies were independently reviewed by two authors and assessed for bias using the Newcastle-Ottawa scale. Random effect models meta-analysis was used when at least three studies reported the same outcome measures. We reported summary odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 26 studies for qualitative analysis. Fifteen studies were included in the meta-analysis to evaluate the effects of hyponatremia on fractures, four studies for bone mineral density changes, and six for mortality. Hyponatremia increased the odds of fractures at all sites (summary OR, 2.34 [95% CI, 1.86, 2.96]. There was an increase in the odds of osteoporosis (summary OR, 2.67 [95% CI, 2.07, 3.43]). Mortality risk among the included studies remained high (summary OR, 1.31 [95% CI, 1.16, 1.47]). Conclusion: Our meta-analysis confirms a statistically significant association of hyponatremia with bone fractures and osteoporosis along with higher mortality. Long-term prospective studies evaluating the impact of correcting hyponatremia on bone health, fractures, and mortality are required. Abbreviations: AVP = arginine vasopressin; CI = confidence interval; CKD = chronic kidney disease; OR = odds ratio; SIADH = syndrome of inappropriate antidiuretic hormone.


Assuntos
Fraturas Ósseas , Hiponatremia , Osteoporose , Densidade Óssea , Humanos , Estudos Prospectivos
7.
Syst Rev ; 7(1): 100, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021626

RESUMO

BACKGROUND: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. METHODS: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. RESULTS: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. CONCLUSION: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs. SYSTEMATIC REVIEW REGISTRATION: At present, evidence mapping is not eligible for registration on the international prospective register of systematic reviews (i.e., PROSPERO).


Assuntos
Bebidas , Sistema Cardiovascular/efeitos dos fármacos , Flavonoides/administração & dosagem , Alimentos , Ensaios Clínicos Controlados Aleatórios como Assunto , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cacau/química , Doenças Cardiovasculares/tratamento farmacológico , Suplementos Nutricionais
8.
Artigo em Inglês | MEDLINE | ID: mdl-29997889

RESUMO

Background: Identifying risk factors predicting acquisition of resistant Pseudomonas aeruginosa will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant P. aeruginosa among hospitalized patients. Methods: MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant P. aeruginosa, among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar. Results: Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) P. aeruginosa and 26 publications (29 studies) examined resistant P. aeruginosa. The acquisition of MDR P. aeruginosa, as compared with non-MDR P. aeruginosa, was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible P. aeruginosa was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR P. aeruginosa compared with non-P. aeruginosa was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant P. aeruginosa compared with susceptible P. aeruginosa, was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36). Conclusions: Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant P. aeruginosa. These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.


Assuntos
Antibacterianos/uso terapêutico , Cuidados Críticos/estatística & dados numéricos , Infecção Hospitalar/transmissão , Unidades de Terapia Intensiva/estatística & dados numéricos , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/isolamento & purificação , Quinolonas/uso terapêutico , Fatores de Risco , Vancomicina/uso terapêutico
9.
BMJ Open ; 8(5): e017641, 2018 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-29804057

RESUMO

OBJECTIVE: Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis. STUDY DESIGN: Systematic review and reanalysis of multiperson N-of-1 studies. DATA SOURCES: Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English. STUDY SELECTION: N-of-1 studies of pharmacological interventions with at least two subjects. DATA SYNTHESIS: Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data. RESULTS: We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes. CONCLUSIONS: Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed.


Assuntos
Ensaios Clínicos como Assunto , Estudos Cross-Over , Medicina Baseada em Evidências/métodos , Humanos , Modelos Estatísticos , Terapêutica/estatística & dados numéricos , Resultado do Tratamento
10.
Am J Clin Nutr ; 107(4): 523-536, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635493

RESUMO

Background: Nutrients in avocados are associated with cardiovascular benefits. Objective: The aim of this study was to determine the effect of avocado intake on cardiovascular disease (CVD) risk with the use of a systematic review and meta-analysis. Design: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched from 1946 through September 2017 for publications on avocado intake and CVD risk. All designs except for cross-sectional studies that evaluated avocado intake were included. Two investigators independently screened citations and extracted data. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. Results: Of 18 eligible studies (481 subjects), 7 studies compared avocado intake with no intake, 3 studies compared avocado plus monounsaturated fat intake with a control, and 8 studies reported data for qualitative synthesis. In 7 studies, avocado intake significantly increased HDL cholesterol (summary net change: 2.84 mg/dL; 95% CI: 0.18, 5.49 mg/dL), with significant heterogeneity. This remained consistent in sensitivity and subgroup analyses. There was no significant difference between avocado intake and the control for the outcomes of serum total cholesterol (TC), LDL cholesterol, triglycerides (TGs), ratios of TC to HDL cholesterol and LDL cholesterol to HDL cholesterol, and body weight. In qualitative synthesis, there was no significant difference between groups for blood glucose (2 studies), homeostasis model assessment (1 of 2 studies), oxidized LDL (2 studies), high-sensitivity C-reactive protein (2 studies), or apolipoprotein B (2 studies) or, in 1 study each, for body mass index, systolic and diastolic blood pressure, arterial compliance, fibrinogen, interleukin 6, tumor necrosis factor α, and serum nitric oxide. No studies reported incident clinical outcomes of CVD, including myocardial infarction, stroke, and other clinical endpoints. Conclusions: Avocado intake resulted in no difference in serum TC, LDL-cholesterol, and TG concentrations, but it did increase serum HDL-cholesterol concentrations, with significant heterogeneity. The association between avocado intake and CVD risk should be confirmed by well-conducted prospective observational studies or long-term trials.


Assuntos
Dieta , Comportamento Alimentar , Cardiopatias/prevenção & controle , Persea , Cardiopatias/etiologia , Humanos , Lipídeos/sangue , Fatores de Risco
11.
Diagn Progn Res ; 1: 20, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31093549

RESUMO

Background: Clinical predictive models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision-making and individualize care. The Tufts Predictive Analytics and Comparative Effectiveness (PACE) CPM Registry is a comprehensive database of cardiovascular disease (CVD) CPMs. The Registry was last updated in 2012, and there continues to be substantial growth in the number of available CPMs. Methods: We updated a systematic review of CPMs for CVD to include articles published from January 1990 to March 2015. CVD includes coronary artery disease (CAD), congestive heart failure (CHF), arrhythmias, stroke, venous thromboembolism (VTE), and peripheral vascular disease (PVD). The updated Registry characterizes CPMs based on population under study, model performance, covariates, and predicted outcomes. Results: The Registry includes 747 articles presenting 1083 models, including both prognostic (n = 1060) and diagnostic (n = 23) CPMs representing 183 distinct index condition/outcome pairs. There was a threefold increase in the number of CPMs published between 2005 and 2014, compared to the prior 10-year interval from 1995 to 2004. The majority of CPMs were derived from either North American (n = 455, 42%) or European (n = 344, 32%) populations. The database contains 265 CPMs predicting outcomes for patients with coronary artery disease, 196 CPMs for population samples at risk for incident CVD, and 158 models for patients with stroke. Approximately two thirds (n = 701, 65%) of CPMs report a c-statistic, with a median reported c-statistic of 0.77 (IQR, 0.05). Of the CPMs reporting validations, only 333 (57%) report some measure of model calibration. Reporting of discrimination but not calibration is improving over time (p for trend < 0.0001 and 0.39 respectively). Conclusions: There is substantial redundancy of CPMs for a wide spectrum of CVD conditions. While the number of CPMs continues to increase, model performance is often inadequately reported and calibration is infrequently assessed. More work is needed to understand the potential impact of this literature.

13.
Am J Nephrol ; 44(3): 206-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27576318

RESUMO

BACKGROUND: Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients. METHODS: Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts. RESULTS: Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death. CONCLUSIONS: Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.


Assuntos
Disponibilidade Biológica , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/uso terapêutico , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Transplante de Rim , Ciclosporina/farmacocinética , Ciclosporina/uso terapêutico , Medicamentos Genéricos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Equivalência Terapêutica
14.
Ann Intern Med ; 165(9): 635-649, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27536808

RESUMO

Background: Atherosclerotic renal artery stenosis (ARAS) is associated with high blood pressure (BP), decreased kidney function, renal replacement therapy (RRT), and death. Purpose: To compare benefits and harms of percutaneous transluminal renal angioplasty with stent placement (PTRAS) versus medical therapy alone in adults with ARAS. Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1993 to 16 March 2016; gray literature; and prior systematic reviews. Study Selection: Randomized, controlled trials (RCTs); nonrandomized, comparative studies (NRCSs); single-group studies; and selected case reports that reported all-cause and cardiovascular mortality, RRT, kidney function, BP, and adverse events. Data Extraction: Six researchers extracted data on design, interventions, outcomes, and study quality into a Web-based database. Data Synthesis: Eighty-three studies met eligibility criteria. In 5 of 7 RCTs, PTRAS and medical therapy led to similar BP control in patients with ARAS, and no RCTs showed statistically significant differences in kidney function, mortality, RRT, cardiovascular events, or pulmonary edema. Eight NRCSs had more variable results, finding mostly no significant differences in mortality, RRT, or cardiovascular events but heterogeneous effects on kidney function and BP. Procedure-related adverse events were rare, and medication-related adverse events were not reported. Two RCTs found no patient characteristics that were associated with outcomes with either PTRAS or medical therapy. Single-group studies found various but inconsistent factors that predict outcomes. Case reports provided examples of clinical improvement after PTRAS in patients with acute decompensation. Limitation: Limited clinical applicability and power in RCTs, and possible publication bias and lack of adjusted analyses in NRCSs. Conclusion: The strength of evidence regarding the relative benefits and harms of PTRAS versus medical therapy alone for patients with ARAS is low. Studies have generally focused on patients with less severe ARAS. Primary Funding Source: Agency for Healthcare Research and Quality.


Assuntos
Obstrução da Artéria Renal/terapia , Adulto , Angioplastia/métodos , Anti-Hipertensivos/uso terapêutico , Pesquisa Comparativa da Efetividade , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/tratamento farmacológico , Obstrução da Artéria Renal/mortalidade , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Stents
15.
J Am Heart Assoc ; 5(5)2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27151514

RESUMO

BACKGROUND: Guidelines for stroke prevention recommend development of sex-specific stroke risk scores. Incorporating sex in Clinical Prediction Models (CPMs) may support sex-specific clinical decision making. To better understand their potential to guide sex-specific care, we conducted a field synopsis of the role of sex in stroke-related CPMs. METHODS AND RESULTS: We identified stroke-related CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Database, a systematic summary of cardiovascular CPMs published from January 1990 to May 2012. We report the proportion of models including the effect of sex on stroke incidence or prognosis, summarize the directionality of the predictive effects of sex, and explore factors influencing the inclusion of sex. Of 92 stroke-related CPMs, 30 (33%) contained a coefficient for sex or presented sex-stratified models. Only 12/58 (21%) CPMs predicting outcomes in patients included sex, compared to 18/30 (60%) models predicting first stroke (P<0.0001). Sex was most commonly included in models predicting stroke among a general population (69%). Female sex was consistently associated with reduced mortality after ischemic stroke (n=4) and higher risk of stroke from arrhythmias or coronary revascularization (n=5). Models predicting first stroke versus outcomes among patients with stroke (odds ratio=5.75, 95% CI 2.18-15.14, P<0.001) and those developed from larger versus smaller sample sizes (odds ratio=4.58, 95% CI 1.73-12.13, P=0.002) were significantly more likely to include sex. CONCLUSIONS: Sex is included in a minority of published CPMs, but more frequently in models predicting incidence of first stroke. The importance of sex-specific care may be especially well established for primary prevention.


Assuntos
Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Acidente Vascular Cerebral/epidemiologia , Feminino , Humanos , Incidência , Masculino , Razão de Chances , Prognóstico , Medição de Risco , Tamanho da Amostra , Fatores Sexuais
16.
Circ Cardiovasc Qual Outcomes ; 9(2 Suppl 1): S8-15, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26908865

RESUMO

BACKGROUND: Several widely used risk scores for cardiovascular disease (CVD) incorporate sex effects, yet there has been no systematic summary of the role of sex in clinical prediction models (CPMs). To better understand the potential of these models to support sex-specific care, we conducted a field synopsis of sex effects in CPMs for CVD. METHODS AND RESULTS: We identified CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Registry, a comprehensive database of CVD CPMs published from January 1990 to May 2012. We report the proportion of models including sex effects on CVD incidence or prognosis, summarize the directionality of the predictive effects of sex, and explore factors influencing the inclusion of sex. Of 592 CVD-related CPMs, 193 (33%) included sex as a predictor or presented sex-stratified models. Sex effects were included in 78% (53/68) of models predicting incidence of CVD in a general population, versus only 35% (59/171), 21% (12/58), and 17% (12/72) of models predicting outcomes in patients with coronary artery disease, stroke, and heart failure, respectively. Among sex-including CPMs, women with heart failure were at lower mortality risk in 8 of 8 models; women undergoing revascularization for coronary artery disease were at higher mortality risk in 10 of 12 models. Factors associated with the inclusion of sex effects included the number of outcome events and using cohorts at-risk for CVD (rather than with established CVD). CONCLUSIONS: Although CPMs hold promise for supporting sex-specific decision making in CVD clinical care, sex effects are included in only one third of published CPMs.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Incidência , Masculino , Modelos Teóricos , Caracteres Sexuais
17.
Ann Intern Med ; 164(3): 164-75, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26550776

RESUMO

BACKGROUND: Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes. PURPOSE: To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide). DATA SOURCES: MEDLINE, EMBASE, and Ovid Healthstar (inception through 30 June 2015), and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the first quarter of 2015). STUDY SELECTION: 4 researchers double-screened articles for longitudinal studies that compared women with and without breast implants and reported long-term health outcomes of interest. DATA EXTRACTION: 4 researchers extracted data on participant and implant characteristics, analytic methods, and results. DATA SYNTHESIS: 32 studies (in 58 publications) met eligibility criteria. Random-effects model meta-analyses of effect sizes were conducted when feasible. For most outcomes, there was at most only a single adequately adjusted study, which usually found no significant associations. There were possible associations with decreased risk for primary breast and endometrial cancers and increased risks for lung cancer, rheumatoid arthritis, Sjögren syndrome, and Raynaud syndrome. Evidence on breast implants and other outcomes either was limited or did not exist. LIMITATION: The evidence was most frequently not specific to silicone gel implants, and studies were rarely adequately adjusted for potential confounders. CONCLUSION: The evidence remains inconclusive about any association between silicone gel implants and long-term health outcomes. Better evidence is needed from existing large studies, which can be reanalyzed to clarify the strength of associations between silicone gel implants and health outcomes. PRIMARY FUNDING SOURCE: The Plastic Surgery Foundation.


Assuntos
Implantes de Mama , Nível de Saúde , Géis de Silicone , Artrite Reumatoide/epidemiologia , Doenças Autoimunes/epidemiologia , Implantes de Mama/efeitos adversos , Doenças do Tecido Conjuntivo/epidemiologia , Feminino , Humanos , Transtornos da Lactação , Saúde Mental , Neoplasias/epidemiologia , Doença de Raynaud/epidemiologia , Saúde Reprodutiva , Fatores de Risco , Síndrome de Sjogren/epidemiologia
18.
BMC Infect Dis ; 15: 395, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26423743

RESUMO

BACKGROUND: The rapid global spread of multi-resistant bacteria and loss of antibiotic effectiveness increases the risk of initial inappropriate antibiotic therapy (IAT) and poses a serious threat to patient safety. We conducted a systematic review and meta-analysis of published studies to summarize the effect of appropriate antibiotic therapy (AAT) or IAT against gram-negative bacterial infections in the hospital setting. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched until May 2014 to identify English-language studies examining use of AAT or IAT in hospitalized patients with Gram-negative pathogens. Outcomes of interest included mortality, clinical cure, cost, and length of stay. Citations and eligible full-text articles were screened in duplicate. Random effect models meta-analysis was used. RESULTS: Fifty-seven studies in 60 publications were eligible. AAT was associated with lower risk of mortality (unadjusted summary odds ratio [OR] 0.38, 95 % confidence interval [CI] 0.30-0.47, 39 studies, 5809 patients) and treatment failure (OR 0.22, 95 % CI 0.14-0.35; 3 studies, 283 patients). Conversely, IAT increased risk of mortality (unadjusted summary OR 2.66, 95 % CI 2.12-3.35; 39 studies, 5809 patients). In meta-analyses of adjusted data, AAT was associated with lower risk of mortality (adjusted summary OR 0.43, 95 % CI 0.23-0.83; 6 studies, 1409 patients). Conversely, IAT increased risk of mortality (adjusted summary OR 3.30, 95 % CI 2.42-4.49; 16 studies, 2493 patients). A limited number of studies suggested higher cost and longer hospital stay with IAT. There was considerable heterogeneity in the definition of AAT or IAT, pathogens studied, and outcomes assessed. DISCUSSION: Using a large set of studies we found that IAT is associated with a number of serious consequences,including an increased risk of hospital mortality. Infections caused by drug-resistant, Gram-negative organisms represent a considerable financial burden to healthcare systems due to the increased costs associated with the resources required to manage the infection, particularly longer hospital stays. However, there were insufficient data that evaluated AAT for the outcome of costs among patients with nosocomialGram-negative infections. CONCLUSIONS: IAT in hospitalized patients with Gram-negative infections is associated with adverse outcomes. Technological advances for rapid diagnostics to facilitate AAT along with antimicrobial stewardship, surveillance, infection control, and prevention is needed.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Bases de Dados Factuais , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Negativas/patologia , Hospitalização , Humanos , Tempo de Internação , Razão de Chances , Análise de Sobrevida
19.
Dermatol Online J ; 21(6)2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26158355

RESUMO

In recent years, several case reports and outbreaks reported occurrence of non-tuberculous mycobacteria (NTM) infections within 6 months after receiving a tattoo in healthy individuals. NTM species (e.g., Chelonae, Fortuitum, Hemophillum, and Abscessus) are widespread in the environment and it is often suspected that contamination may occur through unsterile instrumentation or unsterile water used for diluting tattoo ink to dilute color. In reported cases, lesions were mainly restricted to a single color 'gray' part of the tattoo. Mycobacterium Chelonae was the most common cause of tattoo associated NTM infections. Less than 50% of the case reports tested tattoo ink for acid fast bacilli stains and cultures. Subjects required treatment with either clarithromycin alone or in combination with quinolones for 6 to 9 months. An increase in NTM skin infections in healthy individuals after tattooing indicates the need for sterile standards during tattooing and improved local and regional regulatory oversight.


Assuntos
Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/etiologia , Tatuagem/efeitos adversos , Antibacterianos/uso terapêutico , Humanos , Tinta , Infecções por Micobactéria não Tuberculosa/microbiologia , Tatuagem/normas
20.
Circ Cardiovasc Qual Outcomes ; 8(4): 368-75, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26152680

RESUMO

BACKGROUND: Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease, there are numerous CPMs available although the extent of this literature is not well described. METHODS AND RESULTS: We conducted a systematic review for articles containing CPMs for cardiovascular disease published between January 1990 and May 2012. Cardiovascular disease includes coronary heart disease, heart failure, arrhythmias, stroke, venous thromboembolism, and peripheral vascular disease. We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. Seven hundred seventeen (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions, including 215 CPMs for patients with coronary artery disease, 168 CPMs for population samples, and 79 models for patients with heart failure. There are 77 distinct index/outcome pairings. Of the de novo models in this database, 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. CONCLUSIONS: There is an abundance of CPMs available for a wide assortment of cardiovascular disease conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood.


Assuntos
Doenças Cardiovasculares/epidemiologia , Modelos Teóricos , Medição de Risco/métodos , Saúde Global , Humanos , Morbidade/tendências , Fatores de Risco
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