ライフサイエンスコーパス: alcohol use

1 bstance use disorder (excluding cannabis and alcohol use).

2 ied Charlson comorbidity index, smoking, and alcohol use.

3 methylation may provide novel biomarkers of alcohol use.

4 rtality in the United States, are related to alcohol use.

5 environmental contexts associated with prior alcohol use.

6 of NAFLD requires the absence of significant alcohol use.

7 ined by comorbid renal failure and hazardous alcohol use.

8 ive history, health conditions, and nicotine/alcohol use.

9 can be used as the biomarkers for excessive alcohol use.

10 nts and antipsychotics, and reports of heavy alcohol use.

11 tients with a history of heavy and prolonged alcohol use.

12 s and national initiatives to reduce harmful alcohol use.

13 V co-infection, prescriber type, and drug or alcohol use.

14 ediating the addictive properties of chronic alcohol use.

15 patients with moderate or lesser degrees of alcohol use.

16 e profound impact of marriage on problematic alcohol use.

17 rations that drive and/or maintain excessive alcohol use.

18 ta on changes in the prevalences of 12-month alcohol use, 12-month high-risk drinking, 12-month DSM-I

19 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use

20 had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber,

21 ry of tobacco (31.5% vs 16.2%; p = 0.002) or alcohol use (34.6% vs 20.9%; p = 0.009).

22 Rats were trained to consume alcohol using a two-bottle choice or operant self-admini

23 V co-infection, prescriber type, and drug or alcohol use across the United States.

24 y increased the rate of all-cause mortality (alcohol use: adjusted HR 1.62, 95% CI 1.48-1.77; drug us

25 cardiovascular events, diabetes, obesity, or alcohol use (all p<0.01).

26 The prevalence of alcohol use among Finnish liver transplant recipients ha

27 Mice were trained to consume alcohol using an intermittent-access two-bottle-choice d

28 Alcohol use, an independent risk factor for progression

29 Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug us

30 nto an intermediate phenotype vulnerable for alcohol use and addictive disorders.

31 research regarding the relationship between alcohol use and cancer risk and outcomes.

32 y providers about the influence of excessive alcohol use and cancer risks and treatment complications

33 adjustment, there was no association between alcohol use and CVD risk factors (diabetes, hypertension

34 was a positive association between moderate alcohol use and decreased NASH and fibrosis; however, he

35 ive decision-making after chronic adolescent alcohol use and demonstrate its pharmacological reversal

36 ave been repeatedly implicated in studies of alcohol use and dependence.

37 of GSK1521498 as a potential therapeutic for alcohol use and eating disorders.

38 gh interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not s

39 1G hypermethylation with early escalation of alcohol use and increased impulsiveness.

40 Subgroup analyses found alcohol use and smoking to be the largest risk factors f

41 is etiologically associated with tobacco or alcohol use and/or human papillomavirus (HPV) infection.

42 jection drug use, 45% a history of hazardous alcohol use, and 57% a comorbid psychiatric diagnosis.

43 70 youths (51%) initiated moderate to heavy alcohol use, and 67 remained nonusers.

44 a standard evaluation for mood, drug and/or alcohol use, and activities of daily living and a newly

45 se and coronary artery disease, tobacco use, alcohol use, and body mass index were also collected.

46 care, and high levels of injection drug use, alcohol use, and depression remain relevant issues in th

47 , diabetes mellitus, obesity, smoking, heavy alcohol use, and physical inactivity) and with a 2.25-fo

48 chooling </=8 years, smoking, moderate/heavy alcohol use, and plaque rate >/=41%.

49 se of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure

50 etes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE epsilon4 on the rates of cognitive

51 In multivariable analyses adjusted for alcohol use, anticoagulation, hypercholesterolemia, educ

52 Of the patients, 43% reported alcohol use any time after liver transplantation (LT) an

53 horic acid catalyzed fluorination of allylic alcohols using aryl boronic acids as transient directing

54 ry outcomes, such as the likelihood of heavy alcohol use at 65 years of age (odds ratio, 0.68; 95% CI

55 Participants self-reported alcohol use at study entry and then again after 15, 20,

56 Nondrinkers reported no alcohol use at years 15, 20, and 25.

57 erindividual heterogeneity in postdeployment alcohol-use behaviors.

58 After 12 months of alcohol use, blood rhMAOA expression had decreased in an

59 age, race, sex, educational level, smoking, alcohol use, body mass index, and hypertension.

60 els identified 34 predictors contributing to alcohol use by age 18, including several demographic and

61 Heavy alcohol use can lead to progressive liver damage, especi

62 Chronic alcohol use causes persistent changes in synaptic mRNA e

63 ds, with adjustment for age, sex, ethnicity, alcohol use, CD4(+) T-cell count, HCV genotype, gamma-gl

64 ulated the prevalence of the five major HRBs-alcohol use; cigarette smoking, physical inactivity, unh

65 -risk adolescents before they initiate heavy alcohol use could have important clinical and public hea

66 ality, study site, age, sex, smoking status, alcohol use, daily blocks walked, diuretic use, estimate

67 essness, incarceration, substance use, binge alcohol use, depression, and not achieving a suppressed

68 ylative semipinacol rearrangement of allylic alcohols using diaryliodonium salts is reported.

69 res of socioeconomic status and tobacco use, alcohol use, diet, and physical activity.

70 Precision medicine for alcohol use disorder (AUD) allows optimal treatment of t

71 ent directions in medication development for alcohol use disorder (AUD) emphasize the need to identif

72 Alcohol use disorder (AUD) is a common and chronic disor

73 omplex diseases, but has not been applied to alcohol use disorder (AUD) or other psychiatric diseases

74 alcohol use, high-risk drinking, and DSM-IV alcohol use disorder (AUD) represents a major gap in pub

75 Alcohol use disorder (AUD) represents a serious public h

76 s that there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with pos

77 Alcohol use disorder (AUD) runs strongly in families.

78 Alcohol use disorder (AUD) symptoms and drinking behavio

79 cted data on the new DSM-5 classification of alcohol use disorder (AUD) using a reliable, valid, and

80 ine (DA) signaling regulates many aspects of Alcohol Use Disorder (AUD).

81 he relationship between divorce and risk for alcohol use disorder (AUD).

82 shed literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms t

83 onditions, NESARC-were interviewed using the Alcohol Use Disorder and Associated Disabilities Intervi

84 as assessed with a structured interview (the Alcohol Use Disorder and Associated Disabilities Intervi

85 s were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Intervi

86 re measured with a structured interview (the Alcohol Use Disorder and Associated Disabilities Intervi

87 ay be an early indicator of vulnerability to alcohol use disorder and should be carefully assessed as

88 of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methyl

89 e protective effects of marriage on risk for alcohol use disorder are increased in those at high fami

90 Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness,

91 Alcohol use disorder defined by DSM-5 criteria is a high

92 Alcohol use disorder has been linked to dysregulation of

93 ire-9, Generalised Anxiety Disorder-7 scale, Alcohol Use Disorder Identification Test (AUDIT), and se

94 After verbal consent, participants filled in Alcohol Use Disorder Identification Test C and Beck Depr

95 result supported by the dFNC outcome and the alcohol use disorder identification test.

96 Alcohol use disorder in adoptees was significantly predi

97 e associations between marriage and risk for alcohol use disorder in cousins, half siblings, full sib

98 l status and risk for first registration for alcohol use disorder in medical, criminal, and pharmacy

99 h a substantial decline in risk for onset of alcohol use disorder in men (hazard ratio=0.41, 95% CI=0

100 er, while marriage to a spouse with lifetime alcohol use disorder increased risk for subsequent alcoh

101 ohol-seeking behavior.SIGNIFICANCE STATEMENT Alcohol use disorder is a chronic relapsing disorder tha

102 Alcohol use disorder is a heterogeneous syndrome and mea

103 the needs of critically ill patients with an alcohol use disorder is assessed based on available evid

104 First marriage to a spouse with no lifetime alcohol use disorder is associated with a large reductio

105 Alcohol use disorder is one of the leading causes of dis

106 The genetic component of alcohol use disorder is substantial, but monozygotic twi

107 eral lines of evidence indicate that chronic alcohol use disorder leads to increased susceptibility t

108 scored above the screening threshold for an alcohol use disorder on the full Alcohol Use Disorders I

109 Patients with a chronic alcohol use disorder presenting to the ICU may be defici

110 Alcohol use disorder recorded in medical, legal, or phar

111 l use disorder increased risk for subsequent alcohol use disorder registration in both men (hazard ra

112 Alcohol use disorder seemed to have a greater effect in

113 Alcohol use disorder was assessed from medical, criminal

114 e used to determine whether risk factors for alcohol use disorder were associated with the rate of ac

115 tested the hypothesis that risk factors for alcohol use disorder, including family history of alcoho

116 Alcoholism, or alcohol use disorder, is a major public health concern t

117 everal risk factors have been identified for alcohol use disorder, many individuals with these factor

118 ed in individuals with anxiety disorders and alcohol use disorder, the end result of which may be dis

119 ntegrative hub between anxiety disorders and alcohol use disorder, which are commonly co-occurring in

120 tly stronger when the spouse had no lifetime alcohol use disorder, while marriage to a spouse with li

121 s and shows promise as a novel treatment for alcohol use disorder.

122 target for developing novel medications for alcohol use disorder.

123 strongly protect against the development of alcohol use disorder.

124 with than those without a family history of alcohol use disorder.

125 ssociated with a large reduction in risk for alcohol use disorder.

126 e relationship between marriage and risk for alcohol use disorder.

127 se-1G (PPM1G) gene locus was associated with alcohol use disorder.

128 ropathological cortical changes characterize alcohol use disorder.

129 have potential as novel targets for treating alcohol use disorder.SIGNIFICANCE STATEMENT Clinical res

130 : odds ratio [OR], 6.2; 95% CI, 4.1-9.4; any alcohol use disorder: OR, 2.7; 95% CI, 1.9-3.8; any cann

131 the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subject

132 Alcohol-use disorder (AUD) is the most prevalent substan

133 The same pattern was seen for alcohol use disorders (2.23, 95% CI=1.93-2.58; 1.84, 95%

134 the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BE

135 Alcohol use disorders (AUDs) affect people at great indi

136 Alcohol use disorders (AUDs) and anxiety disorders (ADs)

137 Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substan

138 xone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective fo

139 ntal cortex (PFC) may contribute to risk for alcohol use disorders (AUDs).

140 ovides evidence for a role of aldosterone in alcohol use disorders (AUDs).

141 sidered to model compulsive aspects of human alcohol use disorders (AUDs).

142 bstance use disorders were assessed with the Alcohol Use Disorders and Associated Disabilities Interv

143 to a better understanding of the etiology of alcohol use disorders and improve medication development

144 ghtened in children with a family history of alcohol use disorders and is a risk factor for later sub

145 f onset in alcohol use in the development of alcohol use disorders and persistent decision-making def

146 preventable death and illness; and although alcohol use disorders are 50%-60% genetically determined

147 Alcohol use disorders are common among patients admitted

148 Alcohol use disorders are common in developed countries,

149 Alcohol use disorders cause substantial morbidity and ea

150 entiates binge drinkers and individuals with alcohol use disorders from healthy volunteers.

151 ecruited male harmful drinkers defined by an Alcohol Use Disorders Identification Test (AUDIT) score

152 years screening with harmful drinking on the Alcohol Use Disorders Identification Test (AUDIT) were r

153 ing, identification and treatment, using the Alcohol Use Disorders Identification Test (AUDIT-C) in b

154 At this cutoff, the Alcohol Use Disorders Identification Test -C had a sensi

155 cohol Use Disorders Identification Test, the Alcohol Use Disorders Identification Test -C had an area

156 ue gold standard, and the performance of the Alcohol Use Disorders Identification Test -C is likely o

157 o confirm the construct validity of the full Alcohol Use Disorders Identification Test and to evaluat

158 sorders Identification Test-C using the full Alcohol Use Disorders Identification Test as a proxy gol

159 et of hazardous drinking among those with an Alcohol Use Disorders Identification Test consumption su

160 ndrome network studies, 1,037 (92%) had full Alcohol Use Disorders Identification Test data available

161 ion that is comparable with the full 10-item Alcohol Use Disorders Identification Test screening ques

162 Construct validity analysis of the full Alcohol Use Disorders Identification Test supported a th

163 Although a three-factor structure for the Alcohol Use Disorders Identification Test was confirmed

164 Compared with the full Alcohol Use Disorders Identification Test, the Alcohol U

165 uate the performance of the brief three-item Alcohol Use Disorders Identification Test-C using the fu

166 hold for an alcohol use disorder on the full Alcohol Use Disorders Identification Test.

167 individuals with early-life alcohol use for alcohol use disorders in adulthood.

168 a high concentration of middle-aged men with alcohol use disorders in China and to a lesser extent in

169 nd electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were s

170 sents a phenotype linked to vulnerability of alcohol use disorders, and an increase, or 'escalation',

171 the authors identified rates of drug abuse, alcohol use disorders, and criminal behavior in 41,360 S

172 For drug abuse, alcohol use disorders, and criminal behavior, the result

173 parent-offspring resemblance for drug abuse, alcohol use disorders, and criminal behavior, using a no

174 Alcohol abuse and dependence (alcohol use disorders, AUDs) are associated with brain s

175 laced to opportunistically assess and manage alcohol use disorders, but in practice diagnosis and tre

176 icity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history o

177 ood, posttraumatic stress disorder, anxiety, alcohol use disorders, drug use disorders, and self-harm

178 showed that binge drinkers, like those with alcohol use disorders, had elevated premature responding

179 enetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the br

180 key strategy to reduce the treatment gap for alcohol use disorders, one of the leading causes of the

181 ng therapeutic strategy for the treatment of alcohol use disorders, particularly in cases linked to c

182 e the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, un

183 to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis,

184 he development of pharmacotherapies to treat alcohol use disorders, yet little is known regarding how

185 a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this rela

186 Externalizing disorders-drug abuse and alcohol use disorders-demonstrated the third pattern, in

187 be important in vulnerability to developing alcohol use disorders.

188 ould improve clinical care for patients with alcohol use disorders.

189 as a target for pharmacological treatment of alcohol use disorders.

190 reoffending of 50% or more, 88% had drug and alcohol use disorders.

191 inge drinkers and 36 abstinent subjects with alcohol use disorders.

192 OPRM1, has been much studied in relation to alcohol use disorders.

193 ment of neuropsychiatric diseases, including alcohol use disorders.

194 sults do not apply to short-term outcomes or alcohol use disorders.

195 get nociceptin receptors in the treatment of alcohol use disorders.

196 factors, and is correlated with the risk of alcohol use disorders.

197 status of NOP receptors in individuals with alcohol use disorders.

198 dence-based interventions for depression and alcohol-use disorders.

199 assessments, and provided monthly reports of alcohol use during a 12-month follow-up period.

200 Heavy alcohol use during adolescence may alter the trajectory

201 s provide a call for caution regarding heavy alcohol use during adolescence, whether heavy drinking i

202 or identifying youths at risk for initiating alcohol use during adolescence.

203 y cases of preventable disability, and thus, alcohol use during pregnancy should be recognised as a p

204 contribution of other drug use to identified alcohol use effects.

205 Age, education, employment, partner, and alcohol use explained these S&G differences within the N

206 ver, studying the influence of deployment on alcohol use faces 2 complications.

207 th insurance, full-time employment, moderate alcohol use, fewer prior surgeries, fewer comorbid condi

208 nosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of

209 This issue provides a clinical overview of alcohol use, focusing on health benefits, harms, prevent

210 vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood.

211 identified the most important predictors of alcohol use from a large set of demographic, neuropsycho

212 factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietar

213 ndicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is

214 tabolism and cardiovascular risk, with light alcohol use generally being protective while chronic hea

215 omatic carboxylic acids to the corresponding alcohol using glucose, pyruvate, and/or hydrogen as the

216 f diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset.

217 eases in many chronic comorbidities in which alcohol use has a substantial role.

218 Research in alcohol use has revealed a trend in which alcohol consum

219 rom a uniform, reliable, and valid source on alcohol use, high-risk drinking, and DSM-IV alcohol use

220 With few exceptions, increases in alcohol use, high-risk drinking, and DSM-IV AUD between

221 Increases in alcohol use, high-risk drinking, and DSM-IV AUD in the U

222 Twelve-month alcohol use, high-risk drinking, and DSM-IV AUD.

223 s index, physical activity, smoking history, alcohol use, history of myocardial infarction (MI), hist

224 a deployment is associated with increases in alcohol use; however, studying the influence of deployme

225 by body mass index, current smoking, current alcohol use, hypertension, diabetes/impaired fasting glu

226 elf-administration of alcohol in animals and alcohol use in alcohol-dependent patients, but its utili

227 ed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca's subjecti

228 mount of ethanol consumed; and by initiating alcohol use in current abstainers.

229 n to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02-1.04],

230 This study suggests that moderate alcohol use in men is not beneficial for heart function

231 strong recommendation of benefit of moderate alcohol use in NAFLD cannot be made.

232 take and few mechanistic studies of moderate alcohol use in NAFLD exist.

233 hed findings implicating the age of onset in alcohol use in the development of alcohol use disorders

234 on prescriber type, and 88% include drug or alcohol use in their sofosbuvir eligibility criteria, wi

235 Excessive alcohol use in young adults is associated with greater i

236 -naive adolescents to identify predictors of alcohol use initiation by age 18.

237 Alcohol use is a major contributor to the burden of gast

238 We assessed whether alcohol use is associated with CVD risk in patients with

239 Moderate alcohol use is associated with improved insulin sensitiv

240 ern observational studies show that moderate alcohol use is associated with lower cardiovascular dise

241 d phasic dopamine signaling after adolescent alcohol use is attributable to a midbrain circuit, inclu

242 predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the

243 the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in

244 ith NAFLD in midlife, prospectively assessed alcohol use is not associated with significant differenc

245 the primary problems resulting from chronic alcohol use is persistent, maladaptive decision-making t

246 res and a paucity of evidence around harmful alcohol use limit the certainty of these findings.

247 port questionnaires and correlations between alcohol use liver biochemistry and depressive symptoms a

248 prevalence estimates of current tobacco use, alcohol use, low fruit and vegetable intake, low physica

249 accelerate fibrosis progression and moderate alcohol use may increase the risk of hepatocellular carc

250 In contrast to general population findings, alcohol use may not reduce the risk of CVD in patients w

251 Here, we show that adolescent alcohol use may produce maladaptive decision-making thro

252 , medical comorbidities, psychoactive drugs, alcohol use, mental state) tend to vary systematically b

253 se who received LT during childhood reported alcohol use more often and more drinks per occasion.

254 Ongoing injection drug use (PWID) and alcohol use (MSM) were associated with lower awareness.

255 current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison

256 , 2086 (34.4%) reported harmful or hazardous alcohol use, of whom 1082 (50.4%) were dependent, and 38

257 ardiomyopathy, but the influence of moderate alcohol use on cardiac structure and function is largely

258 a critical review of the effect of moderate alcohol use on cardiovascular and liver disease in patie

259 We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of

260 p to ascertain the causal effect of moderate alcohol use on specific factors related to CVD and there

261 fect of brain stimulation on actual drug and alcohol use or relapse.

262 ociations were noted between nurses' weight, alcohol use, or physical activity level and their health

263 CI, 83-99]), history of injection drug use, alcohol use, or psychiatric diagnosis.

264 non-alcoholic fatty liver disease, hazardous alcohol use, or type 2 diabetes, reported higher prevale

265 k taking, mental ill health, and problematic alcohol use (ORs of more than three to six), and stronge

266 e, body mass index, cardiopulmonary disease, alcohol use, pacemaker, cholesterol, cardiac medications

267 ty, family history of hypertension, smoking, alcohol use, physical activity, and body mass index, the

268 Alcohol use, physical activity, reproductive history, an

269 less than two); moderate for smoking, heavy alcohol use, poor self-rated health, cancer, heart disea

270 rimary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restr

271 ent genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Arm

272 aumatic life experiences are associated with alcohol use problems, an association that is likely to b

273 ry FIB-4, entry CD4(+) count, and cumulative alcohol use remained significant.

274 Adolescent alcohol use remains a major public health concern due in

275 reclinical model in rodents, that adolescent alcohol use results in adult risk-taking behavior that p

276 he targets for six risk factors (tobacco and alcohol use, salt intake, obesity, and raised blood pres

277 hus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning proces

278 stment for age, sex, socioeconomic position, alcohol use, smoking, body mass index, and health status

279 , after adjustment for age, body mass index, alcohol use, smoking, exercise, prevalent diabetes and h

280 lood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, a

281 d for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and

282 The F statistic was 77 for ALDH2 on alcohol use, suggesting little weak-instrument bias.

283 ts were interviewed to determine smoking and alcohol use, sunlight exposure, and diet; underwent fund

284 gnificantly higher prevalence of tobacco and alcohol use than did high socioeconomic groups.

285 could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System.

286 drogenative coupling of styrene with primary alcohols using the precatalyst HClRu(CO)(PCy3 )2 modifie

287 ent for the number of years of education and alcohol use, there was a significant increase for cannab

288 matched on a critical confounding variable, alcohol use, to a far greater degree than in previously

289 estyle factors were included: smoking, heavy alcohol use, unhealthy diet and physical inactivity.

290 ge, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol conce

291 by 4.8% in the United Arab Emirates, whereas alcohol use was highest in Russia and accounted for 21.4

292 Alcohol use was independently associated with liver fibr

293 , compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression

294 Light/moderate alcohol use was not substantially associated with accele

295 In women, low educational levels and alcohol use were associated with more wrinkling, whereas

296 Differences in self-reported alcohol use were maintained at the 3-month follow-up.

297 THC and alcohol use were quantified as average exposure per week

298 ts with a long-standing history of excessive alcohol use, whereas NAFLD is encountered commonly in pa

299 te the population's change in postdeployment alcohol use, which ignores previous studies that have do

300 es have assessed the association of moderate alcohol use with cardiovascular outcomes.