Faculty Bibliography

A strong positive association has been observed between circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles < 0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top versus bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4-Q1 = 1.96, 95% CI = 1.46-2.64, ptrend <0.0001; ER+/PR-: ORQ4-Q1 = 0.82, 95% CI = 0.40-1.68, ptrend = 0.51; ER-/PR+: ORQ4-Q1 = 3.23, 95% CI =0.48-21.9, ptrend = 0.26; ER-/PR-: ORQ4-Q1 = 1.15, 95% CI = 0.63-2.09, ptrend = 0.60. The association was observed for both pre- (ORQ4-Q1 = 1.35, 95% CI= 1.05-1.73) and post-menopausal (ORQ4-Q1 =1.61, 95% CI = 1.03 - 2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

BACKGROUND:Binge drinking among older adults has increased in the past decade. Binge drinking is associated with unintentional injuries, medical conditions, and lower health-related quality of life. No studies have characterized multimorbidity among older binge drinkers. METHODS:We examined past 30-day binge alcohol use and lifetime medical conditions among adults age ≥50 from the National Survey on Drug Use and Health from 2005 to 2014. Self-reported lifetime prevalence of 13 medical conditions and medical multimorbidity (≥2 diseases) among binge drinkers were compared to non-binge drinkers. Multivariable logistic regression models were used to examine correlates of binge alcohol use among older adults with medical multimorbidity. RESULTS:Among adults aged ≥50, 14.4% reported past-month binge drinking. Estimated prevalence of medical multimorbidity was lower (21.4%) among binge drinkers than non-binge drinkers (28.3%; p < 0.01). Binge drinkers were more likely to use tobacco and illegal drugs than non-binge drinkers (ps < 0.001). In the adjusted model, among older adults with multimorbidity, higher income (AOR = 1.44, p < 0.05), past-month tobacco use (AOR = 2.55, p < 0.001) and substance use disorder for illegal drugs (AOR = 1.80, p < 0.05) was associated with increased odds of binge alcohol use. CONCLUSION/CONCLUSIONS:The prevalence of multimorbidity was lower among current binge drinkers compared to non-binge drinkers, possibly because older adults in good health are apt to drink more than adults in poorer health. Current use of tobacco and substance use disorder were associated with an increased risk for binge drinking among older adults with multimorbidity. Binge drinking by older adults with multimorbidity may pose significant health risks especially with the concurrent use of other substances.

Background: Methamphetamine (MA) use remains a major public health concern around the world. Recent findings suggest that buprenorphine may be helpful for cocaine use reduction. Moreover, animal studies described reduced dopamine peak effect following MA use, due to the administration of low dose buprenorphine. Objectives: This study examined the effectiveness of buprenorphine with brief cognitive behavioral therapy on MA use disorder. Methods: The study was conducted in an outpatient substance abuse treatment center in Qazvin, Iran. Nineteen MA users received buprenorphine for 24 weeks combined with brief cognitive behavioral therapy in an outpatient substance abuse treatment program, three times per week, as a before and after non - randomization study. Clinical outcomes included treatment retention, MA use, degree of MA dependency and craving, quality of life, cognitive abilities questionnaire, addiction severity and also adverse events. Data was analyzed by performing repeated measures analysis and the Friedman test for nonparametric variables. Results: Fifteen participants completed the study during six months and frequency of MA use was significantly decreased at 24 weeks (P < 0.001). There were also significant reductions in craving (P < 0.001), degree of MA dependence (P < 0.001), and improvements in quality of life, cognitive ability, and some subscales of addiction severity. Conclusions: The results of this preliminary clinical study demonstrated that buprenorphine could potentially attenuateMAcraving and alternate rewarding effects of MAand had promising effects on cognitive impairment. Furthermore, buprenorphine can be considered as a harm reduction intervention in some communities, in which the people, as a result of cultural beliefs, do not accept a therapy, which only consists of counseling and no medications.

OBJECTIVE:Our objective was to determine specialist physicians' attitudes and practices regarding disclosure of pre-referral errors. SUMMARY BACKGROUND DATA/BACKGROUND:Physicians are encouraged to disclose their own errors to patients. However, no clear professional norms exist regarding disclosure when physicians discover errors in diagnosis or treatment that occurred at other institutions before referral. METHODS:We conducted semistructured interviews of cancer specialists from 2 National Cancer Institute-designated Cancer Centers. We purposively sampled specialists by discipline, sex, and experience-level who self-described a >50% reliance on external referrals (n = 30). Thematic analysis of verbatim interview transcripts was performed to determine physician attitudes regarding disclosure of pre-referral medical errors; whether and how physicians disclose these errors; and barriers to providing full disclosure. RESULTS:Participants described their experiences identifying different types of pre-referral errors including errors of diagnosis, staging and treatment resulting in adverse events ranging from decreased quality of life to premature death. The majority of specialists expressed the belief that disclosure provided no benefit to patients, and might unnecessarily add to their anxiety about their diagnoses or prognoses. Specialists had varying practices of disclosure including none, non-verbal, partial, event-dependent, and full disclosure. They identified a number of barriers to disclosure, including medicolegal implications and damage to referral relationships, the profession's reputation, and to patient-physician relationships. CONCLUSIONS:Specialist physicians identify pre-referral errors but struggle with whether and how to provide disclosure, even when clinical circumstances force disclosure. Education- or communication-based interventions that overcome barriers to disclosing pre-referral errors warrant development.

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m². Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m² and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m² and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7-6.4% (37-47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when ß-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs.

Early childhood represents a period of rapid cognitive developmental change in executive function (EF) skills along with a variety of related cognitive processes, including processing speed. This leads to interpretational challenges in that children's performance on EF tasks reflects more than EF skills per se. We tested whether the inclusion of a brief measure of simple reaction time (SRT) during EF assessments could help to partially address this challenge. Data were drawn from a cross-sectional convenience sample of 830 preschool-aged children. Individual differences in SRT were significantly associated with performance on all tasks (R²s = .09-.26); slower performance on the SRT task was associated with poorer performance on each EF task. Age-related differences in individual EF tasks were reduced by approximately one half after accounting for age-related differences in SRT, and EF task scores were less coherent (i.e., less strongly intercorrelated with each other) after the removal of SRT. Age-related differences in EF were smaller (Cohen ds = 1.36 vs. 0.78), and poverty-related differences in EF were larger (Cohen ds = 0.30 vs. 0.46) after accounting for SRT-related variation. Finally, consistent with previous studies, SRT-related differences in fluid reasoning were mediated by EF skills. Results are discussed with respect to using a brief measure of SRT to partially address the problem of measurement impurity at the level of individual EF tasks.

OBJECTIVE:To investigate the association between individual and area-level socioeconomic status and hypertension risk among individuals later in life. METHODS:We used Cox proportional hazards models to examine the association of socioeconomic status with incident hypertension using race-specific neighborhood socioeconomic status, median household income, and education among 3372 participants (mean age, 61 years) from the Atherosclerosis Risk in Communities Study at Visit 4 (1996-1998). Incident hypertension was defined as self-reported diagnosis or reported use of antihypertensive medications. RESULTS:Over a median follow-up time of 9.4 years, there were 1874 new cases of hypertension (62.1 per 1000 person-years). Overall, being in high as compared with low socioeconomic status categories was associated with a lower risk of developing hypertension in late life, with hazard ratios (95% confidence intervals) of 0.87 (0.77-0.98) for high neighborhood socioeconomic status tertile, 0.79 (0.69-0.90) for high individual income, and 0.75 (0.63-0.89) for college education after adjustment for traditional risk factors. These findings were consistent and robust whenever accounting for competing risks of all-cause mortality. No significant interactions by race and age (dichotomized at age 65) were observed. CONCLUSION:Among participants free of hypertension in midlife, high neighborhood and individual socioeconomic status are associated with a decreased risk of incident hypertension. Our findings support population-level interventions, such as blood pressure screening at senior centers and faith-based organizations, that are tailored to shift the distribution of blood pressure and reduce hypertension health inequalities among older adults.

Heavy cannabis use is associated with a wide array of physical, mental, and functional problems. Therefore, cannabis use disorders (CUDs) may be a major public health concern. Given the adverse health consequences of CUDs, the present study seeks to find possible precursors of CUDs. The current study consisted of 5 waves of data collection from the Harlem Longitudinal Development Study. Among 816 participants, about half are African Americans (52%), and the other half are Puerto Ricans (48%). We used Mplus to obtain the triple trajectories of alcohol use, tobacco use, and depressive symptoms. Logistic regression analyses were then conducted to examine the associations between the trajectory groups and CUDs. The 5 trajectory groups were (1) moderate alcohol use, high tobacco use, and high depressive symptoms (MHH; 12%); (2) moderate alcohol use, high tobacco use, and low depressive symptoms (MHL; 26%); (3) moderate alcohol use, low tobacco use, and low depressive symptoms (MLL; 18%); (4) low alcohol use, no tobacco use, and high depressive symptoms (LNH; 11%); and (5) low alcohol use, no tobacco use, and low depressive symptoms (LNL; 33%). The MHH, MHL, MLL, and LNH trajectory groups were associated with an increased likelihood of having CUDs compared to the LNL trajectory group after controlling for a number of confounding factors (e.g., CUDs in the late 20s). The findings of the current longitudinal study suggest that treatments designed to reduce or quit drinking as well as smoking and to relieve depressive symptoms may reduce the prevalence of CUDs. (PsycINFO Database Record