Nae Yuh Wang

Smoking, Smoking Cessation, and Risk for Type 2 Diabetes Mellitus: A Cohort Study

BACKGROUND Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown. OBJECTIVE To test the hypothesis that smoking cessation increases diabetes risk in the short term, possibly owing to cessation-related weight gain. DESIGN Prospective cohort study. SETTING The ARIC (Atherosclerosis Risk in Communities) Study. PATIENTS 10,892 middle-aged adults who initially did not have diabetes in 1987 to 1989. MEASUREMENTS Smoking was assessed by interview at baseline and at subsequent follow-up. Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004. RESULTS During 9 years of follow-up, 1254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years. LIMITATION Residual confounding is possible even with meticulous adjustment for established diabetes risk factors. CONCLUSION Cigarette smoking predicts incident type 2 diabetes, but smoking cessation leads to higher short-term risk. For smokers at risk for diabetes, smoking cessation should be coupled with strategies for diabetes prevention and early detection.

The acceptability of treatment for depression among African-American, hispanic, and white primary care patients

Background. Ethnic minority patients are less likely than white patients to receive guideline-concordant care for depression. It is uncertain whether racial and ethnic differences exist in patient beliefs, attitudes, and preferences for treatment. Methods. A telephone survey was conducted of 829 adult patients (659 non-Hispanic whites, 97 African Americans, 73 Hispanics) recruited from primary care offices across the United States who reported 1 week or more of depressed mood or loss of interest within the past month and who met criteria for Major Depressive Episode in the past year. Within this cohort, we examined differences among African Americans, Hispanics, and whites in acceptability of antidepressant medication and acceptability of individual counseling. Results. African Americans (adjusted OR, 0.30; 95% CI 0.19–0.48) and Hispanics (adjusted OR, 0.44; 95% CI, 0.26–0.76) had lower odds than white persons of finding antidepressant medications acceptable. African Americans had somewhat lower odds (adjusted OR, 0.63; 95% CI, 0.35–1.12), and Hispanics had higher odds (adjusted OR, 3.26; 95% CI, 1.08–9.89) of finding counseling acceptable than white persons. Some negative beliefs regarding treatment were more prevalent among ethnic minorities; however adjustment for these beliefs did not explain differences in acceptability of treatment for depression. Conclusions. African Americans are less likely than white persons to find antidepressant medication acceptable. Hispanics are less likely to find antidepressant medication acceptable, and more likely to find counseling acceptable than white persons. Racial and ethnic differences in beliefs about treatment modalities were found, but did not explain differences in the acceptability of depression treatment. Clinicians should consider patients’ cultural and social context when negotiating treatment decisions for depression. Future research should identify other attitudinal barriers to depression care among ethnic minority patients.

Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis

Osteoarthritis is a major contributor to functional impairment and reduced independence in older adults (1-4). It is the leading cause of arthritis in the United States, affecting an estimated 21 million persons (5), and has substantial economic impact (6, 7). History of an injury to a joint, particularly at the knee and hip, is associated with an increased risk for osteoarthritis in cross-sectional and casecontrol studies (8-11). Such studies, however, may overestimate this relation because persons with symptomatic osteoarthritis may be more likely to recall a past injury or to interpret early symptoms of osteoarthritis as indicative of joint injury. A prospective cohort study can address this weakness by determining exposure status before the outcome develops. To date, prospective studies have examined the relation between history of joint injury and osteoarthritis in middle-aged persons and senior citizens (12, 13), but not in young adults. However, many athletic injuries occur in high school and college. In addition, joint trauma may be a more common cause of osteoarthritis than has been previously recognized (14). We performed a prospective cohort study of 1321 young adults to examine the risk for knee and hip osteoarthritis associated with joint injury during young adult life. Methods Study Participants The Johns Hopkins Precursors Study was designed by the late Caroline Bedell Thomas, MD, to identify precursors of the aging process (15). A total of 1337 medical students, members of the graduating classes of 1948 through 1964 at the Johns Hopkins University School of Medicine in Baltimore, Maryland, enrolled in the study. The cohort was 91% male and 97% white; the mean age was 22 years. At entry, participants underwent a standard history and examination, including assessment of musculoskeletal disorders, history of trauma, level of physical activity, and measurement of weight and height. Body mass index was calculated as weight in kilograms divided by height in meters squared. In addition, participants were asked to categorize their level of physical training during the past month as none, little, moderate, or much, as described elsewhere (16). Since graduation, participants have been followed prospectively with annual self-administered questionnaires to detect incident disease and to update risk factor status over time. At the time that baseline data were collected, it was not customary to obtain informed consent. After establishment of the Joint Committee on Clinical Investigation at Johns Hopkins, the follow-up protocol was reviewed and approved. Assessment of Injury Injury was defined as a report of trauma to the knee or hip joint, including internal derangement and fracture. During the baseline assessment, knee and hip injuries that occurred before graduation from medical school and the year of their occurrence were recorded. Postgraduation injuries were assessed by annual morbidity questionnaires. During every 5-year follow-up period, at least 86% of the living participants responded at least once to the questionnaires. Injuries were assigned diagnosis codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) (17). Diagnoses included torn meniscus (code 836.2); torn knee ligament (code 844.9); tibial fracture (code 823.8); femoral fracture (code 821.01); fibular fracture (code 823.81); patellar fracture (code 822); broken leg, site not otherwise specified (code 827.0); knee injury, not otherwise specified (code 959.7); gunshot wound (code 891); hemarthrosis (code 844.9); shin splints (code 844.9); and hip dislocation (code 836.5). Incidence of Osteoarthritis The methods used to determine osteoarthritis incidence in this cohort have been described elsewhere (18). Briefly, all participants were mailed annual morbidity questionnaires. Before 1985, respondents were queried about the development of physical and musculoskeletal disorders. Since 1985, follow-up morbidity questionnaires have contained the specific question, Have you ever had arthritis? and have asked those who respond affirmatively to provide the type of arthritis, year of onset, and treatment received. An event of osteoarthritis was defined as the self-report of osteoarthritis or degenerative arthritis in response to the questionnaire. The incidence date was determined by the reported year of osteoarthritis onset. Two rheumatologists reviewed each report of osteoarthritis, assigned ICD-9-CM codes (17) to the most specific arthritis site reported by the respondent, and excluded inflammatory arthritides. For this analysis, only osteoarthritis at the knee (code 715.96) and hip (code 715.95) were included as outcomes. In 1995, all surviving participants who had previously reported osteoarthritis were mailed a more detailed questionnaire. They were asked, Have you had pain in or around the knee, including back of the knee, on most days for at least 1 month? and Have you had pain in or around either hip joint, including the buttock, groin, and side of upper thigh, on most days for at least 1 month? These symptom-related questions were used to screen for knee and hip osteoarthritis, respectively, in the National Health and Nutrition Examination Survey (NHANES) (19). Respondents were also asked whether they had undergone radiographic evaluation of their knees and hips and whether radiography revealed osteophytes, joint space narrowing, subchondral cysts, or bony sclerosis (the radiographic hallmarks of osteoarthritis) (20). Statistical Analysis The association between baseline characteristics and injury status was assessed by using the Student t-test for continuous variables and the chi-square test for categorical variables. These data are presented both for the entire cohort and separately by sex. Injury was the independent variable in the survival analysis; age was the time variable. Knee and hip osteoarthritis were examined as separate outcomes. The relation of a joint injury at baseline to the incidence of osteoarthritis was examined by using KaplanMeier analysis (21). The log-rank statistic was used to test whether the cumulative incidence of osteoarthritis differed according to injury status at cohort entry (22). In addition, Cox proportional-hazards analysis was used to estimate the independent risk for osteoarthritis associated with a joint injury. Cox models were constructed for injury status at cohort entry and over follow-up, modeled as a time-dependent covariate. We adjusted for age at graduation, sex, body mass index, and level of physical activity, each of which was determined at baseline, to evaluate for possible confounding. In this cohort, body mass index at enrollment was more predictive of future osteoarthritis than average or most recent body mass index during follow-up (18). These analyses were performed for all reported events of knee and hip osteoarthritis and for cases confirmed by both characteristic symptoms and radiographic findings. Hazard ratios are reported as relative risks with 95% CIs. Statistical significance was defined as an level equal to 0.05 using a two-tailed test. We conducted a sensitivity analysis to assess the potential effect of an omitted covariate on the association between joint injury and subsequent osteoarthritis. Role of the Funding Sources The funding sources did not have a role in the collection, analysis, or interpretation of the data or in the decision to submit the study for publication. Results At graduation from medical school, the average age of the 1216 men and 121 women in the cohort was 26 years. Our analysis is based on events reported through 30 November 1995 and represents a median follow-up of 36 years. Information at baseline or during follow-up was available for 1321 participants, who form the basis of our longitudinal analysis. At the end of follow-up in 1995, the mean age of the cohort SD was 61.4 8.9 years. Overall, 141 participants had a joint injury (knee alone [n =111], hip alone [n =16], or injuries at both sites [n =14]) before or after graduation. Table 1 shows the baseline characteristics of the cohort according to injury status at the end of follow-up. Proportions of men and women with joint injury were similar (P >0.2, chi-square test). Participants were generally lean, 49% were physically active, and 54% smoked cigarettes. Men who had a joint injury were heavier at baseline than men who were injury-free, but both groups of men were similar in age, level of physical activity, and smoking status. Women with injury were, on average, 2 years older at baseline than those without injury. Table 1. Baseline Characteristics of 1321 Men and Women according to Joint Injury at Cohort Entry or during Follow-up At baseline, 47 men (3.9%) reported a knee injury and 12 men (1.0%) reported a hip injury. The mean age at which the injuries occurred was 16 years. Knee injuries included 10 tibial fractures, 3 fibular fractures, 4 femoral fractures, 2 patellar fractures, and 9 otherwise unspecified leg fractures. In addition, 8 men incurred trauma resulting in torn knee cartilage, 2 had torn knee ligaments, 2 had knee injuries resulting from gunshot wounds, 1 had traumatic hemarthrosis, 1 had joint dislocation, 1 had shin splints, and 4 had otherwise unspecified knee injuries. Of men with a knee injury, 4 reported that they were injured while playing football, 2 each reported that they were injured while playing basketball or participating in athletics, and 1 each reported that he was injured while horseback riding, bicycling, skiing, playing volleyball, wrestling, playing baseball, or playing tennis. Knee trauma also resulted from motor vehicle accidents (n =3) and falls (n =2). At baseline, 4 of the 121 women (3.3%) had a history of knee injuries and 1 (0.8%) had a history of hip injuries. Sixty-two men and 7 women developed knee osteoarthritis, and 27 men and 5 women developed hip osteoarthritis. The mean SD ages at onset of knee

Spoken Language Development in Children Following Cochlear Implantation

CONTEXT Cochlear implantation is a surgical alternative to traditional amplification (hearing aids) that can facilitate spoken language development in young children with severe to profound sensorineural hearing loss (SNHL). OBJECTIVE To prospectively assess spoken language acquisition following cochlear implantation in young children. DESIGN, SETTING, AND PARTICIPANTS Prospective, longitudinal, and multidimensional assessment of spoken language development over a 3-year period in children who underwent cochlear implantation before 5 years of age (n = 188) from 6 US centers and hearing children of similar ages (n = 97) from 2 preschools recruited between November 2002 and December 2004. Follow-up completed between November 2005 and May 2008. MAIN OUTCOME MEASURES Performance on measures of spoken language comprehension and expression (Reynell Developmental Language Scales). RESULTS Children undergoing cochlear implantation showed greater improvement in spoken language performance (10.4; 95% confidence interval [CI], 9.6-11.2 points per year in comprehension; 8.4; 95% CI, 7.8-9.0 in expression) than would be predicted by their preimplantation baseline scores (5.4; 95% CI, 4.1-6.7, comprehension; 5.8; 95% CI, 4.6-7.0, expression), although mean scores were not restored to age-appropriate levels after 3 years. Younger age at cochlear implantation was associated with significantly steeper rate increases in comprehension (1.1; 95% CI, 0.5-1.7 points per year younger) and expression (1.0; 95% CI, 0.6-1.5 points per year younger). Similarly, each 1-year shorter history of hearing deficit was associated with steeper rate increases in comprehension (0.8; 95% CI, 0.2-1.2 points per year shorter) and expression (0.6; 95% CI, 0.2-1.0 points per year shorter). In multivariable analyses, greater residual hearing prior to cochlear implantation, higher ratings of parent-child interactions, and higher socioeconomic status were associated with greater rates of improvement in comprehension and expression. CONCLUSION The use of cochlear implants in young children was associated with better spoken language learning than would be predicted from their preimplantation scores.

Comparative Effectiveness of Weight-Loss Interventions in Clinical Practice

BACKGROUND Obesity and its cardiovascular complications are extremely common medical problems, but evidence on how to accomplish weight loss in clinical practice is sparse. METHODS We conducted a randomized, controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor. Participants were recruited from six primary care practices; 63.6% were women, 41.0% were black, and the mean age was 54.0 years. One intervention provided patients with weight-loss support remotely--through the telephone, a study-specific Web site, and e-mail. The other intervention provided in-person support during group and individual sessions, along with the three remote means of support. There was also a control group in which weight loss was self-directed. Outcomes were compared between each intervention group and the control group and between the two intervention groups. For both interventions, primary care providers reinforced participation at routinely scheduled visits. The trial duration was 24 months. RESULTS At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) for all participants was 36.6, and the mean weight was 103.8 kg. At 24 months, the mean change in weight from baseline was -0.8 kg in the control group, -4.6 kg in the group receiving remote support only (P<0.001 for the comparison with the control group), and -5.1 kg in the group receiving in-person support (P<0.001 for the comparison with the control group). The percentage of participants who lost 5% or more of their initial weight was 18.8% in the control group, 38.2% in the group receiving remote support only, and 41.4% in the group receiving in-person support. The change in weight from baseline did not differ significantly between the two intervention groups. CONCLUSIONS In two behavioral interventions, one delivered with in-person support and the other delivered remotely, without face-to-face contact between participants and weight-loss coaches, obese patients achieved and sustained clinically significant weight loss over a period of 24 months. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00783315.).

A Behavioral Weight-Loss Intervention in Persons with Serious Mental Illness

BACKGROUND Overweight and obesity are epidemic among persons with serious mental illness, yet weight-loss trials systematically exclude this vulnerable population. Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent. Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness. METHODS We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and randomly assigned them to an intervention or a control group. Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions. Weight change was assessed at 6, 12, and 18 months. RESULTS Of 291 participants who underwent randomization, 58.1% had schizophrenia or a schizoaffective disorder, 22.0% had bipolar disorder, and 12.0% had major depression. At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.3, and the mean weight was 102.7 kg (225.9 lb). Data on weight at 18 months were obtained from 279 participants. Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit. At 18 months, the mean between-group difference in weight (change in intervention group minus change in control group) was -3.2 kg (-7.0 lb, P=0.002); 37.8% of the participants in the intervention group lost 5% or more of their initial weight, as compared with 22.7% of those in the control group (P=0.009). There were no significant between-group differences in adverse events. CONCLUSIONS A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness. Given the epidemic of obesity and weight-related disease among persons with serious mental illness, our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population. (Funded by the National Institute of Mental Health; ACHIEVE ClinicalTrials.gov number, NCT00902694.).

Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion

Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, GNB3 (G protein β3 subunit) 825T, account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate.

Lifestyle Interventions Reduce Coronary Heart Disease Risk: Results From the PREMIER Trial

Background— Although trials of lifestyle interventions generally focus on cardiovascular disease risk factors rather than hard clinical outcomes, 10-year coronary heart disease (CHD) risk can be estimated from the Framingham risk equations. Our objectives were to study the effect of 2 multicomponent lifestyle interventions on estimated CHD risk relative to advice alone and to evaluate whether differences can be observed in the effects of the lifestyle interventions among subgroups defined by baseline variables. Methods and Results— A total of 810 healthy adults with untreated prehypertension or stage I hypertension were randomized to 1 of 3 intervention groups: An “advice-only” group, an “established” group that used established lifestyle recommendations for blood pressure control (sodium reduction, weight loss, and increased physical activity), or an “established-plus-DASH” group that combined established lifestyle recommendations with the DASH (Dietary Approaches to Stop Hypertension) diet. The primary outcome was 10-year CHD risk, estimated from follow-up data collected at 6 months. A secondary outcome was 10-year CHD risk at 18 months. Of the 810 participants, 62% were women and 34% were black. Mean age was 50 years, mean systolic/diastolic blood pressure was 135/85 mm Hg, and median baseline Framingham risk was 1.9%. The relative risk ratio comparing 6-month to baseline Framingham risk was 0.86 (95% confidence interval 0.81 to 0.91, P<0.001) in the established group and 0.88 (95% confidence interval 0.83 to 0.94, P<0.001) in the established-plus-DASH group relative to advice alone. Results were virtually identical in sensitivity analyses, in each major subgroup, and at 18 months. Conclusions— The observed reductions of 12% to 14% in estimated CHD risk are substantial and, if achieved, should have important public health benefits.

Cross-Sectional and Prospective Study of Lung Function in Adults With Type 2 Diabetes The Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVE—The aim of this study was to test the hypothesis that diabetes is independently associated with reduced lung function, both cross-sectionally and longitudinally. RESEARCH DESIGN AND METHODS—We conducted cross-sectional and prospective analyses of diabetes status and lung function decline using baseline and 3-year follow-up data on 1,100 diabetic and 10,162 nondiabetic middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) Study. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at baseline and at the 3-year follow-up using standard spirometry. RESULTS—At baseline, adults with diabetes had significantly lower predicted FVC (96 vs. 103%, P < 0.001) and predicted FEV1 (92 vs. 96%, P < 0.001) than those without diabetes. These differences remained significant after adjustment for demographic characteristics, adiposity, smoking, physical activity index, education, and ARIC field center. Graded, inverse associations were observed between hyperglycemia, diabetes severity (i.e., duration of diabetes and types of antidiabetes medications), and FVC and FEV1 (all Ptrend < 0.001). In prospective analyses, FVC declined faster in diabetic adults than in their nondiabetic counterparts (64 vs. 58 ml/year, P = 0.01). Diabetes severity as indicated by intensity of antidiabetic treatment also showed graded relationships with the rate of FVC decline (P < 0.01). CONCLUSIONS—These data support the notion that the lung is a target organ for diabetic injury. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance.

Primary Care Patients' Involvement in Decision-Making Is Associated with Improvement in Depression

Background:Depression is undertreated in primary care settings. Little research investigates the impact of patient involvement in decisions on guideline-concordant treatment and depression outcomes. Objective:The objective of this study was to determine whether patient involvement in decision-making is associated with guideline-concordant care and improvement in depression symptoms. Design:Prospective cohort study. Setting:Multisite, nationwide randomized clinical trial of quality improvement strategies for depression in primary care. Subjects:Primary care patients with current symptoms and probable depressive disorder. Measurements:Patients rated their involvement in decision-making (IDM) about their care on a 5-point scale from poor to excellent 6 months after entry into the study. Depressive symptoms were measured every 6 months for 2 years using a modified version of theCenter for Epidemiologic Studies–Depression (CES-D) scale. We examined probabilities (Pr) of receipt of guideline-concordant care and resolution of depression across IDM groups using multivariate logistic regression models controlling for patient and provider factors. Results:For each 1-point increase in IDM ratings, the probability of patients’ report of receiving guideline-concordant care increased 4% to 5% (adjusted Pr 0.31 vs. 0.50 for the lowest and highest IDM ratings, respectively, P < 0.001). Similarly, for each 1-point increase in IDM ratings, the probability of depression resolution increased 2% to 3% (adjusted Pr 0.10 vs. 0.19 for the lowest and highest IDM ratings respectively, P = 0.004). Conclusions:Depressed patients with higher ratings of involvement in medical decisions have a higher probability of receiving guideline-concordant care and improving their symptoms over an 18-month period. Interventions to increase patient involvement in decision-making may be an important means of improving care for and outcomes of depression.