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Importance Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice. Objective To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD. Design, Setting, and Participants Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year. Exposures Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (

Importance Diabetic macular edema (DME) is a leading cause of vision loss in persons with diabetes mellitus. Although there are national estimates for the prevalence of diabetic retinopathy and its risk factors among persons with diabetes, to our knowledge, no comparable estimates are available for DME specifically. Objectives To estimate the prevalence of DME in the US population and to identify associated risk factors. Design, Setting, and Participants A cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and valid fundus photographs in the 2005 to 2008 National Health and Nutrition Examination Survey. Main Outcomes and Measures The overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex. Results Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746 000 persons in the US 2010 population aged 40 years or older. We identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis showed that the odds of having DME were higher for non-Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19-5.84; P = .02). Elevated levels of glycosylated hemoglobin A 1c (OR, 1.47; 95% CI, 1.26-1.71 for each 1%; P P Conclusions and Relevance These results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A 1c , and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation is even more important for those at higher risk for DME.

Importance Thickening of the center of the retina, diabetic macular edema (DME), is the most common cause of visual loss due to diabetes mellitus. Treatment of DME has improved dramatically, and the prompt diagnosis of DME and referral of these patients have become more critical. Nonetheless, awareness of and care for DME in the US population is uncharacterized. Objective To characterize eye care and awareness of eye disease among persons with DME in the general US population. Design, Setting, and Participants Cross-sectional analysis of data from participants in the 2005 to 2008 National Health and Nutrition Examination Survey 40 years or older with diabetes mellitus and fundus photographs. Main Outcomes and Measures Among persons with DME, (1) awareness that diabetes has affected their eyes; (2) report on the last time they visited a diabetes specialist; (3) report on their last eye examination with pupil dilation; and (4) prevalence of visual impairment. Results In 2010, only 44.7% (95% CI, 27.0%-62.4%) of US adults 40 years or older with DME reported being told by a physician that diabetes had affected their eyes or that they had retinopathy; 46.7% (95% CI, 27.5%-66.0%), that they had visited a diabetes nurse educator, dietician, or nutritionist for their diabetes mellitus more than 1 year ago or never; and 59.7% (95% CI, 43.5%-75.9%), that they had received an eye examination with pupil dilation in the last year. Among persons with DME, 28.7% (95% CI, 12.7%-44.7%) were visually impaired (defined as visual acuity worse than 20/40 in the eye with DME) based on visual acuity at the initial examination and 16.0% (95% CI, 2.5%-29.4%) based on best-corrected visual acuity. Conclusions and Relevance Many persons with diabetes mellitus in the United States are not getting care that can prevent visual impairment and blindness. Strategies to increase awareness are warranted, especially given the recent availability of improved therapies for DME.

ContextPrevious studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system.ObjectiveTo determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication.Design, Setting, and ParticipantsA total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study.Main Outcome MeasuresIncident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism.ResultsIndividuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease.ConclusionOur data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.

In Reply. —Dr Helfand points out that it is not possible to know in advance which symptomatic patients with mild thyroid failure will respond to thyroxine sodium therapy. He questions the precise benefit achieved from symptom relief in our decision and cost-effectiveness analysis and the impact that uncertainty regarding the reversibility of symptoms has on the final results. We have considered this issue further and find that it has little effect on the results of the model for 3 reasons. First, relatively few patients were treated for potentially reversible symptoms alone. Because there are no data regarding overlap of the 3 treatment indications—reversible symptoms (28% of patients), antithyroid antibodies predicting progression of disease (67% of women, 40% of men), and hypercholesterolemia (25% of patients)—we assumed that these treatment indications were independently associated in patients with mild thyroid failure. Consequently, most patients with symptoms also had another indication for treatment; only 6% of

To the Editor. —In their analysis of thyroid screening, Mr Danese and colleagues 1 point out that most of the net benefit comes from minimizing the sequelae of mild thyroid failure and clinically overt hypothyroidism. Since these conditions are rarely fatal, the value of thyroid screening is thus largely attributable to quality-of-life improvements. In a Markov model (as used by the authors), the quality-of-life effect of an adverse clinical condition is a function of the quality-adjustment factor (utility) and the time patients spend in the state. Thirty percent of the net benefit of thyroid screening (for women) was the result of reducing the symptoms associated with the health state "mild thyroid failure"—patients with an elevated thyrotropin (TSH), but no sign of overt hypothyroidism. This state was given a utility of 0.90, similar to that assigned to patients with severe back pain, ulcer disease, or angina. The authors either have assigned

Objective. —To estimate the cost-effectiveness of periodic screening for mild thyroid failure by measurement of serum thyroid stimulating hormone (TSH) concentration. Design. —Cost-utility analysis using a state-transition computer decision model that accounted for case finding, medical consequences of mild thyroid failure, and costs of care during 40 years of simulated follow-up. Setting. —Periodic health examinations in offices of primary care physicians. Patients. —Hypothetical cohorts of women and men screened every 5 years during the recommended periodic examination, beginning at age 35 years. Interventions. —Adding the serum TSH assay to total serum cholesterol screening was compared to cholesterol screening alone. Main Outcome Measures. —Discounted quality-adjusted life years (QALYs) and direct medical costs from a societal perspective. Results. —The cost-effectiveness of screening 35-year-old patients with a serum TSH assay every 5 years was $9223 per QALY for women and $22 595 per QALY for men. The cost-effectiveness became more favorable when age at first screening was increased for both sexes and was always more favorable for women than men. Reduced progression to overt hypothyroidism and relief of symptoms increased QALYs, but did not substantially reduce direct medical costs. Finding hypercholesterolemia induced by mild thyroid failure reduced direct medical costs, but did not substantially increase QALYs. The cost of a TSH assay and the importance to patients of symptoms associated with thyroid failure were the most influential factors in sensitivity analyses. Conclusions. —The cost-effectiveness of screening for mild thyroid failure compares favorably with other generally accepted preventive medical practices. Physicians should consider measuring serum TSH concentration in patients aged 35 years and older undergoing routine periodic health examinations. The costeffectiveness of screening is most favorable in elderly women.