Kevin T. Nead

International prevalence of indoor tanning: a systematic review and meta-analysis.

IMPORTANCE Indoor tanning is a known carcinogen, but the scope of exposure to this hazard is not known. OBJECTIVE To summarize the international prevalence of exposure to indoor tanning. DATA SOURCES Studies were identified through systematic searches of PubMed (1966 to present), Scopus (1823 to present), and Web of Science (1898 to present) databases, last performed on March 16, 2013. We also hand searched reference lists to identify records missed by database searches and publicly available data not yet published in the scientific literature. STUDY SELECTION Records reporting a prevalence of indoor tanning were eligible for inclusion. We excluded case-control studies, reports with insufficient study information, and reports of groups recruited using factors related to indoor tanning. Two independent investigators performed searches and study selection. Our search yielded 1976 unique records. After exclusions, 161 records were assessed for eligibility in full text, and 88 were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted data on characteristics of study participants, inclusion/exclusion criteria, data collection format, outcomes, and statistical methods. Random-effects meta-analyses were used to summarize the prevalence of indoor tanning in different age categories. We calculated the population proportional attributable risk of indoor tanning in the United States, Europe, and Australia for nonmelanoma skin cancer (NMSC) and melanoma. MAIN OUTCOMES AND MEASURES Ever and past-year exposure to indoor tanning. RESULTS The summary prevalence of ever exposure was 35.7% (95% CI, 27.5%-44.0%) for adults, 55.0% (33.0%-77.1%) for university students, and 19.3% (14.7%-24.0%) for adolescents. The summary prevalence of past-year exposure was 14.0% (95% CI, 11.5%-16.5%) for adults, 43.1% (21.7%-64.5%) for university students, and 18.3% (12.6%-24.0%) for adolescents. These results included data from 406 696 participants. The population proportional attributable risk were 3.0% to 21.8% for NMSC and 2.6% to 9.4% for melanoma, corresponding to more than 450 000 NMSC cases and more than 10 000 melanoma cases each year attributable to indoor tanning in the United States, Europe, and Australia. CONCLUSIONS AND RELEVANCE Exposure to indoor tanning is common in Western countries, especially among young persons. Given the large number of skin cancer cases attributable to indoor tanning, these findings highlight a major public health issue.

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Background and Aims Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches. Methods Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population. Results In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000. Conclusions Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

Platelet-Rich Plasma as a Treatment for Patellar Tendinopathy A Double-Blind, Randomized Controlled Trial

Background: Previous studies have shown improvement in patellar tendinopathy symptoms after platelet-rich plasma (PRP) injections, but no randomized controlled trial has compared PRP with dry needling (DN) for this condition. Purpose: To compare clinical outcomes in patellar tendinopathy after a single ultrasound-guided, leukocyte-rich PRP injection versus DN. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 23 patients with patellar tendinopathy on examination and MRI who had failed nonoperative treatment were enrolled and randomized to receive ultrasound-guided DN alone (DN group; n = 13) or with injection of leukocyte-rich PRP (PRP group; n = 10), along with standardized eccentric exercises. Patients and the physician providing follow-up care were blinded. Participants completed patient-reported outcome surveys before and at 3, 6, 9, 12, and ≥26 weeks after treatment during follow-up visits. The primary outcome measure was the Victorian Institute of Sports Assessment (VISA) score for patellar tendinopathy at 12 weeks, and secondary measures included the visual analog scale (VAS) for pain, Tegner activity scale, Lysholm knee scale, and Short Form (SF-12) questionnaire at 12 and ≥26 weeks. Results were analyzed using 2-tailed paired and unpaired t tests. Patients who were dissatisfied at 12 weeks were allowed to cross over into a separate unblinded arm. Results: At 12 weeks after treatment, VISA scores improved by a mean ± standard deviation of 5.2 ± 12.5 points (P = .20) in the DN group (n = 12) and by 25.4 ± 23.2 points (P = .01) in the PRP group (n = 9); at ≥26 weeks, the scores improved by 33.2 ± 14.0 points (P = .001) in the DN group (n = 9) and by 28.9 ± 25.2 points (P = .01) in the PRP group (n = 7). The PRP group had improved significantly more than the DN group at 12 weeks (P = .02), but the difference between groups was not significant at ≥26 weeks (P = .66). Lysholm scores were not significantly different between groups at 12 weeks (P = .81), but the DN group had improved significantly more than the PRP group at ≥26 weeks (P = .006). At 12 weeks, 3 patients in the DN group failed treatment and subsequently crossed over into the PRP group. These patients were excluded from the primary ≥26-week analysis. There were no treatment failures in the PRP group. No adverse events were reported. Recruitment was stopped because interim analysis demonstrated statistically significant and clinically important results. Conclusion: A therapeutic regimen of standardized eccentric exercise and ultrasound-guided leukocyte-rich PRP injection with DN accelerates the recovery from patellar tendinopathy relative to exercise and ultrasound-guided DN alone, but the apparent benefit of PRP dissipates over time.

Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk

PURPOSE To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimers disease risk. METHODS We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimers disease using 1:5 propensity score-matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimers disease risk. RESULTS There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score-matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimers disease risk. We also observed a statistically significant increased risk of Alzheimers disease with increasing duration of ADT (P = .016). CONCLUSION Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimers disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.

Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis

Background: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. Methods: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Results: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10-6). Conclusion: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk.

Exercise capacity is the strongest predictor of mortality in patients with peripheral arterial disease

OBJECTIVE The objective of this study was to assess the predictive value of clinical and exercise test variables in patients with peripheral arterial disease (PAD). METHODS A customized symptom-limited ramp treadmill protocol was used to assess 725 PAD patients referred for exercise testing at the Palo Alto Veterans Hospital between 1997 and 2011. Detailed clinical and exercise test data were collected at baseline, and patients were followed up for a mean of 11.3 ± 6.3 years. RESULTS During follow-up, there were 364 deaths. Baseline exercise capacity was 7.0 ± 2.6 metabolic equivalents (METs) among survivors and 5.5 ± 2.4 METs in those who died (P < .001). Although several physiologic parameters differed between survivors and nonsurvivors, age-adjusted Cox regression revealed that exercise capacity was the strongest independent predictor of death. Each additional MET achieved was associated with age-adjusted 18% and 20% reductions in all-cause and cardiovascular mortality, respectively (P < .001 for both). This variable surpassed all classical risk factors (including smoking and history of congestive heart failure) and all measured exercise test responses (including symptoms and electrocardiograph abnormalities). CONCLUSIONS Among PAD patients, reduced exercise capacity is the most powerful harbinger of long-term mortality. This factor has predictive power beyond traditional risk factors and confirms the critical importance of fitness in this cohort.

Association Between Androgen Deprivation Therapy and Risk of Dementia

Importance A growing body of evidence supports a link between androgen deprivation therapy (ADT) and cognitive dysfunction, including Alzheimer disease. However, it is currently unknown whether ADT may contribute to the risk of dementia more broadly. Objective To use an informatics approach to examine the association of ADT as a treatment for prostate cancer with the subsequent development of dementia (eg, senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia). Design, Setting, and Participants In this cohort study, a text-processing method was used to analyze electronic medical record data from an academic medical center from 1994 to 2013, with a median follow-up of 3.4 years (interquartile range, 1.0-7.2 years). We identified 9455 individuals with prostate cancer who were 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. We excluded 183 patients with a previous diagnosis of dementia. Our final cohort comprised 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT. Main Outcomes and Measures We tested the effect of ADT on the risk of dementia using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results Among 9272 men with prostate cancer (mean [SD] age, 66.9 [10.9] years; 5450 [58.8%] white), there was a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17; 95% CI, 1.58-2.99; P < .001). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32; 95% CI, 1.73-3.12; P < .001). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found that individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36; 95% CI, 1.64-3.38; P < .001). Kaplan-Meier analysis demonstrated that ADT users 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001). Conclusions and Relevance Androgen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.

Low lifetime recreational activity is a risk factor for peripheral arterial disease

BACKGROUND The relationship between lifetime physical activity and the risk of developing peripheral arterial disease (PAD) is not known. METHODS We studied 1381 patients referred for elective coronary angiography in a point prevalence analysis. PAD was defined as ankle-brachial index (ABI) <0.9 at the time or a history of revascularization of the lower extremities regardless of ABI measure. We used a validated physical activity questionnaire to retrospectively measure each patients lifetime recreational activity (LRA). Multivariate and logistic regression analyses were used to assess the independent association of LRA to ABI and the presence of PAD. RESULTS PAD was present in 19% (n = 258) of all subjects. Subjects reporting no regular LRA had greater diastolic blood pressure and were more likely to be female. They had lower average ABI, and a higher proportion had PAD (25.6%). In a regression model, including traditional risk factors and LRA, multivariate analysis showed that age (P < .001), female gender (P < .001), systolic blood pressure (P = .014), fasting glucose (P < .001), serum triglycerides (P = .02), and cumulative pack years (P < .001) were independent negative predictors of ABI, and LRA was a positive predictor of ABI (P < .001). History of sedentary lifestyle independently increased the odds ratio for PAD (odds ratio, 0.46; 95% confidence interval, 1.01-2.10) when assessed by logistic regression. Intriguingly, there is a correlation between physical activity and gender, such that women with low LRA are at greatest risk. CONCLUSION Recalled LRA is positively correlated to ABI and associated with PAD. Whereas the mechanism for this effect is not clear, LRA may be a useful clinical screening tool for PAD risk, and strategies to increase adult recreational activity may reduce the burden of PAD later in life.

Alternative ankle-brachial index method identifies additional at-risk individuals.

OBJECTIVES The aim of this study was to determine whether use of an alternative ankle-brachial index (ABI) calculation method improves mortality risk prediction compared with traditional methods. BACKGROUND The ABI is used to diagnose peripheral arterial disease (PAD) and to identify those at risk for cardiovascular events. Traditionally, the ABI is calculated with the higher of the dorsalis pedis and posterior tibial ankle arteries. Studies directly comparing calculation methods are limited. METHODS The ABI was calculated at baseline in 1,413 study participants undergoing non-emergent coronary angiography subsequently followed for all-cause and cardiovascular mortality. There were 224 individuals assigned to the traditional-PAD group (ABI <0.90) with the traditional ABI method. Of those remaining, an alternative ABI method using the lower of the 2 ankle pressures assigned 282 patients to the alternative-PAD group. The 862 individuals not assigned to PAD by either method were the no-PAD group. RESULTS There were 163 mortalities during a median follow-up of 5.0 years. Adjusted Cox regression models showed that the alternative-PAD group had an increased risk for all-cause (hazard ratio [HR]: 1.49; 95% confidence interval: 1.01 to 2.19) and cardiovascular mortality (HR: 3.21; 95% confidence interval: 1.53 to 6.37) versus the no-PAD group. Additionally, in the no-PAD group, there was an 11% (HR: 1.11; 95% confidence interval: 1.05 to 1.17) increased risk of all-cause mortality/1-mm Hg increased difference between the left and right brachial systolic pressures. CONCLUSIONS The implementation of an alternative ABI method and use of the brachial difference identifies individuals at an increased risk for mortality who are currently missed with traditional ABI methods. Current ABI protocols might need to be evaluated.

Proton pump inhibitors and vascular function: A prospective cross-over pilot study

Proton pump inhibitors (PPIs) are commonly used drugs for the treatment of gastric reflux. Recent retrospective cohorts and large database studies have raised concern that the use of PPIs is associated with increased cardiovascular (CV) risk. However, there is no prospective clinical study evaluating whether the use of PPIs directly causes CV harm. We conducted a controlled, open-label, cross-over pilot study among 21 adults aged 18 and older who are healthy (n=11) or have established clinical cardiovascular disease (n=10). Study subjects were assigned to receive a PPI (Prevacid; 30 mg) or a placebo pill once daily for 4 weeks. After a 2-week washout period, participants were crossed over to receive the alternate treatment for the ensuing 4 weeks. Subjects underwent evaluation of vascular function (by the EndoPAT technique) and had plasma levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of endothelial function previously implicated in PPI-mediated risk) measured prior to and after each treatment interval. We observed a marginal inverse correlation between the EndoPAT score and plasma levels of ADMA (r = −0.364). Subjects experienced a greater worsening in plasma ADMA levels while on PPI than on placebo, and this trend was more pronounced amongst those subjects with a history of vascular disease. However, these trends did not reach statistical significance, and PPI use was also not associated with an impairment in flow-mediated vasodilation during the course of this study. In conclusion, in this open-label, cross-over pilot study conducted among healthy subjects and coronary disease patients, PPI use did not significantly influence vascular endothelial function. Larger, long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes, which has recently been reported in retrospective cohort studies.