Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions.

Importance: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated. Objective: To assess the association between consumption of common caffeinated products and the risk of arrhythmias. Design, Setting, and Participants: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses. Exposures: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism. Main Outcomes and Measures: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. Results: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia. Conclusions and Relevance: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

Recovery of Iron Stores After Adolescents Donate Blood.

BACKGROUND: Teenagers aged 16 to 18 are at increased risk for iron deficiency, exacerbated by losses with whole blood (WB) or double red blood cell (2RBC) donations. Required 56-day (WB) or 112-day (2RBC) interdonation intervals (IDIs) are too short for many to replace lost iron without supplements. METHODS: Teenagers donating WB or 2RBCs at Vitalant, a national blood provider, had serum ferritin measured at their first and immediately subsequent successful donation from December 2016 to 2018. We modeled postindex log-ferritin as a function of IDI to estimate the shortest intervals that corresponded with 50% to 95% prevalence of adequate donor iron stores (ferritin ≥20 ng/mL female donors, ≥30 ng/mL male donors) at the subsequent donation. RESULTS: Among 30 806 teenagers, 11.4% of female and 9.7% of male donors had inadequate iron stores at index donation. Overall, 92.6% had follow-up ferritin values within 13 months. Approximately 12 months after WB index donations, >60% of female and >80% of male donors had adequate iron stores (>50% and >70% after 2RBC donations). Follow-up-donation iron stores were highly dependent on index ferritin. Less than half of WB donors with low ferritin at index achieved adequate stores within 12 months. Achieving a ≥90% prevalence of adequate ferritin at 12 months required index values >50 ng/mL. CONCLUSIONS: These findings suggest that postdonation low-dose iron supplements should be strongly encouraged in teenagers with borderline or low iron stores to permit donation without increased risk for symptoms of mild iron depletion. Increasing the minimum recommended IDI to allow time for replacing donation-related iron losses may be desirable for teenagers.

Quarterly screening optimizes detection of sexually transmitted infections when prescribing HIV preexposure prophylaxis.

OBJECTIVE: The optimal screening frequency of sexually transmitted infections (STIs) for MSM and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with present guidelines recommending screening every 3-6 months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. DESIGN: The US PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami, and a community health center in Washington, DC. In all, 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. METHODS: The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every 6 versus every 3 months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. RESULTS: Among the participants, 50.9% had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to 3 months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. CONCLUSIONS: Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs, and decrease transmission.

Comorbid Diabetes and Severe Mental Illness: Outcomes in an Integrated Health Care Delivery System.

BACKGROUND: Diabetes prevalence is twice as high among people with severe mental illness (SMI) when compared to the general population. Despite high prevalence, care outcomes are not well understood. OBJECTIVE: To compare diabetes health outcomes received by people with and without comorbid SMI, and to understand demographic factors associated with poor diabetes control among those with SMI. DESIGN: Retrospective cohort study PARTICIPANTS: 269,243 adults with diabetes MAIN MEASURES: Primary outcomes included optimal glycemic control (A1c < 7) or poor diabetes control (A1c > 9) in 2014. Secondary outcomes included control of other cardiometabolic risk factors (hypertension, dyslipidemia, smoking) and recommended diabetes monitoring. KEY RESULTS: Among this cohort, people with SMI (N = 4,399), compared to those without SMI (N = 264,844), were more likely to have optimal glycemic control, adjusting for various covariates (adjusted relative risk (aRR) 1.25, 95% CI 1.21-1.28, p < .001) and less likely to have poor control (aRR 0.92, 95% CI 0.87-0.98, p = 0.012). Better blood pressure and lipid control was more prevalent among people with SMI when compared to those without SMI (aRR 1.03; 95% CI 1.02-1.05, p < .001; aRR 1.02; 95% CI 1.00-1.05, p = 0.044, respectively). No differences were observed in recommended A1c or LDL testing, but people with SMI were more likely to have blood pressure checked (aRR 1.02, 95% CI 1.02-1.03, p < .001) and less likely to receive retinopathy screening (aRR 0.80, 95% CI 0.71-0.91, p < .001) than those without SMI. Among people with diabetes and comorbid SMI, younger adults and Hispanics were more likely to have poor diabetes control. CONCLUSIONS: Adults with diabetes and comorbid SMI had better cardiometabolic control than people with diabetes who did not have SMI, despite lower rates of retinopathy screening. Among those with comorbid SMI, younger adults and Hispanics were more vulnerable to poor A1c control.

Acupressure to Reduce Treatment-Related Symptoms for Children With Cancer and Recipients of Hematopoietic Stem Cell Transplant: Protocol for a Randomized Controlled Trial.

BACKGROUND: We describe the study design and protocol of a pragmatic randomized controlled trial (RCT) Acupressure for Children in Treatment for a Childhood Cancer (ACT-CC). OBJECTIVE: To describe the feasibility and effectiveness of an acupressure intervention to decrease treatment-related symptoms in children in treatment for cancer or recipients of a chemotherapy-based hematopoietic stem cell transplant (HSCT). DESIGN: Two-armed RCTs with enrollment of 5 to 30 study days. SETTING: Two pediatric teaching hospitals. PATIENTS: Eighty-five children receiving cancer treatment or a chemotherapy-based HSCT each with 1 parent or caregiver. INTERVENTION: Patients are randomized 1:1 to receive either usual care plus daily professional acupressure and caregiver delivered acupressure versus usual care alone for symptom management. Participants receive up to 20 professional treatments. MAIN OUTCOME: A composite nausea/vomiting measure for the child. SECONDARY OUTCOMES: Child's nausea, vomiting, pain, fatigue, depression, anxiety, and positive affect. PARENT OUTCOMES: Depression, anxiety, posttraumatic stress symptoms, caregiver self-efficacy, and positive affect. Feasibility of delivering the semistandardized intervention will be described. Linear mixed models will be used to compare outcomes between arms in children and parents, allowing for variability in diagnosis, treatment, and age. DISCUSSION: Trial results could help childhood cancer and HSCT treatment centers decide about the regular inclusion of trained acupressure providers to support symptom management.

A group-based yoga program for urinary incontinence in ambulatory women: feasibility, tolerability, and change in incontinence frequency over 3 months in a single-center randomized trial.

BACKGROUND: Because of the limitations of existing clinical treatments for urinary incontinence, many women with incontinence are interested in complementary strategies for managing their symptoms. Yoga has been recommended as a behavioral self-management strategy for incontinence, but evidence of its feasibility, tolerability, and efficacy is lacking. OBJECTIVE: To evaluate the feasibility and tolerability of a group-based therapeutic yoga program for ambulatory middle-aged and older women with incontinence, and to examine preliminary changes in incontinence frequency as the primary efficacy outcome after 3 months. MATERIALS AND METHODS: Ambulatory women aged 50 years or older who reported at least daily stress-, urgency-, or mixed-type incontinence, were not already engaged in yoga, and were willing to temporarily forgo clinical incontinence treatments were recruited into a randomized trial in the San Francisco Bay area. Women were randomly assigned to take part in a program of twice-weekly group classes and once-weekly home practice focused on Iyengar-based yoga techniques selected by an expert yoga panel (yoga group), or a nonspecific muscle stretching and strengthening program designed to provide a rigorous time-and-attention control (control group) for 3 months. All participants also received written, evidence-based information about behavioral incontinence self-management techniques (pelvic floor exercises, bladder training) consistent with usual first-line care. Incontinence frequency and type were assessed by validated voiding diaries. Analysis of covariance models examined within- and between-group changes in incontinence frequency as the primary efficacy outcome over 3 months. RESULTS: Of the 56 women randomized (28 to yoga, 28 to control), the mean age was 65.4 (±8.1) years (range, 55-83 years), the mean baseline incontinence frequency was 3.5 (±2.0) episodes/d, and 37 women (66%) had urgency-predominant incontinence. A total of 50 women completed their assigned 3-month intervention program (89%), including 27 in the yoga and 23 in the control group (P = .19). Of those, 24 (89%) in the yoga and 20 (87%) in the control group attended at least 80% of group classes. Over 3 months, total incontinence frequency decreased by an average of 76% from baseline in the yoga and 56% in the control group (P = .07 for between-group difference). Stress incontinence frequency also decreased by an average of 61% in the yoga group and 35% in controls (P = .045 for between-group difference), but changes in urgency incontinence frequency did not differ significantly between groups. A total of 48 nonserious adverse events were reported, including 23 in the yoga and 25 in the control group, but none were directly attributable to yoga or control program practice. CONCLUSION: Findings demonstrate the feasibility of recruiting and retaining incontinent women across the aging spectrum into a therapeutic yoga program, and provide preliminary evidence of reduction in total and stress-type incontinence frequency after 3 months of yoga practice. When taught with attention to women's clinical needs, yoga may offer a potential community-based behavioral self-management strategy for incontinence to enhance clinical treatment, although future research should assess whether yoga offers unique benefits for incontinence above and beyond other physical activity-based interventions.

Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months.

Diabetes Screening among Antipsychotic-Treated Adults with Severe Mental Illness in an Integrated Delivery System: A Retrospective Cohort Study.

BACKGROUND: Severe mental illness (SMI) is associated with increased risk for type 2 diabetes, partly due to adverse metabolic effects of antipsychotic medications. In public health care settings, annual screening rates are 30%. We measured adherence to national diabetes screening guidelines for patients taking antipsychotic medications. OBJECTIVE: To estimate diabetes screening prevalence among patients with SMI within an integrated health care system, and to assess characteristics associated with lack of screening. DESIGN: Retrospective cohort study. PARTICIPANTS: Antipsychotic-treated adults with SMI. We excluded participants with known diabetes. MAIN MEASURES: Primary outcome was screening via fasting glucose test or hemoglobin A1c during a 1-year period. KEY RESULTS: In 2014, 16,754 patients with SMI diagnoses were receiving antipsychotics. Seventy-four percent of these patients' providers ordered diabetes screening tests that year, but only 55% (9247/16,754) received screening. When the observation time frame was extended to 2 years, 73% (12,250/16,754) were screened. Adjusting for sex and race/ethnicity, young adults (aged 18-29 years) were less likely to receive screening than older age groups [adjusted RR (aRR) 1.23-1.57, p < 0.0001]. Compared to whites, screening was more common for Asians (aRR 1.141, 95% CI 1.089-1.195, p < 0.0001), less common for blacks (aRR 0.946, 95% CI 0.898-0.997, p < 0.0375), and no different for Hispanics (aRR 1.030, 95% CI 0.988-1.074, p = 0.165). Smokers were less likely to be screened than non-smokers (aRR 0.93, 95% CI 0.89-0.97, p < 0.0008). Utilization of either mental health or primary care services increased the likelihood of screening. CONCLUSIONS: While almost three-fourths of adults with SMI taking antipsychotic medications received a lab order for diabetes screening, only 55% received screening within a 12-month period. Young adults and smokers were less likely to be screened, despite their disproportionate metabolic risk. Future studies should assess the barriers and facilitators with regard to diabetes screening in this vulnerable population at the patient, provider, and system levels.

Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis.

BACKGROUND: The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. METHODS: Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. RESULTS: Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) % predicted were declining at a mean rate of 0.12% (P < .001) and 0.10% (P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% (P = .103) and Dlco increased by 3.9% (P < .001). CONCLUSIONS: Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.

Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia.

Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 µg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 µg/ml compared to <2 µg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission.

Hepatitis C Screening Rate Among Underserved Adults With Serious Mental Illness Receiving Care in California Community Mental Health Centers.

Although HCV is more prevalent among people with severe mental illness (SMI; e.g., schizophrenia, bipolar disorder) than in the general population (17% vs 1%), no large previous studies have examined HCV screening in this population. In this cross-sectional study, we examined administrative data for 57 170 California Medicaid enrollees with SMI to identify prevalence and predictors of HCV screening from October 2010 through September 2011. Only 4.7% (2674 of 57 170) received HCV screening, with strongest predictors being nonpsychiatric health care utilization and comorbid substance abuse.

Association of the quality of interpersonal care during family planning counseling with contraceptive use.

BACKGROUND: Health communication and interpersonal skills are increasingly emphasized in the measurement of health care quality, yet there is limited research on the association of interpersonal care with health outcomes. As approximately 50% of pregnancies in the United States are unintended, whether interpersonal communication influences contraceptive use is of public health importance. OBJECTIVE: The aim of this study was to determine whether the quality of interpersonal care during contraceptive counseling is associated with contraceptive use over time. STUDY DESIGN: The Patient-Provider Communication about Contraception study is a prospective cohort study of 348 English-speaking women seen for contraceptive care, conducted between 2009 and 2012 in the San Francisco Bay Area. Quality of communication was assessed using a patient-reported interpersonal quality in family planning care measure based on the dimensions of patient-centered care. In addition, the clinical visit was audio recorded and its content coded according to the validated Four Habits Coding Scheme to assess interpersonal communication behaviors of clinicians. The outcome measures were 6-month continuation of the selected contraceptive method and use of a highly or moderately effective method at 6 months. Results were analyzed using mixed effect logistic regression models controlling for patient demographics, the clinic and the provider at which the visit occurred, and the method selected. RESULTS: Patient participants had a mean age of 26.8 years (SD 6.9 years); 46% were white, 26% Latina, and 28% black. Almost two-thirds of participants had an income of <200% of the Federal Poverty Level. Most of the women (73%) were making visits to a provider whom they had not seen before. Of the patient participants, 41% were still using their chosen contraceptive method at 6-month follow-up. Patients who reported high interpersonal quality of family planning care were more likely to maintain use of their chosen contraceptive method (adjusted odds ratio [aOR], 1.8; 95% CI, 1.1-3.0) and to be using a highly or moderately effective method at 6 months (aOR, 2.0; 95% CI, 1.2-3.5). In addition, 2 of the Four Habits were associated with contraceptive continuation; "invests in the beginning" (aOR, 2.3; 95% CI, 1.2-4.3) and "elicits the patient's perspective" (aOR, 1.8; 95% CI, 1.0-3.2). CONCLUSION: Our study provides evidence that the quality of interpersonal care, measured using both patient report and observation of provider behaviors, influences contraceptive use. These results provide support for ongoing attention to interpersonal communication as an important aspect of health care quality. The associations of establishing rapport and eliciting the patient perspective with contraceptive continuation are suggestive of areas of focus for provider communication skills training for contraceptive care.

Consumption of Caffeinated Products and Cardiac Ectopy.

BACKGROUND: Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental. METHODS AND RESULTS: We studied Cardiovascular Health Study participants with a baseline food frequency assessment, 24-hour ambulatory electrocardiography (Holter) monitoring, and without persistent atrial fibrillation. Frequencies of habitual coffee, tea, and chocolate consumption were assessed using a picture-sort food frequency survey. The main outcomes were PACs/h and PVCs/hour. Among 1388 participants (46% male, mean age 72 years), 840 (61%) consumed ≥1 caffeinated product per day. The median numbers of PACs and PVCs/h and interquartile ranges were 3 (1-12) and 1 (0-7), respectively. There were no differences in the number of PACs or PVCs/h across levels of coffee, tea, and chocolate consumption. After adjustment for potential confounders, more frequent consumption of these products was not associated with ectopy. In examining combined dietary intake of coffee, tea, and chocolate as a continuous measure, no relationships were observed after multivariable adjustment: 0.48% fewer PACs/h (95% CI -4.60 to 3.64) and 2.87% fewer PVCs/h (95% CI -8.18 to 2.43) per 1-serving/week increase in consumption. CONCLUSIONS: In the largest study to evaluate dietary patterns and quantify cardiac ectopy using 24-hour Holter monitoring, we found no relationship between chronic consumption of caffeinated products and ectopy.

Device-guided slow-paced respiration for menopausal hot flushes: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of device-guided slow-paced respiration for reducing the frequency and severity of menopausal hot flushes. METHODS: Perimenopausal or postmenopausal women reporting four or more hot flushes per day were recruited into a parallel-group, randomized trial of slow-paced respiration using a portable guided-breathing device. Women were randomly assigned to use a standard device to practice slowing their resting breathing rate to less than 10 breaths per minute for at least 15 minutes everyday or use an identical-appearing control device programmed to play relaxing nonrhythmic music while monitoring spontaneous breathing. The primary outcome, change in hot flush frequency over 12 weeks, was assessed using data from validated 7-day diaries abstracted by blinded analysts. RESULTS: Among the 123 participants, mean age was 53.4 (±3.4) years. Women reported an average of 8.5 (±3.5) hot flushes per day at baseline. After 12 weeks, women randomized to paced respiration (n=61) reported an average reduction of 1.8 (95% confidence interval [CI] 0.9-2.6) hot flushes per day (-21%) compared with 3.0 (95% CI 2.1-3.8) hot flushes per day (-35%) in the music-listening group (n=62) (P=.048). Paced respiration was associated with a 19% decrease in frequency of moderate-to-severe hot flushes compared with a 44% decrease with music listening (P=.02). CONCLUSION: In this randomized trial, women assigned to device-guided slow-paced respiration reported modest improvements in the frequency and severity of their hot flushes, but the paced respiration intervention was significantly less effective than a music-listening intervention in decreasing the frequency and severity of these symptoms. LEVEL OF EVIDENCE: I.

Restorative yoga and metabolic risk factors: the Practicing Restorative Yoga vs. Stretching for the Metabolic Syndrome (PRYSMS) randomized trial.

AIMS: Intensive lifestyle change prevents type 2 diabetes but is difficult to sustain. Preliminary evidence suggests that yoga may improve metabolic factors. We tested a restorative yoga intervention vs. active stretching for metabolic outcomes. METHODS: In 2009-2012, we conducted a 48-week randomized trial comparing restorative yoga vs. stretching among underactive adults with the metabolic syndrome at the Universities of California, San Francisco and San Diego. We provided lifestyle counseling and a tapering series of 90-min group classes in the 24-week intervention period and 24-week maintenance period. Fasting and 2-h glucose, HbA1c, triglycerides, HDL-cholesterol, insulin, systolic blood pressure, visceral fat, and quality of life were assessed at baseline, 6- and 12-months. RESULTS: 180 participants were randomized and 135 (75%) completed the trial. At 12 months, fasting glucose decreased more in the yoga group than in the stretching group (-0.35 mmol/L vs. -0.03 mmol/L; p=0.002); there were no other significant differences between groups. At 6 months favorable changes within the yoga group included reductions in fasting glucose, insulin, and HbA1c and an increase in HDL-cholesterol that were not sustained at 1 year except changes in fasting glucose. The stretching group had a significant reduction in triglycerides at 6 months which was not sustained at 1 year but had improved quality of life at both time-points. CONCLUSIONS: Restorative yoga was marginally better than stretching for improving fasting glucose but not other metabolic factors.

Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease.

OBJECTIVE: The n-3 polyunsaturated fatty acids are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked proinflammatory state. We hypothesized that the n-3 polyunsaturated fatty acids content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort. METHODS: This was a cross-sectional study of subjects who presented to an outpatient vascular surgery clinic for evaluation of PAD. We used linear regression to evaluate the independent association between the omega-3 index, inflammatory biomarkers (C-reactive protein [CRP], intercellular adhesion molecule-1, interleukin-6, and tumor-necrosis-factor-α) and endothelial function (brachial artery flow mediated dilation). RESULTS: 64 subjects (61 claudicants and three with critical limb ischemia) were recruited for the study. The mean CRP level was 5.0 ± 5.0 mg/L, and the mean omega-3 index was 5.0% ± 1.8%. In an unadjusted model, the omega-3 index was negatively associated with CRP (38% increase in CRP for one standard deviation decrease in the omega-3 index; P = .007), which remained significant after adjustment for age, body mass index, smoking, ankle-brachial index, and high-density lipoprotein (33%; P = .04). There was also evidence for independent associations between the omega-3 index and IL-6 (P = .001). There were no significant associations between the omega-3 index and vascular function tests. CONCLUSIONS: In a cohort of patients with PAD, the omega-3 index was inversely associated with biomarkers of inflammation even after adjustment for covariates including the ankle-brachial index. Because patients with PAD have a high inflammatory burden, further studies should be conducted to determine if manipulation of omega-3 index via dietary changes or fish oil supplementation could improve inflammation and symptoms in these patients.

Urine calcium excretion, cardiovascular events, and mortality in outpatients with stable coronary artery disease (from the Heart and Soul study).

We sought to evaluate the association of urine calcium excretion (UCaE), which reflects systemic calcium absorption, with cardiovascular (CV) events and mortality in outpatients with prevalent coronary heart disease (CHD). Calcium supplementation is associated with vascular calcification and adverse CV outcomes in patients with end-stage renal disease. Recent studies have raised concern that this phenomenon may also extend to the general population. However, previous studies have assessed oral calcium intake, which correlates poorly with systemic calcium absorption. We measured UCaE from 24-hour urine collections provided by 903 outpatients who were recruited from 2000 to 2002. We used Cox proportional hazard models to evaluate the association of baseline UCaE with a primary end point of any CV event (myocardial infarction [MI], heart failure, stroke, or CV mortality). During a mean follow-up of 6 ± 3 years, 287 subjects (32%) had a CV event. After multivariate adjustment for demographics, traditional CV risk factors, and kidney function, there was no association between UCaE and the primary end point of any CV event (per 10-mg/day greater UCaE, hazard ratio 1.00, 95% confidence interval 0.98 to 1.02). Evaluation of individual CV outcomes revealed a lower rate of MI with higher UCaE (hazard ratio 0.97, 95% confidence interval 0.94 to 1.00). In conclusion, greater UCaE is not associated with higher overall CV event rates or mortality in outpatients with stable CHD. On the contrary, greater UCaE is associated with a modestly lower rate of MI. These findings suggest that greater systemic calcium absorption does not confer CV harm in outpatients with prevalent CHD.

Efficacy of phototherapy for newborns with hyperbilirubinemia: a cautionary example of an instrumental variable analysis.

BACKGROUND: Use of instrumental variables is gaining popularity as a method of controlling for confounding by indication in observational studies of treatments. OBJECTIVES: To illustrate how unmeasured instrument-level treatment substitution can distort effect size estimates using as an example an instrumental variable analysis of phototherapy for neonatal jaundice. DESIGN: Retrospective cohort study. SETTING: Northern California Kaiser Permanente Hospitals. PATIENTS: The authors studied 20,731 newborns ≥ 2000 g and ≥ 35 weeks' gestation born 1995-2004 with a "qualifying" total serum bilirubin (TSB) level within 3 mg/dL of the 2004 American Academy of Pediatrics (AAP) phototherapy threshold who did not have a positive direct antiglobulin test. MEASUREMENTS: The intervention was inpatient phototherapy within 8 hours of the qualifying TSB. The outcome was a TSB level exceeding the AAP exchange transfusion threshold <48 hours from the qualifying TSB. The instrumental variable was a measure of the frequency of phototherapy use at the newborn's birth hospital. The unmeasured substituted treatment was supplementation with infant formula, assessed by chart review in a sample from the same cohort. RESULTS: In total, 128 infants (0.62%) exceeded the exchange transfusion threshold. Logistic and propensity analyses yielded crude odds ratios of ~0.5 for phototherapy efficacy, decreasing to ~0.2 with control for confounding by indication. Instrumental variable analyses suggested much greater phototherapy efficacy (e.g., odds ratios of 0.02-0.05). However, chart reviews revealed greater use of infant formula (which also lowers bilirubin levels) in hospitals that used more phototherapy (r = 0.56; P = 0.02), an association not present at the individual level (r = 0.13). CONCLUSIONS: Instrumental variable analyses may provide biased estimates of treatment efficacy if there are cointerventions or confounders associated with treatment at the level of the instrument, although even when these associations may not exist in individuals.

MF101, a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes: a phase II clinical trial.

OBJECTIVE: To determine the optimal dose, safety, and efficacy of an estrogen receptor beta selective Chinese herbal extract, menopausal formula 101 (MF101), for treating hot flushes. METHODS: A randomized, blinded trial in 217 postmenopausal women with hot flushes randomized to 5 or 10 g/day of MF101 or placebo for 12 weeks. RESULTS: The effects of 5 g/day of MF101 did not differ from those of placebo. After 12 weeks, the mean percent decrease in frequency of hot flushes in the 10 g/day group was 12.9% greater than that in the placebo group (P = 0.15), the median percent decrease was 11.7% greater than that in the placebo group (P = 0.05), and the proportion of women with at least a 50% reduction in hot flushes was 16.2% greater than that in the placebo group (P = 0.03). CONCLUSIONS: Treatment with 10 g/day of MF101 reduces the frequency of hot flushes. Trials with higher doses are planned.