The Cost-Effectiveness of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in the COMPASS Trial: A US Perspective.

BACKGROUND: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. METHODS: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. RESULTS: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. CONCLUSION: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424.

The impact of statistical properties of incremental monetary net benefit and incremental cost-effectiveness ratio on health economic modeling choices.

INTRODUCTION: There is controversy on whether to use incremental monetary net benefit (INMB) or incremental cost-effectiveness ratio (ICER) in health economic evaluations alongside randomized controlled trials. We studied the impact of restricted mean survival time (RMST) on the long-term projection of INMB and ICER. METHODS: We analyzed the unbiasedness and efficiency of ICER and INMB by (1) deriving the metrics' expected values and variances based on theoretical probability distributions, (2) simulating their 15-year post-trial projections based on between-arm-RMST-gained through a 2 × 4 × 2 factorial experiment of Markov 2-state microsimulations. Simulations and comparison were run on the data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). RESULTS: Our simulation findings using RMST showed that ICER was more efficient than INMB, regardless of disease populations, time horizon, modeling choices, and underlying probability distributions of incremental mean cost and effect. ICER had a small variance and thus showed its robustness to the choices of models. CONCLUSION: INMB's variance varies with a willingness-to-pay (WTP) threshold quadratically while ICER's variance with a WTP threshold value quadratically while ICER's variance with incremental-mean-cost quadratically. A simple and naïve model can sufficiently estimate ICER. Future metrics are expected to be health-economic-meaningful, unambiguous, unbiased, efficient, and statistical-inference-friendly.

The cost-effectiveness of rivaroxaban with or without aspirin in the COMPASS trial.

AIMS: The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial demonstrated that rivaroxaban 2.5 mg BID with aspirin 100 mg was more effective than aspirin 100 mg daily alone for the prevention of cardiovascular (CV) death, stroke, or myocardial infarction in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We aimed to examine the cost-effectiveness of rivaroxaban using patient-level data from the COMPASS trial. METHODS AND RESULTS: We performed an in-trial analysis and extrapolated our results for 33 years using a two-state Markov model with a 1-year cycle length. Hospitalization events, procedures, and study drugs were documented for patients. We applied country-specific (Canada, France, and Germany) direct healthcare system costs (in USD) to healthcare resources consumed by patients. Average cost per patient during the trial (mean follow-up of 23 months), quality-adjusted life years (QALYs), and lifetime cost-effectiveness were calculated. Costs of events and procedures were reduced with rivaroxaban 2.5 mg BID with aspirin. The addition of rivaroxaban 2.5 mg BID increased total costs for the combination group. Over a lifetime horizon (in trial +33 years), rivaroxaban plus aspirin was associated with 1.17 QALYs gained, yielding an incremental cost-effectiveness ratio (ICER) of $3946/QALY, $9962/QALY, and $10 264/QALY in Canada, France, and Germany, respectively. PAD and polyvascular disease subgroups had lower ICERs. CONCLUSION: Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduces direct healthcare costs. After acquisition costs of rivaroxaban, the lifetime cost-effectiveness of 2.5 mg twice daily plus aspirin is highly cost-effective in Canada, France, and Germany.(COMPASS ClinicalTrials.gov identifier: NCT01776424).

Projecting effectiveness after ending a randomized controlled trial: a two-state Markov microsimulation model.

OBJECTIVE: To investigate the behavior of restricted mean survival time (RMST) and designs of a two-state Markov microsimulation model through a 2 × 4 × 2 full factorial experiment. METHOD: By projecting patient-wise 15-year-post-trial survival, we estimated life-year-gained between an intervention and a control group using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Projections considered either in-trial events or post-trial medications. They were compared based on three factors: (i) choice of probability of death, (ii) lengths of cycle, and (iii) usage of half-a-cycle age correction. Three-way analysis of variance and post-hoc Tukey's Honest Significant Difference test compared means among factors. RESULTS: When both in-trial events and post-trial study medications were considered, monthly, quarterly, or semiannually were not different from one other in projected life-year-gained. However, the annual one was different from the others: mean and 95 percent confidence interval 252.2 (190.5-313.9) days monthly, 251.8 (192.0-311.6) quarterly, 249.1 (189.7-308.5) semiannually, and 240.8 (178.5-303.1) annually. The other two factors also impacted life-year-gained: background probability (269.1 [260.3-277.9] days projected with REACH-based-probabilities, 227.7 [212.6-242.8] with a USA life table); half-a-cycle age correction (245.5 [199.0-292] with correction and 251.4 [209.1-293.7] without correction). When not considering post-trial medications, only the choice of probability of death appeared to impact life-year-gained. CONCLUSION: For a large trial or cohort, to optimally project life-year-gained, one should consider using (i) annual projections, (ii) life table probabilities, (iii) in-trial events, and (iv) post-trial medication use.

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study.

BACKGROUND: Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. METHODS: In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. FINDINGS: Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96-1·58) for high-income countries, 1·59 (1·42-1·78) in middle-income countries, and 2·23 (1·79-2·77) in low-income countries (pinteraction<0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14-1·98) for high-income countries, 1·80 (1·58-2·06) in middle-income countries, and 2·76 (2·29-3·31) in low-income countries (pinteraction<0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (pinteraction<0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries. INTERPRETATION: Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Decoding and modelling of time series count data using Poisson hidden Markov model and Markov ordinal logistic regression models.

Hidden Markov models are stochastic models in which the observations are assumed to follow a mixture distribution, but the parameters of the components are governed by a Markov chain which is unobservable. The issues related to the estimation of Poisson-hidden Markov models in which the observations are coming from mixture of Poisson distributions and the parameters of the component Poisson distributions are governed by an m-state Markov chain with an unknown transition probability matrix are explained here. These methods were applied to the data on Vibrio cholerae counts reported every month for 11-year span at Christian Medical College, Vellore, India. Using Viterbi algorithm, the best estimate of the state sequence was obtained and hence the transition probability matrix. The mean passage time between the states were estimated. The 95% confidence interval for the mean passage time was estimated via Monte Carlo simulation. The three hidden states of the estimated Markov chain are labelled as 'Low', 'Moderate' and 'High' with the mean counts of 1.4, 6.6 and 20.2 and the estimated average duration of stay of 3, 3 and 4 months, respectively. Environmental risk factors were studied using Markov ordinal logistic regression analysis. No significant association was found between disease severity levels and climate components.

Feasibility of Assessing Falls Risk and Promoting Falls Prevention in Beauty Salons.

Falls are a major public health risk and a leading cause of emergency room visits for people of all ages. Finding ways to increase access to information and evidence-based falls prevention strategies is critically important across the lifespan. We tested the feasibility of conducting a falls risk assessment and awareness program among customers who attend beauty salons. We enrolled 78 customers from 2 beauty salons who completed a written questionnaire as well as several biometric and functional balance tests designed to assess falls risk. On average, enrolled participants were 56 years of age (range: 19-90), female (n = 70, 91%), and Black (n = 47, 62%). Eleven percent of enrolled customers were classified as at high risk of falls because they had reported two or more falls in the last 6 months. We found that younger age, higher education, employment, moderate physical activity, and decreased frequency of salon visits were associated with fewer falls. Results demonstrated initial interest in, and the feasibility of recruiting and enrolling customers into a beauty salon-based falls risk assessment and awareness program. Beauty salons, which are in all communities, represent an innovative setting for reaching people of all ages with life-saving falls prevention information and services.

Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering. FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality. INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings. FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

DOWRY DEMAND AND HARASSMENT: PREVALENCE AND RISK FACTORS IN INDIA.

The practice of dowry is widespread in India and refers to the payment of cash/gifts by the bride's family to the bridegroom's family before marriage. Though prohibited by law, dowry is widely practised, and often contributes to severe injuries and even death of young brides. This study examined the prevalence and risk factors for dowry demand and dowry harassment and its psychosocial correlates across different social strata in India, and also by husband and mother-in-law characteristics. In a cross-sectional survey of 9938 women in rural, urban and urban non-slum sites across India conducted in 1998-99, dowry demand was found to be significantly higher (p<0.001) in the urban non-slum and rural areas (26% and 23% respectively) than in urban slum areas (18%). Overall, 17% of groom's families were not satisfied with the dowry, this being higher in rural areas (21%) than in urban slum and non-slum areas (about 14% in both). The overall prevalence of dowry harassment among this group of women was 13.3%. Mothers-in-law who had themselves experienced dowry demand were 14 (95% CI 5.0-40.4) and 5 (95% CI 1.3-18.9) times more likely to demand and harass daughters-in-law over dowry, respectively. Another significant risk factor for dowry-related harassment was mother-in law's status in the family. Interventions related to modifiable risk factors, such as increased social support at the community level, should help reduce dowry harassment.

The keys to healthy family child care homes intervention: study design and rationale.

BACKGROUND: Obesity is a major public health problem for which early preventive interventions are needed. Large numbers of young children are enrolled in some form of child care program, making these facilities influential environments in children's development. Family child care homes (FCCH) are a specific type of child care in which children are cared for within the provider's own residence. FCCHs serve approximately 1.5 million children in the U.S.; however, research to date has overlooked FCCH providers and their potential to positively influence children's health-related behaviors. METHODS: Keys to Healthy Family Child Care Homes (Keys) is a cluster-randomized controlled trial testing the efficacy of an intervention designed to help providers become healthy role models, provide quality food- and physical activity-supportive FCCH environments, and implement effective business practices. The intervention is delivered through workshops, home visits, tailored coaching calls, and educational toolkits. Primary outcomes are child physical activity measured via accelerometry data and dietary intake data collected using direct observation at the FCCH. Secondary outcomes include child body mass index, provider weight-related behaviors, and observed obesogenic environmental characteristics. CONCLUSION: Keys is an innovative approach to promoting healthy eating and physical activity in young children. The intervention operates in a novel setting, targets children during a key developmental period, and addresses both provider and child behaviors to synergistically promote health.

A comparison of live counseling with a web-based lifestyle and medication intervention to reduce coronary heart disease risk: a randomized clinical trial.

IMPORTANCE: Most primary care clinicians lack the skills and resources to offer effective lifestyle and medication (L&M) counseling to reduce coronary heart disease (CHD) risk. Thus, effective and feasible CHD prevention programs are needed for typical practice settings. OBJECTIVE: To assess the effectiveness, acceptability, and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats. DESIGN, SETTING, AND PARTICIPANTS: A comparative effectiveness trial in 5 diverse family medicine practices in North Carolina. Participants were established patients, aged 35 to 79 years, with no known cardiovascular disease, and at moderate to high risk for CHD (10-year Framingham Risk Score [FRS], ≥10%). INTERVENTIONS: Participants were randomized to counselor-delivered or web-based format, each including 4 intensive and 3 maintenance sessions. After randomization, both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies. Participants chose the risk-reducing strategies they wished to follow. MAIN OUTCOMES AND MEASURES: The primary outcome was within-group change in FRS at 4-month follow-up. Other measures included standardized assessments of blood pressure, blood lipid levels, lifestyle behaviors, and medication adherence. Acceptability and cost-effectiveness were also assessed. Outcomes were assessed at 4 and 12 months. RESULTS: Of 2274 screened patients, 385 were randomized (192 counselor; 193 web): mean age, 62 years; 24% African American; and mean FRS, 16.9%. Follow-up at 4 and 12 months included 91% and 87% of the randomized participants, respectively. There was a sustained reduction in FRS at both 4 months (primary outcome) and 12 months for both counselor-based (-2.3% [95% CI, -3.0% to -1.6%] and -1.9% [95% CI, -2.8% to -1.1%], respectively) and web-based groups (-1.5% [95% CI, -2.2% to -0.9%] and -1.7% [95% CI, -2.6% to -0.8%] respectively). At 4 months, the adjusted difference in FRS between groups was -1.0% (95% CI, -1.8% to -0.1%) (P = .03), and at 12 months, it was -0.6% (95% CI, -1.7% to 0.5%) (P = .30). The 12-month costs from the payer perspective were $207 and $110 per person for the counselor- and web-based interventions, respectively. CONCLUSIONS AND RELEVANCE: Both intervention formats reduced CHD risk through 12-month follow-up. The web format was less expensive. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01245686.

Smoking among U.S. Hispanic/Latino adults: the Hispanic community health study/study of Latinos.

BACKGROUND: Prior national surveys capture smoking behaviors of the aggregated U.S. Hispanic/Latino population, possibly obscuring subgroup variation. PURPOSE: To describe cigarette use among Hispanic/Latino adults across subgroups of age, gender, national background, SES, birthplace, and degree of acculturation to the dominant U.S. culture. METHODS: A cross-sectional survey of 16,322 participants in the Hispanic Community Health Study/Study of Latinos aged 18-74 years, recruited in Bronx NY, Chicago IL, Miami FL, and San Diego CA, was conducted during 2008-2011. RESULTS: Prevalence of current smoking was highest among Puerto Ricans (men, 35.0%; women, 32.6%) and Cubans (men, 31.3%; women, 21.9%), with particularly high smoking intensity noted among Cubans as measured by pack-years and cigarettes/day. Dominicans had the lowest smoking prevalence (men, 11.0%; women, 11.7%). Individuals of other national backgrounds had a smoking prevalence that was intermediate between these groups, and typically higher among men than women. Non-daily smoking was common, particularly although not exclusively among young men of Mexican background. Persons of low SES were more likely to smoke, less likely to have quit smoking, and less frequently used over-the-counter quit aids compared to those with higher income and education levels. Smoking was more common among individuals who were born in the U.S. and had a higher level of acculturation to the dominant U.S. culture, particularly among women. CONCLUSIONS: Smoking behaviors vary widely across Hispanic/Latino groups in the U.S., with a high prevalence of smoking among population subgroups with specific, readily identifiable characteristics.

Designing and implementing a comparative effectiveness study of two strategies for delivering high quality CHD prevention: methods and participant characteristics for the Heart to Health study.

BACKGROUND: Although lifestyle and medications are effective for coronary heart disease (CHD) risk reduction, few studies have examined the comparative effectiveness of various strategies for delivering high quality CHD risk reduction. In this paper, we report on the design and baseline characteristics of participants for just such a trial. METHODS: We conducted a randomized trial of the same lifestyle and medication intervention delivered in two alternate formats: counselor-delivered or web-based. The trial was conducted at 5 diverse practices in a family medicine research network and included men and women age 35-79 who were at high risk of CHD events based on 10-year predicted Framingham risk of ≥10% or a known history of cardiovascular disease. After individual-level randomization, participants in both arms received a decision aid plus four intensive intervention visits and 3 maintenance visits over 12 months. The primary outcome was change in 10-year predicted CHD risk among patients without prior cardiovascular disease. Secondary outcomes, measured among all participants, included changes in CHD risk factors, cost-effectiveness, and acceptability at 4 and 12-month follow-up. RESULTS: We randomized 489 eligible patients: 389 without and 100 with a known history of cardiovascular disease. Mean age was 62.3. 75% were white, 25% African-American. 45% had a college education. 88% had health insurance. Mean 10-year predicted CHD risk was 16.9%. CONCLUSION: We have successfully recruited a diverse sample of practices and patients that will provide a rich sample in which to test the comparative effectiveness of two strategies to implement high quality CHD prevention.

Partner burden in irritable bowel syndrome.

BACKGROUND & AIMS: Studies have described the burden experienced by caregivers and next of kin to patients with diseases such as cancer. However, the burden of functional gastrointestinal disorders on partners of patients has not been determined. We aimed to quantify the degree of burden to partners of patients with irritable bowel syndrome (IBS), to describe the factors that affect the burden perceived, and to identify the areas of relationship that are affected. METHODS: We surveyed 152 patients diagnosed with IBS at a tertiary gastrointestinal clinic, on the basis of Rome III criteria, and their partners. Their partners completed questionnaires including the Zarit Burden Interview (ZBI), Relationship Satisfaction Scale, and questions on sexual relationships. Patients with IBS were rated for disease severity by using the Functional Bowel Disease Severity Index. We compared findings with those from 39 partners of healthy individuals (controls). RESULTS: There were no significant demographic differences between the partners of patients with IBS and controls; demographics had no effect on burden. Burden was significantly higher among partners of IBS patients (mean ZBI score, 22.1) than controls (mean ZBI score, 11.5) (P = .0002). The degree of burden was directly related to IBS severity (P < .0001). There were inverse relationships between partners' rating of burden (ZBI) and relationship quality (R = -0.60; P < .001) and sexual satisfaction (R = -0.56; P < .0001). There was no difference in the Relationship Satisfaction Scale scores (4.25 vs 4.19; P = .78) or sexual relationship (6.47 vs 6.21; P = .64) between partners of IBS patients and controls, respectively. CONCLUSIONS: Partners of patients with IBS have a significant burden (on the basis of ZBI score), compared with partners of healthy individuals. Perceived burden increases with IBS severity and poorer sexual and relationship satisfaction.

Workdays lost due to occupational injuries among young workers in Brazil.

BACKGROUND: The severity of non-fatal work-related injuries has seldom been examined among young workers. We estimated the extent and distribution of workdays lost due to non-fatal work injuries using compensation data. METHODS: Data are from the Brazilian Institute of Social Insurance, for 2006. The study population is comprised of all insured workers of age 16-24. Descriptive statistics reflect workdays lost due to health-related disability, according to sex, age group, wage, and trade. RESULTS: Out of 4.8 million insured workers ages 16-24 years, we estimated 1,282,940 workdays lost. We observed a larger number of median workdays lost among males age 20-24 in retail and service trades (83 days) and among 16-19-year-old females in the agriculture/fish/forestry/cattle (142 days). CONCLUSIONS: Young workers experience a heavy burden of work-related injuries. Disability workdays may compromise school attendance and performance. Other potential impacts affect productivity and social insurance costs.

Characterization of episodes of irritable bowel syndrome using ecological momentary assessment.

OBJECTIVES: Patients with irritable bowel syndrome (IBS) report that symptoms occur as episodes. The nature and frequency of episodes have not been well studied. METHODS: Using modified ecological momentary assessment (EMA), we examined clinical factors attributed to IBS symptom episodes and compared them with nonsymptom episode periods in patients with IBS-D (N=21), IBS-C (N=18), or IBS-M (N=19), and healthy controls (N=19). Symptoms were rated over 14 days on a visual ordinal scale (VOS: 0-10) randomly in morning, midday, and evening, and at wake up, bedtime, prebowel movement, and postbowel movement. Scores were evaluated for total group and across subgroups and between EMA and daily diary cards on the same day. RESULTS: Subjects (n=57/59) reported symptom episodes 34% of the time. Episodes showed significantly higher pain levels (3.6 vs. 1.64, P<0.0001), bloating (4.57 vs. 3.02, P<0.0001), stress (3.54 vs. 2.59, P<0.0001), and decreased well-being (5.29 vs. 6.16, P<0.0001). Episode frequency/2 weeks was greatest for IBS-D (10.7±7.05) than IBS-C (8.4±5.76) and IBS-M (7.1±4.45) (P=nonsignificant). IBS-D also had shorter episodes (9 h 23 min) compared with IBS-M (15 h 01 min) and IBS-C (15 h 25 min) (P<0.04). Stool frequency and looser consistency were greater with IBS-D and similar between IBS-C and IBS-M. Abdominal pain was the greatest predictor of episode status. Diary card ratings of pain and stool frequency overestimate levels reported by EMA. CONCLUSIONS: Episodes of IBS are associated with greater pain (strongest relationship), bloating, and stress scores, and poorer global well-being. Compared with IBS-D, IBS-C and IBS-M are similar in clinical features. Patients overreport pain and stool frequency by diary compared with EMA.

NIH consensus development conference draft statement on vaginal birth after cesarean: new insights.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on vaginal birth after cesarean (VBAC). PARTICIPANTS: A non-DHHS, nonadvocate 15-member panel representing the fields of obstetrics and gynecology, urogynecology, maternal and fetal medicine, pediatrics, midwifery, clinical pharmacology, medical ethics, internal medicine, family medicine, perinatal and reproductive psychiatry, anesthesiology, nursing, biostatistics, epidemiology, health care regulation, risk management, and a public representative, and a public representative. In addition, 21 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Oregon Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: Given the available evidence, trial of labor is a reasonable option for many pregnant women with one prior low transverse uterine incision. The data reviewed in this report show that both trial of labor and elective repeat cesarean delivery for a pregnant woman with one prior transverse uterine incision have important risks and benefits and that these risks and benefits differ for the woman and her fetus. This poses a profound ethical dilemma for the woman, as well as her caregivers, because benefit for the woman may come at the price of increased risk for the fetus and vice versa. This conundrum is worsened by the general paucity of high-level evidence about both medical and nonmedical factors, which prevents the precise quantification of risks and benefits that might help to make an informed decision about trial of labor compared with elective repeat cesarean delivery. The panel was mindful of these clinical and ethical uncertainties in making the following conclusions and recommendations. One of the panel's major goals is to support pregnant women with one prior transverse uterine incision to make informed decisions about trial of labor compared with elective repeat cesarean delivery. The panel recommends that clinicians and other maternity care providers use the responses to the six questions, especially questions 3 and 4, to incorporate an evidence-based approach into the decisionmaking process. Information, including risk assessment, should be shared with the woman at a level and pace that she can understand. When trial of labor and elective repeat cesarean delivery are medically equivalent options, a shared decisionmaking process should be adopted and, whenever possible, the woman's preference should be honored. The panel is concerned about the barriers that women face in gaining access to clinicians and facilities that are able and willing to offer trial of labor. Given the low level of evidence for the requirement for "immediately available" surgical and anesthesia personnel in current guidelines, the panel recommends that the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists reassess this requirement with specific reference to other obstetric complications of comparable risk, risk stratification, and in light of limited physician and nursing resources. Healthcare organizations, physicians, and other clinicians should consider making public their trial of labor policies and VBAC rates, as well as their plans for responding to obstetric emergencies. The panel recommends that hospitals, maternity care providers, healthcare and professional liability insurers, consumers, and policymakers collaborate on the development of integrated services that could mitigate or even eliminate current barriers to trial of labor. The panel is concerned that medical-legal considerations add to, and in many instances exacerbate, these barriers to trial of labor. Policymakers, providers, and other stakeholders must collaborate in developing and implementing appropriate strategies to mitigate the chilling effect the medical-legal environment has on access to care. High-quality research is needed in many areas. The panel has identified areas that need attention in response to question 6. Research in these areas should be given appropriate priority and should be adequately funded--especially studies that would help to characterize more precisely the short-term and long-term maternal, fetal, and neonatal outcomes of trial of labor and elective repeat cesarean delivery.

Optimized probability sampling of study sites to improve generalizability in a multisite intervention trial.

INTRODUCTION: Studies of type 2 translation, the adaption of evidence-based interventions to real-world settings, should include representative study sites and staff to improve external validity. Sites for such studies are, however, often selected by convenience sampling, which limits generalizability. We used an optimized probability sampling protocol to select an unbiased, representative sample of study sites to prepare for a randomized trial of a weight loss intervention. METHODS: We invited North Carolina health departments within 200 miles of the research center to participate (N = 81). Of the 43 health departments that were eligible, 30 were interested in participating. To select a representative and feasible sample of 6 health departments that met inclusion criteria, we generated all combinations of 6 from the 30 health departments that were eligible and interested. From the subset of combinations that met inclusion criteria, we selected 1 at random. RESULTS: Of 593,775 possible combinations of 6 counties, 15,177 (3%) met inclusion criteria. Sites in the selected subset were similar to all eligible sites in terms of health department characteristics and county demographics. CONCLUSION: Optimized probability sampling improved generalizability by ensuring an unbiased and representative sample of study sites.

International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit.

BACKGROUND: Although clinicians generally make treatment decisions in irritable bowel syndrome (IBS) related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are not fully understood. OBJECTIVE: To describe among patients with IBS their symptoms and severity, quality of life and health status, medications taken, and the risk that they would take to continue medications for optimal relief. METHODS: Adult patients diagnosed with IBS who accessed the websites of the International Foundation for Functional GI Disorders or the University of North Carolina Center for Functional GI Disorders filled out questionnaires to address the study aims. RESULTS: The 1966 respondents (83% female, 91% white, 78% US/Canada) reported impaired health status: restricting on average 73 days of activity in a year, having poor health-related quality of life particularly with dietary restrictions, mood disturbance, and interference with daily activity, and 35% reported their symptoms as severe defined primarily as pain, bowel difficulties, bloating, and eating/dietary restrictions). These symptoms were reported in some combination by over 90%, and 35.1% endorsed all 4 items. To receive a treatment that would make them symptom free, patients would give up 25% of their remaining life (average 15 y) and 14% would risk a 1/1000 chance of death. Most of the medications being taken were for pain relief and 18% were taking narcotics. Complementary and alternative treatments were used by 37%. CONCLUSIONS: Patients accessing IBS informational websites report moderate-to-severe impairments in health status, and would take considerable risk to obtain symptom benefit. There is an unmet need to find effective treatments for patients with IBS and regulatory agencies might consider raising risk-benefit ratios when approving new medications for IBS.