Connecting Youth and Young Adults to Optimize Antiretroviral Therapy Adherence (YouTHrive): Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite intensive efforts to engage people living with HIV in the United States, less than half of the youth aged 13 to 24 years achieve viral suppression. There is a clear and continued need for innovative behavioral programs that support optimizing adherence among young persons with HIV. OBJECTIVE: There are 3 phases of this project. Phase 1 involves conducting focus groups to obtain feedback from youth about an existing technology-based antiretroviral therapy (ART) adherence intervention. Phase 2 will be used to conduct beta testing with youth to refine and finalize the YouTHrive (YT) intervention. Phase 3 is a randomized controlled trial (RCT) to test the efficacy of the YT intervention among youth living with HIV (YLWH). METHODS: In phase 1, we will conduct 6 focus groups with approximately 8 youths (aged 15-19 years) and young adults (aged 20-24 years), each in 3 US cities to obtain (1) feedback from YLWH about the look and feel and content of an existing adult-focused Web-based ART adherence intervention and (2) suggestions for adapting the intervention for YLWH similar to themselves. Phase 2 will involve updating the existing intervention to include features and functionality recommended by YLWH in phase 1; it will conclude with beta testing with 12 participants to gain feedback on the overall design and ensure proper functionality and ease of navigation. For phase 3, we will enroll 300 YLWH in 6 US cities (Atlanta, Chicago, Houston, New York City, Philadelphia, and Tampa) into a 2-arm prospective RCT. Participants will be randomized 1:1 to YT intervention or control group. The randomization sequence will be stratified by city and use random permuted blocks of sizes 2 and 4. Participants randomized to the control condition will view a weekly email newsletter on topics related to HIV, with the exception of ART adherence, for 5 months. Participants randomized to the YT intervention condition will be given access to the YT site for 5 months. Study assessments will occur at enrollment and 5, 8, and 11 months post enrollment. The primary outcome that will be assessed is sustained viral load (VL), defined as the proportion of participants in each study arm who have suppressed VL at both the 5- and 11-month assessment; the secondary outcome that will be assessed is suppressed VL at both the 5- and 11-month assessment between drug-using and nondrug-using participants assigned to the YT intervention arm. RESULTS: Participant recruitment began in May 2017 for phase 1 of the study. The data collection for aim 3 is anticipated to end in April 2020. CONCLUSIONS: The efficacy trial of the YT intervention will help to fill gaps in understanding the efficacy of mobile interventions to improve ART adherence among at-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03149757; https://clinicaltrials.gov/ct2/show/NCT03149757 (Archived by WebCite at http://www.webcitation.org/73pw57Cf1). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11502.

Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism.

Essentials Bleeding risk by anticoagulant choice for cancer-associated venous thrombosis (CA-VTE) is unknown. 26 894 people with CA-VTE were followed for bleeding in a claims database in the United States. Hospitalized bleeding risk was similar with direct acting oral anticoagulants vs. warfarin. Relative hospitalized bleeding risk varied by cancer type and anticoagulant choice. SUMMARY: Background Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE). Objective To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates. Patients/Methods We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty. Results Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69-1.11 and 0.98; 0.85-1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66-1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers. Conclusions In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.

Force of infection of Helicobacter pylori in Mexico: evidence from a national survey using a hierarchical Bayesian model.

Helicobacter pylori (H. pylori) is present in the stomach of half of the world's population. The force of infection describes the rate at which susceptibles acquire infection. In this article, we estimated the age-specific force of infection of H. pylori in Mexico. Data came from a national H. pylori seroepidemiology survey collected in Mexico in 1987-88. We modelled the number of individuals with H. pylori at a given age as a binomial random variable. We assumed that the cumulative risk of infection by a given age follows a modified exponential catalytic model, allowing some fraction of the population to remain uninfected. The cumulative risk of infection was modelled for each state in Mexico and were shrunk towards the overall national cumulative risk curve using Bayesian hierarchical models. The proportion of the population that can be infected (i.e. susceptible population) is 85.9% (95% credible interval (CR) 84.3%-87.5%). The constant rate of infection per year of age among the susceptible population is 0.092 (95% CR 0.084-0.100). The estimated force of infection was highest at birth 0.079 (95% CR 0.071-0.087) decreasing to zero as age increases. This Bayesian hierarchical model allows stable estimation of state-specific force of infection by pooling information between the states, resulting in more realistic estimates.

Taller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis.

Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30-40% for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. SUMMARY: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case-control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11-1.46), 1.34 (95% CI 1.04-1.73) and 1.45 (95% CI 1.04-2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.

Obesity and time to pregnancy.

BACKGROUND: Obesity may reduce fecundity. We examined the obesity-fecundity association in relation to menstrual cycle regularity, parity, smoking habits and age to gain insight into mechanisms and susceptible subgroups. METHODS: Data were provided by 7327 pregnant women enrolled in the Collaborative Perinatal Project at 12 study centres in the United States from 1959 to 1965. Prepregnancy body mass index (BMI) was analysed continuously and categorically [underweight (<18.5 kg/m2), optimal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obese (>or=30.0 kg/m2)]. Adjusted fecundability odds ratios (FORs) were estimated using Cox proportional hazards modelling for discrete time data. RESULTS: Fecundity was reduced for overweight [OR=0.92, 95% confidence interval (95% CI): 0.84, 1.01] and obese (OR=0.82, 95% CI: 0.72, 0.95) women compared with optimal weight women and was more evident for obese primiparous women (OR=0.66, 95% CI: 0.49, 0.89). Fecundity remained reduced for overweight and obese women with normal menstrual cycles. Neither smoking habits nor age modified the association. CONCLUSIONS: Obesity was associated with reduced fecundity for all subgroups of women and persisted for women with regular cycles. Our results suggest that weight loss could increase fecundity for overweight and obese women, regardless of menstrual cycle regularity, parity, smoking habits and age.

Discharge disposition from acute care after traumatic brain injury: the effect of insurance type.

OBJECTIVE: To determine if persons with traumatic brain injury (TBI) who are insured by Medicaid or health maintenance organizations (HMOs) are more likely to receive postacute care in skilled nursing facilities (SNFs) than in rehabilitation facilities, compared with persons insured by commercial fee-for-service (FFS) plans. DESIGN: Retrospective cohort study. SETTING: County hospital admitting 30% of all Washington State TBI patients. PATIENTS: Patients with moderate to severe TBI discharged to rehabilitation facilities or SNFs between 1992 and 1997 (n = 1271); 56.3% were insured by Medicaid, 26.1% by FFS plans, and 17.6% by HMOs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disposition on discharge from acute care (rehabilitation facilities vs SNF); adjusted relative risk (RR) and confidence interval (CI) for different insurance types. RESULTS: After accounting for confounding factors, Medicaid patients were 68% more likely (RR = 1.68, 95% CI = 1.34-2.11) and HMO patients were 23% more likely (RR = 1.23, 95% CI =.90-1.68) to go to a SNF than FFS patients. However, the latter difference was not statistically significant. CONCLUSIONS: An association exists between insurance type and postacute care site. Efforts should be made to determine the effect this relationship has on the cost and outcomes for TBI patients.

Using medicare databases for outcomes research in rehabilitation medicine.

With the advent of computerized billing for healthcare services, claims data have become useful in academic medicine. One of the largest suppliers of these types of data is Medicare, the US Government's healthcare insurance organization for the elderly and disabled. Because Medicare patients often require rehabilitation, this type of data can be useful in rehabilitation outcomes studies. Despite several significant limitations to Medicare billing data, Medicare claims data are powerful tools with which to analyze concepts in physical medicine and rehabilitation.

Empiric antibiotic therapy and mortality among medicare pneumonia inpatients in 10 western states : 1993, 1995, and 1997.

STUDY OBJECTIVES: To examine the association of empiric inpatient antibiotic treatment of community-acquired pneumonia (CAP) with mortality, and whether this association varies from year to year. DESIGN: Population-based, retrospective study adjusting for demographics, comorbidities, and clinical characteristics. SETTING: Acute-care hospitals in 10 western states. PATIENTS: A group of 10,069 Medicare beneficiaries aged > or = 65 years who were hospitalized with CAP during fiscal years 1993, 1995, and 1997. MEASUREMENTS AND RESULTS: We examined the risk for mortality during the 30 days after admission to the hospital. The impact of specific antibiotic regimens varied greatly from year to year. In 1993, therapy with a macrolide plus a beta-lactam was associated with significantly lower mortality than therapy with either a beta-lactam alone (adjusted odds ratio [AOR], 0.42; 95% confidence interval [CI], 0.25 to 0.69) or other regimens that did not include a macrolide, beta-lactam, or fluoroquinolone (AOR, 0.35; 95% CI, 0.20 to 0.62). Those associations were not observed in 1995 or 1997. Lower mortality was associated with fluoroquinolone monotherapy compared with beta-lactam monotherapy in 1997 (AOR, 0.27; 95% CI, 0.07 to 0.96) and with macrolide monotherapy compared with other regimens in 1995 (AOR, 0.24; 95% CI, 0.06 to 0.93), but the number of patients who received these regimens was small. CONCLUSIONS: The inclusion of a macrolide or a fluoroquinolone in initial empiric CAP treatment was associated with improved survival, but this association varied from year to year, perhaps as a result of a temporal variation in the incidence of atypical pathogen pneumonia. Improved testing and surveillance for atypical pathogen pneumonia are needed to guide empiric therapy.

Treatment of acute myocardial infarction and 30-day mortality among women and men.

BACKGROUND: Previous studies have suggested that women with acute myocardial infarction receive less aggressive therapy than men. We used data from the Cooperative Cardiovascular Project to determine whether women and men who were ideal candidates for therapy after acute myocardial infarction were treated differently. METHODS: Information was abstracted from the charts of 138,956 Medicare beneficiaries (49 percent of them women) who had an acute myocardial infarction in 1994 or 1995. Multivariate analysis was used to assess differences between women and men in the medications administered, the procedures used, the assignment of do-not-resuscitate status, and 30-day mortality. RESULTS: Among ideal candidates for therapy, women in all age groups were less likely to undergo diagnostic catheterization than men. The difference was especially pronounced among older women; for a woman 85 years of age or older, the adjusted relative risk was 0.75 (95 percent confidence interval, 0.68 to 0.83). Women were somewhat less likely than men to receive thrombolytic therapy within 60 minutes (adjusted relative risk, 0.93; 95 percent confidence interval, 0.90 to 0.96) or to receive aspirin within 24 hours after arrival at the hospital (adjusted relative risk, 0.96; 95 percent confidence interval, 0.95 to 0.97), but they were equally likely to receive beta-blockers (adjusted relative risk, 0.99; 95 percent confidence interval, 0.95 to 1.03) and somewhat more likely to receive angiotensin-converting-enzyme inhibitors (adjusted relative risk, 1.05; 95 percent confidence interval, 1.02 to 1.08). Women were more likely than men to have a do-not-resuscitate order in their records (adjusted relative risk, 1.26; 95 percent confidence interval, 1.22 to 1.29). After adjustment, women and men had similar 30-day mortality rates (hazard ratio, 1.02; 95 percent confidence interval, 0.99 to 1.04). CONCLUSIONS: As compared with men, women receive somewhat less aggressive treatment during the early management of acute myocardial infarction. However, many of these differences are small, and there is no apparent effect on early mortality.

Weighted health status in the Medicare population: development of the Weighted Health Index for the Medicare Current Beneficiary Survey (WHIMCBS).

We present an approach to constructing an aggregate index of health at the population level with data from Medicare beneficiaries using the 1991 (N = 12,667), 1995 (N = 15,590), and 1997 (N=17,058) Medicare Current Beneficiary Survey (MCBS). Similar to other work with survey data, we develop a weighted health status index from which one can calculate a point in time health status score for any beneficiary. Scores range from 1.0, representing "excellent health and no activity limitation", to 0.0, representing deceased. Sequences of numerically weighted health states experienced over time can be summed to calculate years of healthy life for beneficiaries. We test both the stability of the scoring system when developed on independent samples, as well as the sensitivity of years of healthy life calculations to changes in scoring assumptions. Findings suggest that, in addition to mortality, morbidity appears to play a significant role in the years of healthy life accrued by Medicare beneficiaries since entry into the Medicare program. Further, the index scoring system is highly stable when derived on independent samples. Finally, calculations of years of healthy life are robust to changes in scoring assumptions. The weighted health index for Medicare current beneficiaries (WHIMCBS) is a stable overall index of health and may be a useful ongoing indicator of health within the Medicare population.

Do Medicare patients with disabilities receive preventive services? A population-based study.

OBJECTIVE: To compare health maintenance procedure rates of Medicare patients with different levels of disability. STUDY DESIGN: Observational study analyzing data from the 1995 Medicare Current Beneficiary Survey (MCBS, n = 15,590). Self-reported Pap smears, mammograms, and influenza and pneumococcal vaccinations were compared between groups with different levels of health-related difficulties in six activities of daily living (ADL). RESULTS: Compared to those without disabilities, the most severely disabled women (limitations in 5 or 6 ADL) reported fewer Pap smears (age < or =70, 23% vs 41%, p < .001) and mammograms (age > or = 50, 13% vs 44%, p < .001). In a controlled analysis, individuals with this high level of disability were 57% (95% confidence interval [CI], 33% to 72%) and 56% (95% CI, 43% to 76%) less likely to report receiving Pap smears and mammograms, respectively, compared with able-bodied women, regardless of their age, whether they were in an HMO, or whether they lived in a long-term care facility. Functional limitations were not a deterrent to receiving vaccinations. In general, patients in HMOs reported more procedures than those in fee-for-service, while those in long-term care facilities reported fewer procedures than those living in the community. CONCLUSIONS: Disability among Medicare patients is a significant, independent risk factor for not receiving mammograms and Pap smears. Efforts should be made to identify the most severely disabled because they are at particular risk.

Risk factors for cervical intraepithelial neoplasm in Alaska Native women: a pilot study.

Although rates for invasive cervical cancer have declined over the past twenty years among Alaska Native women, they continue to show high rates of pre-invasive cervical lesions (cervical intraepithelial neoplasia, or CIN). We investigated risk factors for CIN II/III among Alaska Native women in a pilot case-control study. Cases (n = 26) included women with biopsy-proven CIN II/III, while controls (n = 52) had normal cervical epithelium. The strongest risks associated with CIN II/III were HPV infection of any type (Crude Odds Ratio [OR] 8.4, 95% Confidence Interval [CI]: 2.9-29.4), HPV 16 infection (OR 40.8, 95% CI: 9.4-176.4), and a family history of cervical dysplasia (OR 3.9, 95% CI: 1.3-11.3). We also found that use of depot-medroxy progesterone acetate was associated with CIN (OR 3.0, 95% CI: 1.1-8.5). A larger investigation would be necessary to allow adequate evaluation of these, and other, risk factors for CIN among Alaska Native women.