Prescription and Dispensation of QT-Prolonging Medications in Individuals Receiving Hemodialysis.

Importance: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population. Objective: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis. Design, Setting, and Participants: This cross-sectional study included patients 60 years or older who were enrolled in Medicare Parts A, B, and D receiving in-center hemodialysis from January 1 to December 31, 2019. Analyses were conducted from October 20, 2022, to June 16, 2023. Exposures: New-user prescriptions for the 7 most frequently filled QT-prolonging medications characterized by the timing of the new prescription relative to acute care encounters, the type of prescribing clinician and pharmacy that dispensed the medication, and concomitant use of selected medications known to interact with the 7 most frequently filled QT-prolonging medications with known TdP risk. Main Outcomes and Measures: The main outcomes were the frequencies of the most commonly filled and new-use episodes of QT-prolonging medications; the timing of medication fills relative to acute care events; prescribers and dispensing pharmacy characteristics for new use of medications; and the frequency and types of new-use episodes with concurrent use of potentially interacting medications. Results: Of 20 761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10 992 (52.9%) filled a study drug prescription. Approximately 80% (from 78.6% for odansetron to 93.9% for escitalopram) of study drug new-use prescriptions occurred outside of an acute care event. Between 36.8% and 61.0% of individual prescriptions originated from general medicine clinicians. Between 16.4% and 26.2% of these prescriptions occurred with the use of another QT-prolonging medication. Most potentially interacting drugs were prescribed by different clinicians (46.3%-65.5%). Conclusions and Relevance: In this cross-sectional study, QT-prolonging medications for individuals with dialysis-dependent kidney failure were commonly prescribed by nonnephrology clinicians and from nonacute settings. Prescriptions for potentially interacting medications often originated from different prescribers. Strategies aimed at minimizing high-risk medication-prescribing practices in the population undergoing dialysis are needed.

Double-sided asymmetric metasurfaces achieving sub-microscale focusing from a GaN green laser diode.

We proposed and demonstrated a highly efficient sub-microscale focusing from a GaN green laser diode (LD) integrated with double-sided asymmetric metasurfaces. The metasurfaces consist of two nanostructures in a GaN substrate: nanogratings on one side and a geometric phase based metalens on the other side. When it was integrated on the edge emission facet of a GaN green LD, linearly polarized emission was firstly converted to the circularly polarized state by the nanogratings functioning as a quarter-wave plate, the phase gradient was then controlled by the metalens on the exit side. In the end, the double-sided asymmetric metasurfaces achieve a sub micro-focusing from linearly polarized states. Experimental results show the full width at half maximum of the focused spot size is about 738 nm at the wavelength 520 nm and the focusing efficiency is about 72.8%. Our results lay a foundation for the multi-functional applications in optical tweezers, laser direct writing, visible light communication, and biological chip.

Musculoskeletal diagnoses, comorbidities, and physical and occupational therapy use among older adults with and without cerebral palsy.

BACKGROUND: Musculoskeletal (MSK) disorder in adults with cerebral palsy (CP) is higher than in the general population. Evidence lacks about physical therapy (PT) and occupational therapy (OT) service utilization among older adults (65> years) living with CP. OBJECTIVE: We compared the presence of comorbidities and patterns of PT and OT use among older adults with and without CP seeking care for MSK disorders. METHODS: A 20% national sample of Medicare claims data (2011-2014) identified community-living older adults with (n = 8796) and without CP (n = 5,613,384) with one or more ambulatory claims for MSK diagnoses. The sample matched one CP case to two non-CP cases per year on MSK diagnoses, age, sex, race, dual eligibility, and census region. Exposure variable was the presence/absence of a CP diagnosis. Outcomes were use of PT and OT services identified via CPT and revenue center codes, and the presence/absence of Elixhauser comorbidities. RESULTS: In older adults with MSK diagnoses, less than a third regularly utilized PT and/or OT services, and adults with CP utilized significantly less PT than adults without CP, and for some MSK diagnoses had fewer visits than their matched peers. Older adults with CP were at greater risk for secondary conditions that influence morbidity, mortality, and quality of life compared to their age-matched peers without CP. CONCLUSIONS: Older adults with CP and MSK diagnoses had a greater prevalence of numerous comorbidities and lower use of PT services relative to their non-CP peers.

Long- and short-term weight change and incident coronary heart disease and ischemic stroke: the Atherosclerosis Risk in Communities Study.

Weight gain increases the prevalence of obesity, a risk factor for cardiovascular disease. Nevertheless, unintentional weight loss can be a harbinger of health problems. The Atherosclerosis Risk in Communities Study (1987-2009) included 15,792 US adults aged 45-64 years at baseline and was used to compare associations of long-term (30 years) and short-term (3 years) weight change with the risks of coronary heart disease (CHD) and ischemic stroke. Age-, gender-, and race-standardized incidence rates were 4.9 (95% confidence interval (CI): 4.6, 5.2) per 1,000 person-years for CHD and 2.5 (95% CI: 2.3, 2.8) per 1,000 person-years for stroke. After controlling for baseline body mass index and other covariates, long-term weight gain (since age 25 years) of more than 2.7% was associated with elevated CHD risk, and any long-term weight gain was associated with increased stroke risk. Among middle-aged adults, short-term (3-year) weight loss of more than 3% was associated with elevated immediate CHD risk (hazard ratio = 1.46, 95% CI: 1.18, 1.81) and stroke risk (hazard ratio = 1.45, 95% CI: 1.10, 1.92). Risk tended to be larger in adults whose weight loss did not occur through dieting. Avoidance of weight gain between early and middle adulthood can reduce risks of CHD and stroke, but short-term, unintentional weight loss in middle adulthood may be an indicator of immediate elevated risk that has not previously been well recognized.

Sample size and repeated measures required in studies of foods in the homes of African-American families.

Measurement of the home food environment is of interest to researchers because it affects food intake and is a feasible target for nutrition interventions. The objective of this study was to provide estimates to aid the calculation of sample size and number of repeated measures needed in studies of nutrients and foods in the home. We inventoried all foods in the homes of 80 African-American first-time mothers and determined 6 nutrient-related attributes. Sixty-three households were measured 3 times, 11 were measured twice, and 6 were measured once, producing 217 inventories collected at ~2-mo intervals. Following log transformations, number of foods, total energy, dietary fiber, and fat required only one measurement per household to achieve a correlation of 0.8 between the observed and true values. For percent energy from fat and energy density, 3 and 2 repeated measurements, respectively, were needed to achieve a correlation of 0.8. A sample size of 252 was needed to detect a difference of 25% of an SD in total energy with one measurement compared with 213 with 3 repeated measurements. Macronutrient characteristics of household foods appeared relatively stable over a 6-mo period and only 1 or 2 repeated measures of households may be sufficient for an efficient study design.

Body mass index at age 25 and all-cause mortality in whites and African Americans: the Atherosclerosis Risk in Communities study.

PURPOSE: Approximately 20% of young adults in the United States are obese, and most of them gain weight between young and middle adulthood. Few studies have examined the association between elevated body mass index (BMI) in early adulthood and mortality or have examined that such effects are independent of changes in weight. To our knowledge, no such study has been conducted in African-American samples. METHODS: We used data from 13,941 African-American and white adults who self-reported their weight at the age of 25, and had weight and height measured when they were 45-64 years of age (1987-1989). Date of death was ascertained between 1987 and 2005. Hazard ratios and hazard differences for the effects of BMI at age 25 on all-cause mortality were determined using Cox proportional hazard and additive hazard models, respectively. RESULTS: In the combined ethnic-gender groups, the hazard ratio associated with a 5 kg/m(2) increase in BMI at age 25 was 1.28 (95% confidence interval [CI]: 1.22-1.35), and the hazard difference was 2.75 (2.01-3.50) deaths/1,000 person-years. Associations were observed in all four ethnic-gender groups. Models including weight change from age 25 to age in 1987-1989 resulted in null estimates for BMI in African-American men, whereas associations were maintained or only mildly attenuated in other ethnic-gender groups. CONCLUSIONS: Excess weight during young adulthood should be avoided because it contributes to increases in death rates that may be independent of changes in weight experienced in later life. Further study is needed to better understand these associations in African-American men.

Are measures of height and leg length related to incident diabetes mellitus? The ARIC (Atherosclerosis Risk in Communities) study.

This study was designed to estimate the risk of developing diabetes in relation to adult height components, namely leg length and leg length/height ratio. Data on 12,800 individuals without diabetes were obtained at the baseline examination from the ARIC cohort. Cox proportional hazard models were used to estimate hazard rate ratios of diabetes for each 5-cm difference in leg length and 1 SD difference in the leg length/height ratio. During a mean follow-up period of 7.6 years, the age-adjusted incidence per 1,000 person years of follow-up was 25.8, 24.2, 10.4, and 16.2 in African American (AA) women, AA men, white women, and white men, respectively. The hazard ratio for diabetes (95% CI) per 5-cm difference in leg length was 0.85 (0.75-0.95) in white men, 0.79 (0.69-0.90) in white women, 0.90 (0.75-1.07) in AA women, and 0.99 (0.77-1.27) in AA men, after adjusting for age, parental history of diabetes, parental socioeconomic status, and weight at age 25. The hazard ratio for diabetes per 1 SD difference in leg length/height ratio followed the same trend. Leg length is inversely and independently related to an increased risk of diabetes in middle-age white men and women but not in African-Americans. This sex-race heterogeneity suggests that nutritional and environmental factors in childhood may modify this risk through different pathways.

Interim data monitoring to enroll higher-risk participants in HIV prevention trials.

BACKGROUND: Lower-than-expected incidence of HIV undermines sample size calculations and compromises the power of a HIV prevention trial. We evaluated the effectiveness of interim monitoring of HIV infection rates and on-going modification of recruitment strategies to enroll women at higher risk of HIV in the Cellulose Sulfate Phase III study in Nigeria. METHODS: We analyzed prevalence and incidence of HIV and other sexually transmitted infections, demographic and sexual behavior characteristics aggregated over the treatment groups on a quarterly basis. The site investigators were advised on their recruitment strategies based on the findings of the interim analyses. RESULTS: A total of 3619 women were screened and 1644 enrolled at the Ikeja and Apapa clinics in Lagos, and at the Central and Peripheral clinics in Port Harcourt. Twelve months after study initiation, the overall incidence of HIV was less than one-third of the pre-study assumption, with rates of HIV that varied substantially between clinics. Due to the low prevalence and incidence rates of HIV, it was decided to close the Ikeja clinic in Lagos and to find new catchment areas in Port Harcourt. This strategy was associated with an almost two-fold increase in observed HIV incidence during the second year of the study. CONCLUSION: Given the difficulties in estimating HIV incidence, a close monitoring of HIV prevalence and incidence rates during a trial is warranted. The on-going modification of recruitment strategies based on the regular analysis of HIV rates appeared to be an efficient method for targeting populations at greatest risk of HIV infection and increasing study power in the Nigeria trial. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov registry under #NCT00120770 http://clinicaltrials.gov/ct2/show/NCT00120770.

Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria.

BACKGROUND: This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection. METHODS: This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1:1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events. RESULTS: The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3-1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5-1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported. CONCLUSIONS: Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120770.

The changing risk factor profile of participants enrolled in a secondary stroke prevention trial: Vitamin intervention for stroke prevention.

OBJECTIVE: To determine if the stroke risk factor profile of participants in a large, multicenter secondary stroke prevention trial changed over the recruitment period. METHODS: The 3,680 participants in the Vitamin Intervention for Stroke Prevention (VISP) were categorized into four groups by enrollment date. Baseline patient characteristics and stroke risk factors were compared across groups. RESULTS: Hypertension and hypercholesterolemia management improved but prevalence of three major stroke risk factors did not change. Patients enrolled later had better Mini-Mental State and lower NIH Stroke Scale scores, higher multivitamin use, lower prevalence of cortical infarctions, cardiac symptoms and prior stroke, and lower serum creatinine levels. CONCLUSIONS: Those participants enrolled in the later recruitment periods had a different risk factor profile and risk factors were managed differently compared to those enrolled earlier.

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

CONTEXT: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. OBJECTIVE: To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. DESIGN: Double-blind randomized controlled trial (September 1996-May 2003). SETTING AND PARTICIPANTS: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. INTERVENTIONS: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid. MAIN OUTCOME MEASURES: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). RESULTS: Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. CONCLUSIONS: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Analysis of chirped-sampled and sampled-chirped fiber Bragg gratings.

We analyze sampled fiber Bragg gratings that have chirp in the grating period, in the sampling function, or in both. In the last-named case the sampling period can be chirped, the sample length can be chirped, or both. We explain the features in the spectral and group-delay (dispersion) responses for gratings that have a single chirp parameter. We then show how the response of sampled gratings that have multiple chirp parameters can be explained in terms of the single-chirp parameter cases.