Survival of propionic acidemia patients with liver transplant.

Propionic acidemia (PA) is a rare metabolic disorder affecting amino acid metabolism. Liver transplantation improves some outcomes, but the impact on long-term survival remains unclear. A systematic literature review and survival analysis, identifying 94 PA patients who underwent transplantation, revealed a survival probability of 62% at age 33; while median survival was estimated at 40 years. These findings highlight a substantial survival deficit of PA patients compared to the general population despite liver transplantation.

A systematic review of real-world evidence (RWE) supportive of new drug and biologic license application approvals in rare diseases.

BACKGROUND: Real-world evidence (RWE) generated using real-world data (RWD) presents the potential to contextualize and/or supplement traditional clinical trials for regulatory approval of rare diseases (RDs). This systematic review evaluated the use of RWD for non-oncologic RD therapies with orphan drug designation (ODD) to support efficacy outcomes in regulatory application packages to the US Food and Drug Administration (FDA). New drug applications (NDAs) and biologic license applications (BLAs) submitted between January 2017 and October 2022 were obtained from publicly available FDA drug approval websites. NDAs and BLAs of non-oncologic RD therapies were screened, and manually reviewed using RWE-related keywords. Quantitative summary of number/proportion of study types was provided, whereas qualitative synthesis focused on key categories of output assessing the use of RWD in overall drug approval process, including agency's feedback on its strengths and key challenges. RESULTS: A total of 868 NDAs and BLAs were identified, of which 243 were screened for non-oncologic RDs with ODD, and 151 were subsequently reviewed for the RWD used to support efficacy outcomes. Twenty (12 NDAs, 8 BLAs) applications met the review inclusion criteria. Most (19; 95%) applications used only retrospective RWD, while one (5%) collected RWD both retrospectively and prospectively. RWD studies included natural history including registry-based/retrospective historical controls (14; 70%), retrospective medical chart-reviews (4; 20%), and external RWD controls from other studies (2; 10%). The FDA generally accepted RWD studies demonstrating a large effect size despite the noted concerns and criticisms. However, the agency expressed concerns about overall quality and comparability of RWD with trial data for some applications, including RWD study designs with respect to differences in patients' baseline characteristics, missing information, and potential bias and measurement errors. CONCLUSIONS: This systematic review highlights potential benefits of appropriately conducted RWE studies in RD, which can strengthen the clinical evidence for efficacy comparison and contextualization to support product approval efforts, particularly when a large magnitude of effect is observed for the new intervention. Nonetheless, quality and completeness of RWD and its comparability with trial data remain areas of concern that can serve as valuable learnings for advancing future science and regulatory approvals.

An Evaluation of the Effect of the OxyContin Reformulation on Unintentional Fatal and Nonfatal Overdose.

OBJECTIVES: OxyContin was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin's reformulation on overdose (OD) risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care. MATERIALS AND METHODS: Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (extended release morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation changes in OD rates for OxyContin versus comparators. RESULTS: A total of 297,836 individuals were dispensed OxyContin and 659,673 individuals were dispensed a primary comparator across the 3 databases. Overall, there was little or no difference in the temporal change in OD incidence in comparators versus OxyContin (Medicaid: adjusted ratio-of-rate-ratios (aRoRs) ranging from 0.90 to 1.05; MarketScan/HIRD: aRoR ranging from 1.10 to 1.22). However, restriction to person-time without concomitant opioid use revealed a modestly greater reduction in OD incidence over time during OxyContin use, as the aRoRs comparing the primary comparators to OxyContin ranged from 1.06 to 1.30 in Medicaid and from 1.64 to 1.85 in MarketScan/HIRD. DISCUSSION: This study did not detect an overall effect of the OxyContin reformulation on OD in insured patients under regular medical care. There is a suggestion of a modestly reduced OxyContin-associated OD risk following the reformulation but only in commercially insured individuals receiving single-opioid regimens.

High-dose prescribed opioids are associated with increased risk of heroin use among United States military veterans.

Despite evidence linking increased risk of opioid use disorder with specific opioid-prescribing patterns, the relationship between these patterns and heroin use is less understood. This study aimed to determine whether dose and duration of opioid prescriptions predict subsequent heroin use in United States veterans. We analyzed data from 2002 to 2012 from the Veterans Aging Cohort Study, a prospective cohort study. We used inverse probability of censoring weighted Cox regression to examine the relationship between self-reported past year heroin use and 2 primary predictors: (1) prior receipt of a high-dose opioid prescription (≥90 mg morphine equivalent daily dose), and (2) prior receipt of a long-term opioid prescription (≥90 days). Heroin use was ascertained using most recent value of time-updated self-reported past year heroin use. Models were adjusted for HIV and hepatitis C virus infection status, sociodemographics, pain interference, posttraumatic stress disorder, depression, and use of marijuana, cocaine, methamphetamines, and unhealthy alcohol use. In the final model, prior receipt of a high-dose opioid prescription was associated with past year heroin use (adjusted hazard ratio use = 2.54, 95% confidence interval: 1.26-5.10), whereas long-term opioid receipt was not (adjusted hazard ratio = 1.09, 95% confidence interval: 0.75-1.57). Patients receiving high-dose opioid prescriptions should be monitored for heroin use. These findings support current national guidelines recommending against prescribing high-dose opioids for treating pain.

Residential mobility of pregnant women and implications for assessment of spatially-varying environmental exposures.

Health studies on spatially-varying exposures (e.g., air pollution) during pregnancy often estimate exposure using residence at birth, disregarding residential mobility. We investigated moving patterns in pregnant women (n = 10,116) in linked cohorts focused on Connecticut and Massachusetts, U.S., 1988-2008. Moving patterns were assessed by race/ethnicity, age, marital status, education, working status, population density, parity, income, and season of birth. In this population, 11.6% of women moved during pregnancy. Movers were more likely to be younger, unmarried, and living in urban areas with no previous children. Among movers, multiple moves were more likely for racial/ethnic minority, younger, less educated, unmarried, and lower income women. Most moves occurred later in pregnancy, with 87.4% of first moves in the second or third trimester, although not all cohort subjects enrolled in the first few weeks of pregnancy. Distance between first and second residence had a median value of 5.2 km (interquartile range 11.3 km, average 57.8 km, range 0.0-4277 km). Women moving larger distances were more likely to be white, older, married, and work during pregnancy. Findings indicate that residential mobility may impact studies of spatially-varying exposure during pregnancy and health and that subpopulations vary in probability of moving, and timing and distance of moves.

Facility and State Variation in Hip Fracture in U.S. Nursing Home Residents.

OBJECTIVES: To quantify the variation in hip fracture incidence across U.S. nursing home (NH) facilities and states and examine how hip fracture incidence varies according to facility- and state-level characteristics. DESIGN: Retrospective cohort using linked national Minimum Data Set assessments; Online Survey, Certification and Reporting records; and Medicare claims. SETTING: U.S. NHs with 100 or more beds. PARTICIPANTS: Long-stay NH residents between May 1, 2007, and April 30, 2008, from 1,481 facilities and 46 U.S. states (N = 201,892). MEASUREMENTS: Incident hip fractures were ascertained using Medicare Part A diagnostic codes. Each resident was followed for up to 2 years. RESULTS: The mean adjusted incidence rate of hip fractures for all facilities was 3.13 (95% confidence interval (CI) = 3.01-3.26) per 100 person-years (range 1.20, 95% CI = 1.15-1.26 to 6.40, 95% CI = 6.07-6.77). Facilities with the highest rates of hip fracture had greater percentages of residents taking psychoactive medications (top tertile 27.2%, bottom tertile 24.8%), and fewer nursing (top tertile 3.43, bottom tertile 3.53) and direct care (top tertile 3.22, bottom tertile 3.29) hours per day per resident. The combination of state and facility characteristics explained 6.7% of the variation in hip fracture, and resident characteristics explained 7.6%. CONCLUSION: Much of the variation in hip fracture incidence remained unexplained, although these findings indicate that potentially modifiable state and facility characteristics such as psychoactive drug prescribing and minimum staffing requirements could be addressed to help reduce the rate of hip fracture in U.S. NHs.

Fracture Risk Assessment in Long-term Care (FRAiL): Development and Validation of a Prediction Model.

Background: Strategies used to predict fracture in community-dwellers may not be useful in the nursing home (NH). Our objective was to develop and validate a model (Fracture Risk Assessment in Long-term Care [FRAiL]) to predict the 2-year risk of hip fracture in NH residents using readily available clinical characteristics. Methods: The derivation cohort consisted of 419,668 residents between May 1, 2007 and April 30, 2008 in fee-for service Medicare. Hip fractures were identified using Part A diagnostic codes. Resident characteristics were obtained using the Minimum Data Set and Part D claims. Multivariable competing risk regression was used to model 2-year risk of hip fracture. We validated the model in a remaining 1/3 sample (n = 209,834) and in a separate cohort in 2011 (n = 858,636). Results: Mean age was 84 years (range 65-113 years) and 74.5% were female. During 1.8 years mean follow-up, 14,553 residents (3.5%) experienced a hip fracture. Fifteen characteristics in the final model were associated with an increased risk of hip fracture including dementia severity, ability to transfer and walk independently, prior falls, wandering, and diabetes. In the derivation sample, the concordance index was 0.69 in men and 0.71 in women. Calibration was excellent. Results were similar in the internal and external validation samples. Conclusions: The FRAiL model was developed specifically to identify NH residents at greatest risk for hip fracture, and it identifies a different pattern of risk factors compared with community models. This practical model could be used to screen NH residents for fracture risk and to target intervention strategies.

Influenza Illness and Hip Fracture Hospitalizations in Nursing Home Residents: Are They Related?

Background: Influenza illness may impact the risk of falls and fractures during acute illness due to unsteady gait or dizziness. We evaluated the association between influenza and hip fracture hospitalizations in long-stay (LS) nursing home (NH) residents. Methods: We analyzed weekly rates of hospitalization in a retrospective cohort of LS NH residents between January 1, 2000 to December 31, 2009. Hip fracture and influenza like illness (ILI) hospitalizations were identified with Medicare fee-for-service part A claims. We evaluated unadjusted and adjusted models with the primary exposures, weekly rate of influenza-like illness hospitalizations, city-wide mortality, and NH influenza vaccination rate and primary outcome of weekly rate of hip fracture hospitalizations. Results: There were 9,237 incident hip fractures in the cohort. Facility wide ILI hospitalization rate was associated with the hip fracture hospitalization rate in the unadjusted (incidence rate ratio [IRR] 1.13, 95% confidence interval [CI]: 1.08, 1.17) and adjusted (IRR 1.13, 95% CI: 1.09, 1.18) analyses. City-wide influenza mortality was associated with hip fracture hospitalization rates for the unadjusted (IRR 1.03, 95% CI: 1.02, 1.04), and adjusted (IRR 1.02, 95% CI: 1.01, 1.03) analyses. NH influenza vaccination rates were not associated with changes in hip fracture hospitalization rates. Conclusions: ILI hospitalizations are associated with a 13% average increase in hip fracture hospitalization risk. In a given NH week, an increase in the number ILI hospitalizations from none to two was associated with an approximate one percentage point increase in hip fracture hospitalization risk. Strategies to reduce influenza risk should be investigated to reduce hip fracture risk.

Non-medical use of prescription opioids is associated with heroin initiation among US veterans: a prospective cohort study.

AIMS: To estimate the influence of non-medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care. DESIGN: Using a multivariable Cox regression model, we analyzed data from a prospective, multi-site, observational study of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self-reported measures of NMUPO and heroin use. SETTING: Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC. PARTICIPANTS: A total of 3396 HIV-infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life-time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012. MEASUREMENTS: The primary outcome measure was self-reported incident heroin use and the primary exposure of interest was new-onset NMUPO. Our final model was adjusted for socio-demographics, pain interference, prior diagnoses of post-traumatic stress disorder and/or depression and self-reported other substance use. FINDINGS: Using a multivariable Cox regression model, we found that non-medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation [adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35]. CONCLUSIONS: New-onset non-medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV-infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use.

Geographic Variation in Hip Fracture Among United States Long-Stay Nursing Home Residents.

INTRODUCTION: Despite high rates of hip fracture among United States (US) nursing home (NH) residents, little is known about geographic variation in hip fracture incidence. We used nationally representative data to identify geographic variation in hip fracture among US NH residents. DESIGN AND SETTING: Retrospective cohort study using Part A claims for a 100% of Medicare enrollees in 15,289 NHs linked to NH minimum data set and Online Survey, Certification, and Reporting databases. PARTICIPANTS: A total of 891,085 long-stay (continuous residence of ≥100 days) NH residents ≥65 years old. MEASUREMENTS: Medicare Part A claims documenting a hip fracture. Mean incidence rates of hip fracture for long-stay NH residents were calculated for each state and US Census Division from 2007 to 2010. RESULTS: The age-, sex-, and race-adjusted incidence rate of hip fracture ranged from 1.49 hip fractures/100 person-years (Hawaii) to 3.60 hip fractures/100 person-years (New Mexico), with a mean of 2.38 (standard deviation 0.43) hip fractures/100 person-years. The mean incidence of hip fracture was 1.7-fold greater in the highest quintile than the lowest. CONCLUSIONS: We observed modest US state and regional variation in hip fracture incidence among long-stay NH residents. Future studies should assess whether state policies or NH characteristics explain the variation.

State-level and system-level opioid prescribing policies: The impact on provider practices and overdose deaths, a systematic review.

OBJECTIVE: In response to persistent public health concerns regarding prescription opioids, many states and healthcare systems have implemented legislation and policies intended to regulate or guide opioid prescribing. The overall impact of these policies is still uncertain. The aim of this systematic review was to examine the existing evidence of provider-level and patient-level outcomes preimplementation and postimplementation of policies and legislation constructed to impact provider prescribing practices around opioid analgesics. DESIGN: A systematic search of MEDLINE, EMBASE, the Web of Science, and the Cochrane Database of Systematic Reviews was conducted to identify studies evaluating the impact of opioid prescribing policies on provider-level and patient-level outcomes. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eleven studies were included in the review. A meta-analysis was not possible due to between-study heterogeneity. Six of the studies assessed state-level policies, and five were at the level of the healthcare system or hospital. Studies showed temporal associations between policy implementation and reductions in opioid prescribing, as well as opioid-related overdoses. Results were mixed regarding the impact of policies on misuse. The majority of the studies were judged to be of low quality based on the GRADE criteria. CONCLUSIONS: There is low to moderate quality evidence suggesting that the presence of opioid prescribing policy will reduce the amount and strength of opioid prescribed. The presence of these policies may impact the number of overdoses, but there is no clear evidence to suggest that it reduces opioid misuse.

Routine HIV Screening in an Urban Community Health Center: Results from a Geographically Focused Implementation Science Program.

OBJECTIVE: CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. METHODS: Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. RESULTS: A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routine screening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. CONCLUSION: Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routine screening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection.

HIV and syphilis infection among men attending a [corrected] sexually transmitted infection clinic in Puerto Rico.

OBJECTIVE: This study aimed to assess the demographic, behavioral, and clinical factors associated with HIV and syphilis infection among a sample of men attending a sexually transmitted infection clinic during 2009 to 2010 in San Juan, Puerto Rico (PR). METHODS: A sample of 350 clinical records from men visiting the clinic for the first time during 2009 to 2010 was reviewed. Descriptive statistics were used to describe the study sample, and bivariate analyses were performed separately for HIV and syphilis to identify factors associated with these infectious diseases. Variables that were significantly associated (p < 0.05) with HIV and syphilis in the bivariate analysis were considered for inclusion in the logistic regression models. RESULTS: Overall, 11.2% and 14.1% of the men were infected with HIV and syphilis, respectively, and 5.1% were coinfected with HIV and syphilis. In multivariate logistic regression models, ever injecting drugs (POR = 8.1; 95% CI 3.0, 21.8) and being a man who has sex with men (MSM) (POR = 5.3; 95% CI 2.3, 11.9) were positively associated with HIV infection. Being a man older than 45 years (POR = 4.0; 95% CI: 1.9, 8.9) and being an MSM (POR = 2.5; 95% CI: 1.3, 4.9) were both significantly associated with syphilis infection. CONCLUSION: These findings reinforce the need for greater education and prevention efforts for HIV and other STIs among men in PR, particularly those who are MSM. However, there is a need to make an a priori assessment of the level of health literacy in the members of this group so that a culturally sensitive intervention can be provided to the men who attend this STI clinic.

Behavioral correlates of fruit and vegetable intake in Puerto Rico: results from the Health Information National Trends Survey.

OBJECTIVE: A diet high in fruit and vegetables (FV) is associated with a decreased risk for chronic diseases, such as cancer. Limited information exists regarding the factors associated with FV intake in persons living in Puerto Rico. The objective of this study was to examine sociodemographic, behavioral, and health-belief factors associated with dietary habits in Puerto Rico. METHODS: Secondary data analysis of adults aged 18 years and older from the Puerto Rico Health Information National Trends Survey (HINTS-PR) conducted in 2009. Multivariate logistic regression models were used to identify factors associated with meeting the established recommendations for FV consumption. RESULTS: Only 14.5% of the adults in Puerto Rico met the recommendations for daily FV intake, and the vast majority (90.9%) were unaware of current recommendations. Bivariate analyses demonstrated that being obese, having lower than a high school education, and not knowing the recommendations were significantly associated with not meeting these recommendations. In the multivariate logistic regression analysis, being obese (OR = 3.77; 95% CI = 1.41-10.08) and not being aware of the current dietary recommendations (OR = 9.26; 95% CI = 3.77-22.73) continued to be significantly associated with not meeting the FV intake recommendations. CONCLUSION: The Puerto Rican population is far from meeting FV consumption recommendations, with prevalence estimates of consumption that are below the US median. Low FV intake might put the population in Puerto Rico at increased risk of developing cancer as well as a number of other chronic diseases that are secondary both to improper nutrition and to obesity.