[Show abstract][Hide abstract] ABSTRACT: We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett's esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association.
Osteoporosis International 10/2014; 26(2). DOI:10.1007/s00198-014-2925-9 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Prescription opioid use and overdose deaths are increasing in the United States. Among disabled Medicare beneficiaries under the age of 65, the rise in musculoskeletal conditions as qualifying diagnoses suggests that opioid analgesic use may be common and increasing, raising safety concerns.
From a 40% random-sample Medicare denominator, we identified fee-for-service beneficiaries under the age of 65 and created annual enrollment cohorts from 2007 to 2011 (6.4 million person-years). We obtained adjusted, annual opioid use measures: any use, chronic use (≥ 6 prescriptions), intensity of use [daily morphine equivalent dose (MED)], and opioid prescribers per user. Geographic variation was studied across Hospital Referral Regions.
Most measures peaked in 2010. The adjusted proportion with any opioid use was 43.9% in 2007, 44.7% in 2010, and 43.7% in 2011. The proportion with chronic use rose from 21.4% in 2007 to 23.1% in 2011. Among chronic users: mean MED peaked at 81.3 mg in 2010, declining to 77.4 mg in 2011; in 2011, 19.8% received ≥ 100 mg MED; 10.4% received ≥ 200 mg. In 2011, Hospital Referral Region-level measures varied broadly (5th-95th percentile): any use: 33.0%-58.6%, chronic use: 13.9%-36.6%; among chronic users, mean MED: 45 mg-125 mg; mean annual opioid prescribers: 2.4-3.7.
Among these beneficiaries, opioid use was common. Although intensity stabilized, the population using opioids chronically grew. Variation shows a lack of a standardized approach and reveals regions with mean MED at levels associated with overdose risk. Future work should assess outcomes, chronic use predictors, and policies balancing pain control and safety.
Medical Care 09/2014; 52(9):852-9. DOI:10.1097/MLR.0000000000000183 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess uptake of postfracture care guidelines in community-dwelling Medicare recipients with fractures.
Retrospective observational cohort study.
Claims-based study using U.S. Medicare administrative inpatient, outpatient (2003-2010), and prescription (2006-2010) data.
Individuals aged 68 and older who survived at least 12 months after a fracture of the hip, radius, or humerus.
Poisson regression modeled factors, including participant characteristics, comorbidities and hospital referral region (HRR), associated with bone density testing or osteoporosis pharmacotherapy in the 6 months after fracture. Models were repeated for participants with no osteoporosis care observed before fracture (attention naïve).
In 61,832 individuals with fractures, mean age was 80.6, 87.0% were female, 88.5% were white, 2.6% were black, and 62.1% were attention naïve at the time of fracture; 21.8% received testing, pharmacotherapy, or both in the 6 months after fracture. In adjusted models, factors associated with significantly lower likelihood of receiving this care were black race, male sex, and an upper extremity fracture (vs hip). In models restricted to attention-naïve participants, the same factors were associated with lower relative risk of receiving care. Adjusted HRR-level care rates ranged from 14.7% to 22.9% (10th to 90th percentile). The proportion receiving care increased from 2006 to 2009.
Postfracture osteoporosis care was uncommon, particularly in black and male participants. Care increased over time, but for most, a fracture was insufficient to trigger effective secondary prevention, especially for participants who were not receiving prefracture osteoporosis attention. Clinicians and policy-makers must consider effective remedies to this persistent care gap.
Journal of the American Geriatrics Society 11/2013; 61(11):1855-62. DOI:10.1111/jgs.12507 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the impact of a parent-coaching intervention based on the Early Start Denver Model (P-ESDM) on parenting-related stress and sense of competence. This was part of a multisite, randomized trial comparing P-ESDM (n = 49) with community intervention (n = 49) for children aged 12 and 24 months. The P-ESDM group reported no increase in parenting stress, whereas the Community group experienced an increase over the same 3-month period. Parental sense of competence did not differ. Number of negative life events was a significant predictor of parenting stress and sense of competence across both groups. This suggests that a parent-coaching intervention may help maintain parental adjustment directly after a child is diagnosed with ASD.
Journal of Autism and Developmental Disorders 07/2013; 44(2). DOI:10.1007/s10803-013-1874-z · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism Spectrum Disorder (ASD) is a developmental disability that affects social behavior and language acquisition. ASD exhibits great variability in outcomes, with some individuals remaining nonverbal and others exhibiting average or above average function. Cognitive ability contributes to heterogeneity in autism and serves as a modest predictor of later function. We show that a brain measure (event-related potentials, ERPs) of word processing in children with ASD, assessed at the age of 2 years (N = 24), is a broad and robust predictor of receptive language, cognitive ability, and adaptive behavior at ages 4 and 6 years, regardless of the form of intensive clinical treatment during the intervening years. The predictive strength of this brain measure increases over time, and exceeds the predictive strength of a measure of cognitive ability, used here for comparison. These findings have theoretical implications and may eventually lead to neural measures that allow early prediction of developmental outcomes as well as more individually tailored clinical interventions, with the potential for greater effectiveness in treating children with ASD.
PLoS ONE 05/2013; 8(5):e64967. DOI:10.1371/journal.pone.0064967 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:Parents of children with autism spectrum disorders (ASDs) are at risk for higher stress levels than parents of children with other developmental disabilities and typical development. Recent advances in early diagnosis have resulted in younger children being diagnosed with ASDs but factors associated with parent stress in this age group are not well understood. Aims: The present study examined parenting-related stress and psychological distress in mothers of toddlers with ASD, developmental delay without ASD (DD), and typical development. The impact of child problem behavior and daily living skills on parenting-stress and psychological distress were further investigated. Methods: Participants were part of a larger research study on early ASD intervention. Results: Parent self-report of parenting-related stress and psychological distress was utilized. Parents of toddlers with ASD demonstrated increased parenting-related stress compared with parents of toddlers with DD and typical development. However, psychological distress did not differ significantly between the groups. Child behavior problems, but not daily living skills emerged as a significant predictor of parenting-related stress and psychological distress. This was true for both mothers of children with ASD and DD. Conclusions: These finding suggest that parents' abilities to manage and reduce behavior problems is a critical target for interventions for young children with ASD and DD in order to improve child functioning and decrease parenting-related stress.
Brain & development 11/2012; 35(2). DOI:10.1016/j.braindev.2012.10.004 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The 62 lung transplant centers in the United States are unevenly distributed. We examined whether remote dwelling (distance from one's primary residence to the nearest lung transplant center) or rural dwelling (as opposed to urban) influences patients' access to lung transplantation, and whether such relationships changed following introduction of the lung allocation score (LAS) in May 2005. Between July 2001 and February 2009, 14 015 patients were listed for lung transplantation and 7923 (56.5%) were transplanted. Americans lived a median of 90.3 miles (IQR: 45.3-159.4) from the closest transplant center. Distance from a lung transplant center was inversely associated with the hazard of being listed before LAS implementation (adjusted HR for 100 miles = 0.87 [0.83-0.90]) and afterward (0.81 [0.78-0.85]); LAS implementation did not modify this relationship (p = 0.38). Once waitlisted, distance from the closest center was not associated with time to transplantation, and among those transplanted, distance was not associated with survival. Similar results were identified for rural, as opposed to urban, residence. We conclude that geographic disparaties exist in access to lung transplantation in the United States. These are mediated by listing practices rather than by transplantation rates, and were not mitigated by LAS implementation.
American Journal of Transplantation 08/2012; 12(11). DOI:10.1111/j.1600-6143.2012.04202.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme.
Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism.
Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score.
The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362,809 patients and 792,665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574,584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367,612 patients and 815,945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31).
Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy.
Pharmacoepidemiology and Drug Safety 05/2012; 21(5):494-506. DOI:10.1002/pds.3199 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities.
We conducted a retrospective cohort study of 13 749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30 days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs).
A new PPI prescription within 30 days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR = 1.21 for each additional condition, 95%CI = 1.13-1.28), recent hospitalization (OR = 4.71, 95%CI = 4.02-5.52), prednisone dose higher than 40 mg/day (OR = 1.87, 95%CI = 1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR = 1.54, 95%CI = 1.24-1.91), renal insufficiency (OR = 2.06, 95%CI = 1.73-2.46), and liver disease (OR = 1.82, 95%CI = 1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR = 1.89, 95%CI = 1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI = 4.4-8.2%).
Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids.
Pharmacoepidemiology and Drug Safety 04/2012; 21(4):366-74. DOI:10.1002/pds.2350 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aims to assess whether digoxin has a different effect on mortality risk for women than it does for men in patients with heart failure (HF).
This study uses the UK-based The Health Information Network population database in a cohort study of the impact of digoxin exposure on mortality for men and women who carry the diagnosis of HF. Digoxin exposure was assessed based on prescribing data. Multivariable Cox proportional hazards models were used to assess whether there was an interaction between sex and digoxin affecting mortality hazard.
The setting was primary care outpatient practices.
The study cohort consisted of 17 707 men and 19 227 women with the diagnosis of HF who contributed only time without digoxin exposure and 9487 men and 10 808 women with the diagnosis of HF who contributed time with digoxin exposure.
The main outcome measure was all-cause mortality.
The primary outcome of this study was the absence of a large interaction between digoxin use and sex affecting mortality. For men, digoxin use was associated with a HR for mortality of 1.00, while for women, the HR was also 1.00 (p value for interaction 0.65). The results of sensitivity analyses were consistent with those of the primary analysis.
Observational data do not support the concern that there is a substantial increased risk of mortality due to the use of digoxin in women. This finding is consistent with previous observational studies but discordant with results from a post hoc analysis of a randomised controlled trial of digoxin versus placebo.
BMJ Open 03/2012; 2(2):e000888. DOI:10.1136/bmjopen-2012-000888 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bilateral lung transplantation (BLT) improves survival compared with single lung transplantation (SLT) for some individuals with chronic obstructive pulmonary disease (COPD). However, it is unclear which strategy optimally uses this scarce societal resource.
To compare the effect of SLT versus BLT strategies for COPD on waitlist outcomes among the broader population of patients listed for lung transplantation.
We developed a Markov model to simulate the transplant waitlist using transplant registry data to define waitlist size, donor frequency, the risk of death awaiting transplant, and disease- and procedure-specific post-transplant survival. We then applied this model to 1,000 simulated patients and compared the number of patients under each strategy who received a transplant, the number who died before transplantation, and total post-transplant survival.
Under baseline assumptions, the SLT strategy resulted in more patients transplanted (809 vs. 758) and fewer waitlist deaths (157 vs. 199). The strategies produced similar total post-transplant survival (SLT = 4,586 yr vs. BLT = 4,577 yr). In sensitivity analyses, SLT always maximized the number of patients transplanted. The strategy that maximized post-transplant survival depended on the relative survival benefit of BLT versus SLT among patients with COPD, donor interval, and waitlist size.
In most circumstances, a policy of SLT for COPD improves access to organs for other potential recipients without significant reductions in total post-transplant survival. However, there may be substantial geographic variations in the effect of such a policy on the balance between these outcomes.
American Journal of Respiratory and Critical Care Medicine 08/2011; 184(11):1282-8. DOI:10.1164/rccm.201104-0695OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism is a common neurodevelopmental disorder with a complex mode of inheritance. It is one of the most highly heritable of the complex disorders, although the underlying genetic factors remain largely unknown. Here, we report mutations in the X-chromosome PTCHD1 (patched-related) gene in seven families with autism spectrum disorder (ASD) and in three families with intellectual disability. A 167-kilobase microdeletion spanning exon 1 was found in two brothers, one with ASD and the other with a learning disability and ASD features; a 90-kilobase microdeletion spanning the entire gene was found in three males with intellectual disability in a second family. In 900 probands with ASD and 208 male probands with intellectual disability, we identified seven different missense changes (in eight male probands) that were inherited from unaffected mothers and not found in controls. Two of the ASD individuals with missense changes also carried a de novo deletion at another ASD susceptibility locus (DPYD and DPP6), suggesting complex genetic contributions. In additional males with ASD, we identified deletions in the 5' flanking region of PTCHD1 that disrupted a complex noncoding RNA and potential regulatory elements; equivalent changes were not found in male control individuals. Thus, our systematic screen of PTCHD1 and its 5' flanking regions suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.
Science translational medicine 09/2010; 2(49):49ra68. DOI:10.1126/scitranslmed.3001267 · 15.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Idiopathic pulmonary fibrosis (IPF) has not been shown to respond to corticosteroid therapy; however, many patients receive these drugs at the time of diagnosis. The factors that are associated with the decision to prescribe corticosteroids have not been examined.
We conducted a retrospective cohort study of 1126 patients with a new diagnosis of IPF using The Health Improvement Network (THIN) database from the United Kingdom. We used generalized estimating equation (GEE) regression models to test the association of patient characteristics, co-morbid diseases, and disease characteristics with the use of corticosteroids within 30 days of IPF diagnosis.
Bivariable analyses demonstrated an association between female sex, the presence of dyspnea, the need for oxygen, past steroid use, and the use of corticosteroids immediately prior to diagnosis with the use of corticosteroids at the time of diagnosis. After adjustment with multivariable GEE regression, only the use of oxygen at the time of diagnosis (OR 1.69, CI 1.14-2.49), the past use of corticosteroids (OR 1.50, CI 1.04-2.15), and use of corticosteroids immediately prior to diagnosis (OR 5.72, CI 3.80-8.60) remained significantly associated with the use of corticosteroids immediately following diagnosis. No association was found between prior diabetes, osteoporosis, glaucoma, hypertension, congestive heart failure, obesity, or peptic ulcer disease and use of corticosteroids at diagnosis.
The decision to prescribe corticosteroids is associated with oxygen use and past corticosteroid use but is not influenced by factors such as age, gender, or common co-morbid conditions that may pre-dispose patients to adverse events of therapy.
Pharmacoepidemiology and Drug Safety 07/2010; 19(7):756-62. DOI:10.1002/pds.1959 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIMS To assess the impact of specialty society guidelines on the use of corticosteroids and cytotoxic agents in the initial management of patients with idiopathic pulmonary fibrosis. METHODS A retrospective cohort study of 941 patients with an incident diagnosis of IPF was conducted using a large medical records database. The primary outcome was a new prescription for corticosteroids with or without a cytotoxic agent within 30 days of diagnosis. The primary exposure was whether diagnosis occurred before or after the publication of treatment guidelines. Logistic regression was used to control for changes in population demographics and disease characteristics across time. RESULTS In total, 187 patients (19.9%) received a new corticosteroid prescription within 30 days of diagnosis. Fewer patients received corticosteroids after the publication of guidelines (22.2% vs. 17.7%; adjusted OR for steroid use after the publication of guidelines 0.65, 95% confidence interval 0.46, 0.92, P = 0.014). Among the 187 patients treated with corticosteroids, 22 (11.8%) also received a cytotoxic agent. The use of cytotoxic agents among users of corticosteroids increased significantly after the publication of guidelines (5.1% vs. 19.3%) with a fully adjusted OR = 4.71 (95% CI 1.56, 14.21, P = 0.006). CONCLUSIONS Since the publication of treatment guidelines, there has been a small reduction in the overall use of corticosteroids. Consistent with these guidelines, the use of cytotoxic agents among those prescribed corticosteroids has increased significantly; however, the use of these agents remains uncommon.
British Journal of Clinical Pharmacology 07/2010; 70(1):118-25. DOI:10.1111/j.1365-2125.2010.03670.x · 3.88 Impact Factor