Lessons learned from CMS's National Partnership to Improve Dementia Care: a thematic synthesis of multiple stakeholder-engaged studies.

BACKGROUND: Antipsychotic prescribing in United States nursing homes (NHs) has decreased since the Center for Medicare & Medicaid Service debuted the National Partnership to Improve Dementia Care in Nursing Homes (NP); however, reductions have stalled. To help explain persistent antipsychotic use despite the NP's reduction efforts, the perspectives of diverse NP stakeholders were qualitatively assessed. This study aimed to re-evaluate these individual perspectives in combined thematic synthesis to discover NP improvement opportunities undetectable in single stakeholder assessments. METHODS: Thematic synthesis. Through immersive crystallisation, original source coding results were organised into related descriptive themes. Similarities and differences were identified, and descriptive themes were regrouped into new, increasingly abstract, analytical themes. This cycle continued until variances were resolved and analytic themes sufficiently described and explained all initial descriptive themes. RESULTS: Three analytic themes emerged regarding NP improvement opportunities. The NP's positive impacts would be augmented by: (i) a deeper and expanded appreciation of stakeholder perspectives; (ii) more urgent and rapid adaptation to unintended adverse outcomes; and (iii) greater recognition of the contextual and environmental factors influencing decisions to prescribe or not prescribe antipsychotic medications. Stakeholder groups described: perspectives they perceived as inadequately considered by the NP; insufficient NP engagement with the stakeholders capable of creating evidenced, affordable, and available non-pharmacologic therapies for dementia symptoms; recognition that dementia interventions effective for a specific individual at a specific time in a specific community may not generalise; and diverse ongoing undesirable outcomes from NP policies that could be mitigated by NP modifications. CONCLUSIONS: The NP has done much to advance dementia care in NHs. Notwithstanding, these results suggest the NP would only be improved through increasingly comprehensive inclusion of stakeholder perspectives, enhanced incorporation of individual contextual factors, and a more decisive mechanism for ongoing and continual adaptation.

Understanding Long-Stay Gabapentin Use Increases: A National Nursing Home Clinician Survey on Prescribing Intent.

OBJECTIVES: Explore the indications for long-stay gabapentin use and elucidate the factors spurring the rapid increase in gabapentin prescribing in nursing homes (NHs). METHODS: National cross-sectional survey of NH prescribers distributed anonymously using SurveyMonkey. Sampling for convenience was obtained through crowdsourcing, leveraging collaborations with NH clinician organizations. Developed by a multidisciplinary team, pilot data/existing literature informed survey content. RESULTS: A total of 131 surveys completed. Participants: 71% white, 52% female, 71% physicians. Off-label gabapentin prescribing was ubiquitous. Nearly every clinician used gabapentin for neuropathic pain, most for any form of pain. Many clinicians also prescribe gabapentin to moderate psychiatric symptoms and behaviors. Clinicians' prescribing was influenced by opioid, antipsychotic, and anxiolytic reduction policies because gabapentin was perceived as an unmonitored and safer alternative. CONCLUSIONS: Off-label gabapentin increases are closely linked to opioid reduction efforts as more NH clinicians utilize gabapentin as an unmonitored opioid alternative. Our results highlight, however, the less recognized significance of long-stay prescribing for psychiatric symptoms and the similar contribution of psychotropic reduction initiatives, a phenomenon warranting further scrutiny. CLINICAL IMPLICATIONS: Clinicians perceive gabapentin as safer than the drugs it is replacing. Whether this is true remains unclear; the individual- and population-level risks of increased gabapentin use are largely unknown.

Community, Social, and Facility Factors and Long-stay Antipsychotic Use.

OBJECTIVES: Compare Virginia nursing homes in the top- and bottom-quintiles of antipsychotic use for variation in community, social, and facility factors. METHODS: 2018 CMS data ascertained Virginia nursing homes in the top and bottom quintiles for antipsychotic use. The Virginia Health Department provided social determinant of health (SDOH) statistics for each facility's county/city while claims identified facility demographics. Chi square and independent two-sample t-tests compared quintiles for regional, social, and demographic differences. RESULTS: Quintiles averaged 3000 residents and 56 facilities. Facilities with the lowest rates of antipsychotic use were more likely to be privately owned and had fewer African-American and minority residents and more white residents. All 18 SDOH statistics were superior for the communities of facilities with the lowest antipsychotic rates. Nine of these differences were statistically significant, including the aggregated "Health Opportunity Index." CONCLUSIONS: The antipsychotic prevalence rate for facilities in the top-quintile of antipsychotic use is fivefold the bottom-quintile's rate. Antipsychotic prescribing in nursing homes is associated with regional, demographic, and social factors not addressed by existing antipsychotic reduction measures, with vulnerable populations at greatest risk. CLINICAL IMPLICATIONS: The efficacy of measures aimed at curbing long-stay antipsychotic prescribing could be improved by addressing SDOH including economic opportunities.

Unreported Antipsychotic Use Increasing in Nursing Homes: The Impact of Quality-Measure Exclusions on the Percentage of Long-Stay Residents Who Got an Antipsychotic Medication Quality-Measure.

OBJECTIVE: Excluded from reporting to CMS's Percentage of long-stay residents who got an antipsychotic medication quality-measure are antipsychotics prescribed to nursing home patients with schizophrenia, Tourette's, or Huntington's. Over the 4 years following its 2012 debut, the quality-measure calculated a 27% reduction in inappropriate antipsychotic use but also an 18.3% increase in exclusion claims. This study evaluated the impact of these exclusions on the measure's findings. METHODS: Claims data for the years 2011-2016 retrospectively identified the prevalence of schizophrenia, Tourette's, and Huntington's in quarterly cohorts of Virginia long-stay residents prescribed antipsychotics. Annualized diagnoses in 2011 were compared with subsequent years using simple logistic regression. RESULTS: In 2016, 29% of the antipsychotics prescribed in Virginia nursing homes were to residents with diagnoses of schizophrenia, Tourette's, and Huntington's, a significant 32% increase from 2011. CONCLUSION: Almost 30% of the antipsychotics employed in Virginia nursing homes are excluded from CMS's long-stay antipsychotic quality-measure.

Increased Reporting of Exclusionary Diagnoses Inflate Apparent Reductions in Long-Stay Antipsychotic Prescribing.

OBJECTIVE: Over the two years following the 2012 introduction of CMS's National Partnership, combined rates of schizophrenia, Tourette's, and Huntington's in US long-stay residents increased 12%. We evaluated trends in reporting of these diagnoses for the subgroup of long-stay residents on antipsychotics. METHODS: Retrospective analysis of Virginia Medicaid claims identified annual utilization rates of psychiatric diagnoses for long-stay seniors on antipsychotics. Chi-square analysis compared rates for the year before March, 2012 with the same 12-month period 1 year later. A 5-year pre-existing baseline rate was also obtained. RESULTS: Diagnosis rates for 2011 were unchanged from baseline. Comparing 2011 with 2013, diagnoses rates for schizophrenia, Tourette's, and Huntington's combined increased 40% (p < .0001), primarily because schizophrenia reporting nearly doubled (p < .0001). CONCLUSIONS: For long-stay seniors on antipsychotics, reporting of schizophrenia, Tourette's, and Huntington's began increasing in 2012 and at almost triple the rate CMS described for the general long-stay population. The increased reporting of these diagnoses described by CMS since 2012 appears to be new and concentrated in residents on antipsychotics Clinical Implications: Since antipsychotics prescribed for schizophrenia, Tourette's, and Huntington's are excluded from quality-measure auditing, apparent reductions in inappropriate long-stay antipsychotic use since the National Partnership may be exaggerated.

Understanding Pandemic Increases in Long-Stay Psychotropic Prescribing for Dementia Symptoms: A Survey of Nursing Home Clinicians.

Objective: To explore the perceptions of nursing home (NH) clinicians regarding factors underpinning known increases in psychotropic prescribing over the COVID-19 pandemic. Methods: Three iterative online surveys were fielded to Virginia NH prescribing clinicians (11/2021-6/2022) to assess their perspectives regarding factors driving pandemic increases in NH psychotropic use. Existing literature and emerging survey data informed survey content. Sampling was for convenience and achieved through crowdsourcing, leveraging collaborations with Virginia NH clinician professional organizations. Results: A total of 89 surveys were collected. Clinicians noted simultaneous surging of dementia symptoms with decreased availability of non-pharmacologic measures to remedy them, leading to increased prescribing of all psychotropics. Staff shortages and turnover, isolation from family and community, and personal protective equipment protocols were identified as key pandemic factors contributing to this mismatch. Conclusions: Virginia NH clinicians explicitly linked increased NH psychotropic prescribing to known pandemic phenomena, associations previously hypothesized, but not, to our knowledge, directly confirmed.

Quality Gap in Long-Stay Antipsychotic Quality Measure Performance Widens Over the Pandemic, Reversing Past Gains.

The Centers for Medicare & Medicaid Services (CMS) grades nursing home performance in antipsychotic prescribing quarterly, publishing findings as a quality measure. While scores have improved since 2011, marked performance variation between facilities persists. To assess quality gap changes between best- and worst-performing deciles, we compared quarterly prescribing changes between these groups pre-pandemic (April 2011 to March 2020) and during the pandemic (April 2020 to March 2022). Antipsychotic quality measure scores, improving pre-pandemic, deteriorated during the pandemic. The pre-pandemic quality gap between the best- and worst-performing deciles narrowed as the worst-performing decile improved faster than the best-performing decile. During the pandemic, the quality gap widened as the worst-performing decile relapsed more than the best-performing decile (p < .0001). The pandemic disrupted quality performance gains and compounded disparities between facilities. A better understanding of the factors allowing high performers to weather pandemic stressors better than poor performers may reveal opportunities to improve nursing home quality and equity for all residents.

Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

BACKGROUND: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. OBJECTIVE: Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. METHODS: To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. RESULTS: Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. CONCLUSIONS: This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64446.

Analysing malaria drug trials on a per-individual or per-clone basis: a comparison of methods.

There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment.

Trends in Antiseizure Medication Prescribing Among Nursing Home Residents With and Without a Seizure Diagnosis.

OBJECTIVES: Evaluate current prevalence and changes in prescribing of antiseizure medications (ASMs) in Virginia nursing homes for residents with and without seizures. METHODS: Retrospective cohort. De-identified claims extracted from the Virginia All-Payers-Claims-Database defined annual and biennial cohorts of all insured long-stay residents with and without any claims-based seizure diagnoses. ASM prescribing prevalence rates for these cohorts were analyzed from 2011 to 2016. Multiple logistic regression compared prescribing prevalence rates within and between these 2 groups. RESULTS: Annual cohorts averaged 57,190. 65.6% Female, 38% white. 80% public insurance, 20% commercial secondary. Between 2011 and 2016, the claims-based prevalence of seizure diagnoses decreased (17.1% to 10.5%). However, ASM prescribing prevalence increased (10.4% to 11.6%). Increases were entirely among residents who never had any seizure-epilepsy claim, whereas ASM prescribing among residents with seizures decreased. Different drugs were used for patients with and without seizures. For residents without seizures, 85% of ASMs prescribed have alternative indications for mood or pain symptoms, and large gains in gabapentin and modest but significant increases in valproate, lamotrigine, carbamazepine, and topiramate prescribing were detected. Among residents with seizures, ASMs without alternative indications were more common (59%), with marked reductions in phenobarbital and phenytoin but significant increases in levetiracetam and lacosamide use observed. CONCLUSIONS: Long-stay ASM use is changing. ASM gains are unrelated to seizure-epilepsy prevalence. ASM prescribing increased only among residents without seizures, where ASMs with expanded indications were preferred. Long-stay ASM prescribing and prescribing indication should be included in mandatory CMS reporting similar to other CNS-active medications.

Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.

Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients. VDAC1 is identified to interact with WFS1, whereas loss of this interaction in WS cells could compromise mitochondrial function. Restoring WFS1 levels in WS cells reinstates WFS1-VDAC1 interaction, which correlates with an increase in MAMs and mitochondrial network that could positively affect mitochondrial function. Genetic rescue by WFS1 overexpression or pharmacological agents modulating mitochondrial function improves the viability and bioenergetics of WS neurons. Our data implicate a role of WFS1 in regulating mitochondrial functionality and highlight a therapeutic intervention for WS and related rare diseases with mitochondrial defects.

Analysis of Mitochondrial Dysfunction by Microplate Reader in hiPSC-Derived Neuronal Cell Models of Neurodegenerative Disorders.

Mitochondria are responsible for many vital pathways governing cellular homeostasis, including cellular energy management, heme biosynthesis, lipid metabolism, cellular proliferation and differentiation, cell cycle regulation, and cellular viability. Electron transport and ADP phosphorylation coupled with proton pumping through the mitochondrial complexes contribute to the preservation of mitochondrial membrane potential (ΔΨm). Importantly, mitochondrial polarization is essential for reactive oxygen species (ROS) production and cytosolic calcium (Ca2+) handling. Thus, changes in mitochondrial oxidative phosphorylation (OXPHOS), ΔΨm, and ATP/ADP may occur in parallel or stimulate each other. Brain cells like neurons are heavily reliant on mitochondrial OXPHOS for its high-energy demands, and hence improper mitochondrial function is detrimental for neuronal survival. Indeed, several neurodegenerative disorders are associated with mitochondrial dysfunction. Modeling this disease-relevant phenotype in neuronal cells differentiated from patient-derived human induced pluripotent stem cells (hiPSCs) provide an appropriate cellular platform for studying the disease pathology and drug discovery. In this review, we describe high-throughput analysis of crucial parameters related to mitochondrial function in hiPSC-derived neurons. These methodologies include measurement of ΔΨm, intracellular Ca2+, oxidative stress, and ATP/ADP levels using fluorescence probes via a microplate reader. Benefits of such an approach include analysis of mitochondrial parameters on a large population of cells, simultaneous analysis of different cell lines and experimental conditions, and for drug screening to identify compounds restoring mitochondrial function.

Development, evaluation, and application of an in silico model for antimalarial drug treatment and failure.

Pharmacological mechanism-based modeling was refined and used to develop an in silico model of antimalarial drug treatment validated against clinical and field data. We used this approach to investigate key features of antimalarial drug action and effectiveness, with emphasis on the current generation of artemisinin combination therapies. We made the following conclusions. (i) The development of artemisinin tolerance and resistance will, unless checked, have an immediate, large impact on the protection afforded to its partner drug and on the likely clinical efficacy of artemisinin combination therapies. (ii) Long follow-up periods are required in clinical trials to detect all drug failures; the follow-up periods of 28 days recommended by the World Health Organization are likely to miss at least 50% of drug failures, and we confirmed recent suggestions that 63 days would be a more appropriate follow-up period. (iii) Day 7 serum drug concentrations are a significant risk factor of failure, although, paradoxically, receiver operating characteristic curve analysis revealed that their predictive power is relatively poor. (iv) The pharmacokinetic properties of the partner drugs in artemisinin-containing combination therapies are the most important determinants of treatment outcome, particularly the maximum killing rate. We discuss the assumptions made in such modeling approaches and how similar approaches may be refined in future work.

Lack of choice in caregiving decision and caregiver risk of stress, North Carolina, 2005.

INTRODUCTION: An aspect of caregiving that has received little attention is the degree to which the choice to provide care affects a caregiver's emotional well-being. We compared a population-based sample of informal caregivers who reported having a choice in caring with caregivers who did not have a choice in caring to determine the extent to which choice affects caregivers' self-reported stress. METHODS: We identified 341 informal caregivers who completed a caregiving module appended to the 2005 North Carolina Behavioral Risk Factor Surveillance System survey. We determined participants' self-reported stress by using a 5-point scale that was dichotomized and used adjusted binomial logistic regression to assess the risk of stress given lack of choice in caregiving. RESULTS: In the fully adjusted model, caregivers without a choice in caring were more than 3 times as likely to report stress as caregivers with a choice in caring. High level of burden also increased stress. Caregivers with no choice in caring were most commonly the primary caregiver of a parent. CONCLUSION: Caregivers who do not have a choice in caregiving were at increased risk of stress, which may predispose them to poor health outcomes. Further investigation is needed to determine whether interventions that target caregivers without a choice in caring can reduce their levels of stress.

A review of malocclusion among individuals with mental and physical disabilities.

Oral health disparities between individuals with disabilities and the general population are widely reported in the literature, and malocclusion is no exception. As the number of people living with disabilities grows, so does the need to explore their oral health status. This review examines the reported prevalence of malocclusion in individuals with Down syndrome (DS), cerebral palsy (CP), cleft disorders, mental disabilities, and physical disabilities from 1976 to 2004. Malocclusion was assessed according to Angle's classifications, the Dental Aesthetic Index (DAI), and selected occlusion characteristics. The prevalence of malocclusion was higher in individuals with disabilities than in controls without disabilities. Malocclusion was more frequent when the handicap was mental rather than physical in origin. Class II and Class III malocclusions were common in individuals with CP and DS, respectively. Crowding, anterior diastema, and >1/2 cusp antero-posterior molar relations were frequent among people with disabilities. Findings varied according to disability, but were attributed to musculoskeletal abnormalities, altered cranial-base relationships, premature tooth eruption, corrective surgery, and lip incompetence. Only a deep bite was more frequent in controls compared to the individuals with disabilities.

Caregiver Perspectives About Using Antipsychotics and Other Medications for Symptoms of Dementia.

Background and Objectives: To avoid "chemical restraints," policies and guidelines have been implemented to curb the use of medications for behavioral and psychological symptoms of dementia (BPSD). Antipsychotics have been particularly targeted because of their rare severe side effects. Consequently, caregiver directed non-pharmacologic therapies have increased while medication use for BPSD has diminished. Despite such initiatives, however, antipsychotics continue to be prescribed "off-label" for roughly 20% of nursing home patients. How caregivers impact management approaches and prescribing decisions for BPSD, including antipsychotic use, is poorly understood. Aim: assesses experiences and perceptions of family and nursing caregivers regarding factors influencing medication decisions for BPSD. Research Design and Methods: Semi-structured interviews, analyzed via template, immersion and crystallization, and thematic development. Thirty-two participants from Northwestern Virginia representing five groups of caregivers for dementia patients were interviewed: families of community-dwelling, assisted living, and nursing home patients, and nurses from the same assisted living/nursing home facilities. Results: Caregivers described three major themes regarding medications: (a) Systemic barriers exist for non-pharmacologic BPSD therapies. (b) Medications have few barriers, and seem generally effective and safe. (c) When non-pharmacologic measures fail, medications, including antipsychotics, may be necessary and appropriate for palliation of patient distress. Discussion and Implications: To further reduce medications for BPSD, obstacles to services and alternative therapies must be mitigated. Caregiver perceptions that medications are generally safe and effective contribute to their continued use. Guidelines and policies for BPSD management should incorporate the caregiver position that medications, including antipsychotics, are sometimes justified and required to alleviate patient suffering.

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia.

BACKGROUND: Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD. METHODS: Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primary-care practice for at least 3 years in Northwestern Virginia. RESULTS: PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management. CONCLUSIONS: PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development.

BMI at birth and overweight at age four.

BACKGROUND: Extensive investigation has established that an elevated weight at birth is associated with subsequent obesity and obesity related negative health outcomes. The significance of overweight at birth, however, remains ill-defined. Historically, it has been difficult to approximate adiposity in infancy in a way that is both simple and meaningful. Body-mass-index (BMI) growth charts for children younger than two years of age only became available in 2006 when published by the WHO. METHODS: This retrospective cohort analysis utilised anthropometric data extracted from the electronic medical record of a large integrated healthcare system in North Carolina. BMI and weight-for-age (WFA) >85% of WHO growth charts measured newborn overweight and macrosomia respectively. Logistic regression models assessed the associations between newborn macrosomia and overweight and overweight at 4 years of age, as well as associations with maternal BMI. Models included demographic data, gestational age, and maternal diabetes status as covariates. RESULTS: Both BMI and WFA >85% at birth were significantly associated with overweight at age 4 years. However, the greater odds of overweight was associated with newborn BMI >85%, with an adjusted odds ratio (AOR) of 2.08 (95% confidence interval [CI]: 1.4-3.08) versus 1.57 (95% CI: 1.08-2.27). Maternal obesity was also more robustly correlated with newborn BMI >85%, AOR of 4.14 (95% CI: 1.6-10.7), than with newborn WFA >85%, AOR of 3.09 (95% CI: 1.41-6.77). CONCLUSIONS: BMI >85% at birth is independently associated with overweight at 4 years. Newborn overweight is perhaps superior to newborn macrosomia in predicting overweight at age 4.

Changes in Asthma Maintenance Therapy Prescribing Patterns Following the 2006 Long-acting ß-Agonist FDA Drug Warning.

PURPOSE: The US Food and Drug Administration issued a boxed warning on all products containing a long-acting ß-agonist (LABA) in March 2006, after the findings from a trial suggested an increased risk for death in patients treated with salmeterol monotherapy. Almost nothing is known about the impact of this warning on LABA prescribing patterns or on clinicians' approaches to asthma maintenance therapy. METHODS: A cohort of asthmatic adults on LABA therapy was retrospectively identified from a Baltimore-area Medicaid data warehouse. Pharmacy claims were used for determining the utilization rates of all asthma maintenance medications. Rates from the 6-month period before the warning (September 1, 2005, to February 28, 2006) were compared with rates from a similar 6-month period 1 year afterward (September 1, 2006, to February 28, 2007). The demographic characteristics of patients who continued LABA use were compared with those of discontinuers. In LABA discontinuers, utilization of alternative maintenance drugs was assessed. FINDINGS: In this cohort of 455 asthmatic patients, LABAs were prescribed only in combination with inhaled corticosteroids. Following the warning, 53% of patients discontinued LABA use, and the mean number of LABA prescription fills per patient decreased from 2.6 to 1.8 (P < 0.0001). Concurrently, the use of inhaled corticosteroids increased from 0.3 to 0.8 fills per patient (P < 0.0001). LABA continuers were younger (P = 0.0005), more likely to be black (P = 0.0079), and more consistent with LABA fills prewarning (P < 0.0001). Of the 243 LABA discontinuers, 155 were placed on no alternative maintenance therapy. IMPLICATIONS: The management of asthma changed significantly after the LABA warning. The use of LABAs combined with inhaled corticosteroids plummeted, while the use of inhaled corticosteroid monotherapy increased. More than half of patients who discontinued LABAs were not placed on alternative maintenance therapy.