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.

De Novo and Dominantly Inherited SPTAN1 Mutations Cause Spastic Paraplegia and Cerebellar Ataxia.

BACKGROUND: Pathogenic variants in SPTAN1 have been linked to a remarkably broad phenotypical spectrum. Clinical presentations include epileptic syndromes, intellectual disability, and hereditary motor neuropathy. OBJECTIVES: We investigated the role of SPTAN1 variants in rare neurological disorders such as ataxia and spastic paraplegia. METHODS: We screened 10,000 NGS datasets across two international consortia and one local database, indicative of the level of international collaboration currently required to identify genes causative for rare disease. We performed in silico modeling of the identified SPTAN1 variants. RESULTS: We describe 22 patients from 14 families with five novel SPTAN1 variants. Of six patients with cerebellar ataxia, four carry a de novo SPTAN1 variant and two show a sporadic inheritance. In this group, one variant (p.Lys2083del) is recurrent in four patients. Two patients have novel de novo missense mutations (p.Arg1098Cys, p.Arg1624Cys) associated with cerebellar ataxia, in one patient accompanied by intellectual disability and epilepsy. We furthermore report a recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia from seven families with a dominant inheritance pattern in four and a de novo origin in one case. One further patient carrying a de novo missense mutation (p.Gln2205Pro) has a complex spastic ataxic phenotype. Through protein modeling we show that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat. CONCLUSIONS: We show that SPTAN1 is a relevant candidate gene for ataxia and spastic paraplegia. We suggest that for the mutations identified in this study, disruption of the interlinking of spectrin helices could be a key feature of the pathomechanism. © 2022 International Parkinson and Movement Disorder Society.

RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia.

BACKGROUND AND PURPOSE: Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in RFC1 are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to investigate the prevalence of RFC1 repeat expansions in a cohort of HSAN patients. METHODS: After unremarkable whole-exome sequencing (WES) analysis, we performed repeat-primed PCR to detect intronic RFC1 expansions in 12 HSAN families, who all presented with chronic cough. RESULTS: In these patients, 75% carried biallelic expansions of the pathogenic AAGGG motif. Compared with RFC1-/- cases, RFC1+/+ cases presented more consistently with positive sensory and autonomic symptoms. Afferent ataxia was more severe in the RFC1+/+ cohort and cerebellar ataxia was a common feature (21%). CONCLUSIONS: We demonstrate that RFC1 is a frequent cause of (WES-negative) HSAN with chronic cough and ataxia. The diagnostic yield of RFC1 repeat-primed PCR was surprisingly high, given that HSAN is genetically poorly understood. This combination of HSAN, ataxia, and chronic cough symptoms represents a new nosological entity within the neuropathy-ataxia spectrum.

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays.

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.

Autochthonous Cases of Tick-Borne Encephalitis, Belgium, 2020.

We report 3 confirmed autochthonous tick-borne encephalitis cases in Belgium diagnosed during summer 2020. Clinicians should include this viral infection in the differential diagnosis for patients with etiologically unexplained neurologic manifestations, even for persons without recent travel history.

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.

Practice facilitation to promote evidence-based screening and management of unhealthy alcohol use in primary care: a practice-level randomized controlled trial.

BACKGROUND: Unhealthy alcohol use is the third leading cause of preventable death in the United States. Evidence demonstrates that screening for unhealthy alcohol use and providing persons engaged in risky drinking with brief behavioral and counseling interventions improves health outcomes, collectively termed screening and brief interventions. Medication assisted therapy (MAT) is another effective method for treatment of moderate or severe alcohol use disorder. Yet, primary care clinicians are not regularly screening for or treating unhealthy alcohol use. METHODS AND ANALYSIS: We are initiating a clinic-level randomized controlled trial aimed to evaluate how primary care clinicians can impact unhealthy alcohol use through screening, counseling, and MAT. One hundred and 25 primary care practices in the Virginia Ambulatory Care Outcomes Research Network (ACORN) will be engaged; each will receive practice facilitation to promote screening, counseling, and MAT either at the beginning of the trial or at a 6-month control period start date. For each practice, the intervention includes provision of a practice facilitator, learning collaboratives with three practice champions, and clinic-wide information sessions. Clinics will be enrolled for 6-12 months. After completion of the intervention, we will conduct a mixed methods analysis to identify changes in screening rates, increase in provision of brief counseling and interventions as well as MAT, and the reduction of alcohol intake for patients after practices receive practice facilitation. DISCUSSION: This study offers a systematic process for dissemination and implementation of the evidence-based practice of screening, counseling, and treatment for unhealthy alcohol use. Practices will be asked to implement a process for screening, counseling, and treatment based on their practice characteristics, patient population, and workflow. We propose practice facilitation as a robust and feasible intervention to assist in making changes within the practice. We believe that the process can be replicated and used in a broad range of clinical settings; we anticipate this will be supported by our evaluation of this approach. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT04248023, Registered 5 February 2020.

Effect of Rising Temperature on Lyme Disease: Ixodes scapularis Population Dynamics and Borrelia burgdorferi Transmission and Prevalence.

Warmer temperatures are expected to increase the incidence of Lyme disease through enhanced tick maturation rates and a longer season of transmission. In addition, there could be an increased risk of disease export because of infected mobile hosts, usually birds. A temperature-driven seasonal model of Borrelia burgdorferi (Lyme disease) transmission among four host types is constructed as a system of nonlinear ordinary differential equations. The model is developed and parametrized based on a collection of lab and field studies. The model is shown to produce biologically reasonable results for both the tick vector (Ixodes scapularis) and the hosts when compared to a different set of studies. The model is used to predict the response of Lyme disease risk to a mean annual temperature increase, based on current temperature cycles in Hanover, NH. Many of the risk measures suggested by the literature are shown to change with increased mean annual temperature. The most straightforward measure of disease risk is the abundance of infected questing ticks, averaged over a year. Compared to this measure, which is difficult and resource-intensive to track in the field, all other risk measures considered underestimate the rise of risk with rise in mean annual temperature. The measure coming closest was "degree days above zero." Disease prevalence in ticks and hosts showed less increase with rising temperature. Single field measurements at the height of transmission season did not show much change at all with rising temperature.

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.

Overarching pathomechanisms in inherited peripheral neuropathies, spastic paraplegias, and cerebellar ataxias.

International consortia collaborating on the genetics of rare diseases have significantly boosted our understanding of inherited neurological disorders. Historical clinical classification boundaries were drawn between disorders with seemingly different etiologies, such as inherited peripheral neuropathies (IPNs), spastic paraplegias, and cerebellar ataxias. These clinically defined borders are being challenged by the identification of mutations in genes displaying wide phenotypic spectra and by shared pathomechanistic themes, which are valuable indications for therapy development. We highlight common cellular alterations that underlie this genetic landscape, including alteration of cytoskeleton, axonal transport, mitochondrial function, and DNA repair response. Finally, we discuss venues for future research using the long axonopathies of the PNS as a model to explore other neurogenetic disorders.

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.

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.

Distinct features in adult polyglucosan body disease: a case series.

Adult polyglucosan body disease (APBD) is caused by bi-allelic pathogenic variants in GBE1 and typically shows middle age onset urinary symptoms followed by progressive gait disturbances and possibly cognitive decline. Here we present a Belgian cohort of four patients from three families showing both classical and atypical signs of APBD. By clinical phenotyping, detailed neuroimaging of both central nervous system and skeletal muscle, genetic and biochemical testing, we confront our findings with the classical presentation of adult polyglucosan body disease and emphasize the importance of a multidisciplinary approach when diagnosing these patients.

Modeling the sensitivity of cyanobacteria blooms to plausible changes in precipitation and air temperature variability.

Many recent studies have attributed the observed variability of cyanobacteria blooms to meteorological drivers and have projected blooms with worsening societal and ecological impacts under future climate scenarios. Nonetheless, few studies have jointly examined their sensitivity to projected changes in both precipitation and temperature variability. Using an Integrated Assessment Model (IAM) of Lake Champlain's eutrophic Missisquoi Bay, we demonstrate a factorial design approach for evaluating the sensitivity of concentrations of chlorophyll a (chl-a), a cyanobacteria surrogate, to global climate model-informed changes in the central tendency and variability of daily precipitation and air temperature. An Analysis of Variance (ANOVA) and multivariate contour plots highlight synergistic effects of these climatic changes on exceedances of the World Health Organization's moderate 50 µg/L concentration threshold for recreational contact. Although increased precipitation produces greater riverine total phosphorus loads, warmer and drier scenarios produce the most severe blooms due to the greater mobilization and cyanobacteria uptake of legacy phosphorus under these conditions. Increases in daily precipitation variability aggravate blooms most under warmer and wetter scenarios. Greater temperature variability raises exceedances under current air temperatures but reduces them under more severe warming when water temperatures exceed optimal values for cyanobacteria growth more often. Our experiments, controlled for wind-induced changes to lake water quality, signal the importance of larger summer runoff events for curtailing bloom growth through reductions of water temperature, sunlight penetration and stratification. Finally, the importance of sequences of wet and dry periods in generating cyanobacteria blooms motivates future research on bloom responses to changes in interannual climate persistence.

Dilution and amplification effects in Lyme disease: Modeling the effects of reservoir-incompetent hosts on Borrelia burgdorferi sensu stricto transmission.

The literature on Lyme disease includes a lively debate about the paradoxical role of changing deer populations. A decrease in the number of deer will both (1) reduce the incidence of Lyme disease by decreasing the host populations for ticks and therefore tick populations, and (2) enhance the incidence of Lyme disease by offering fewer reservoir-incompetent hosts for ticks, forcing the vector to choose reservoir-competent, and therefore possibly diseased, hosts to feed on. A review of field studies exploring the net impact of changing deer populations shows mixed results. In this manuscript, we investigate the hypothesis that the balance of these two responses to changing deer populations depends on the relative population sizes of reservoir-competent vs. reservoir-incompetent hosts and the presence of host preference in larval and adult stages. A temperature driven seasonal model of Borrelia burgdorferi sensu stricto (cause of Lyme disease) transmission among three host types (reservoir-competent infected and uninfected hosts, and reservoir-incompetent hosts) is constructed as a system of nonlinear ordinary differential equations. The model, which produces biologically reasonable results for both the tick vector Ixodes scapularis Say 1921 and the hosts, is used to investigate the effects of reservoir-incompetent host removal on both tick populations and disease prevalence for various relative population sizes of reservoir-competent hosts vs. reservoir-incompetent hosts. In summary, the simulation results show that the model with host preference appears to be more accurate than the one with no host preference. Given these results, we found that removal of adult I. scapularis(Say) hosts is likely to reduce questing nymph populations. At very low levels questing adult abundance may rise with lack of adult hosts. There is a dilution effect at low reservoir-competent host populations and there is an amplification effect at high reservoir-competent host populations.