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Health Findings

Deaths caused by alcohol increasing

Alcohol-related deaths in the U.S. are on the rise, a new study reports.




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Expanding the public health team: a cross-sector workforce

I’ve been talking a lot lately about the importance of working across sectors for public health — of not going it alone to tackle the imposing challenges before us. The ideal public health team is broad and includes not only public health professionals representing the essential services, but also professionals from other disciplines, the general public and students of all stripes.




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COVID-19: APHA serves as trusted voice on outbreak science, funding

Since December, when cases of a then-unknown respiratory disease were first reported in Wuhan, China, APHA has working to share information and ensure that public health has the resources it needs to address COVID-19.




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Federal funding for gun violence prevention research sparks hopes: Priorities, direction being explored

After more than 20 years of minimal funding, the U.S. is opening its purse strings to research on gun violence prevention.




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US public health meets COVID-19 head-on: Pandemic squeezes long-underfunded public health system

Forty miles from the state capital, Jackson County, West Virginia, is home to about 29,000 people and 25 hospital beds. Like much of the state, the rural county is reeling from the opioid epidemic.




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Long-acting, Injectable Buprenorphine: Great Promise, but Significant Barriers to Use

To the Editor—A 30-day injectable form of buprenorphine branded as SublocadeTM (Buprenorphine XR SQ) was approved by the FDA in 2017. This medication is administered by a health care professional subcutaneously in the abdomen to treat opioid use disorder. This long-acting delivery system holds great promise for many patients who have barriers to taking daily transmucosal buprenorphine-containing medications such as those with poor adherence to a daily medication. It is beneficial for those who have difficulty safely storing their medications, including patients who have children in the home, unstable housing, or live with others who have a use disorder. This product is also an option for patients who prefer mono-product buprenorphine. As Buprenorphine XR SQ is administered directly by a health care professional, it does not contain the abuse-deterrent naloxone that some patients feel causes side effects.

There are two ways to acquire Buprenorphine XR SQ: 1) order product from the distributor (buy and bill); or 2) dispensed from a specialty pharmacy for a specific patient (specialty pharmacy) [1]. For the buy and bill option, the health care setting must be certified through the Risk Evaluation and Mitigation Strategy (REMS) program and adhere to dispensing regulations [2]. We found this challenging to implement in the outpatient setting, thus we pursued the specialty pharmacy option. It ultimately took us nearly one year to complete the process.

The following are the barriers we faced with our first attempt. As a controlled substance, the medication must be stored in a refrigerated lockbox. Before...




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A Call to Action for Philanthropy in North Carolina Health Care

The conversation about how we create and maintain health has evolved. We have now clearly expanded our thinking beyond an exclusive focus on traditional medical care, and philanthropy can play an important role




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A Call to Action for North Carolina Legislators on Improving Access to Health

To better the health of all North Carolinians, policymakers must come together to improve access to care, expand broadband, and close the coverage gap.




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It's Time for Private Sector Business to Come to the Health Care Table

With rising costs and below-average outcomes, North Carolina's health care value proposition is upside down. It's time for employers to lead transformative change.




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Historical Geography and Health Equity: An Exploratory View of North Carolina Slavery and Sociohealth Factors

Current health inequities are rooted in more than simple systems failures and inefficiencies. Historical legacy has corrupted health outcomes, and resolution requires both acknowledgment and intention.




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Engaging the Power of Communities for Better Health

Authentically engaging community residents is necessary to impact social drivers of health. Acknowledging the value of residents' lived experiences in the planning, implementation, and financial decisions of community engagement initiatives is key. Sustainability of community engagement initiatives depends on open communication and follow-through on commitments.




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North Carolina's Health Care Transformation to Value: Progress to Date and Further Steps Needed

North Carolina has received national attention for its approach to health care payment and delivery reform. Importantly, payment reform alone is not enough to drive systematic changes in care delivery. We highlight the importance of progress in four complementary areas to achieve system-wide payment and care reform.




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Moving Upstream to Impact Health: Building a Physician Workforce that Understands Social Determinants

Decades of rallying cries from professional societies, medical education and training programs, and government stakeholders have distilled the conversation of social determinants of health (SDOH) from theoretical proposals into practical solutions [1-3]. No longer standing on the precipice of change, we are now in the trenches. The nation's health care system recognizes SDOH as important drivers of health and is taking steps to address them in the practice environment.

More widespread action and attention by the health care system drives the need to train the next generation of physicians in the concepts and actions related to SDOH. This includes SDOH as a core part of the medical curriculum, offering clinical and research experiences and service in the community [4-5]. Unfortunately, to date only a handful of programs have brought this vision to fruition. Across the country, most programs offer educational content that is largely didactic and provided in short or one-time sessions [6]. Though a start, such approaches are insufficient to prepare the next generation of physicians for their important work ahead.

In New Orleans, the NOLA Hotspotters are an interdisciplinary group of medical, public health, nursing, and pharmacy students inspired by the work out of Camden, New Jersey, to "hot spot" patients with high utilization, which is often related to social needs [7]. While the results of the Camden program have been widely discussed following publication of their work, we argue the benefit of such a program exists beyond reduced emergency department visits or health care spending [8]. The...




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Developing a Workforce for Health in North Carolina: Planning for the Future

Among the many trends influencing health and health care delivery over the next decade, three are particularly important: the transition to value-based care and increased focus on population health; the shift of care from acute to community-based settings; and addressing the vulnerability of rural health care systems in North Carolina.




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Toward a Health Data Strategy for North Carolina

In recent years, North Carolina has attracted significant national attention due to numerous health care reforms underway across government and the private sector. These reforms encompass new incentives, new partnerships, and new models of delivering care, and collectively, they have important implications for health care data.




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Investing in Whole Person Health: Working Toward an Integration of Physical, Behavioral, and Social Health

North Carolina is developing a unique and innovative infrastructure to support integrated physical, behavioral, and social health care. Efforts by the North Carolina Department of Health and Human Services, the Foundation for Health Leadership & Innovation, Cone Health, Atrium Health, and the One Charlotte Health Alliance advance our understanding of how to best operationalize the design and payment of integrated services. Best practices such as the collaborative care and primary care behavioral health models reduce inefficiencies and disparities by bringing together teams of primary care and behavioral health care providers.




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Place Matters: From Health and Health Care Disparities to Equity and Liberation

Place—a confluence of the social, economic, political, physical, and built environments—is fundamental to our understanding of health and health inequities among marginalized racial groups in the United States. Moreover, racism, defined as a system of structuring opportunity and assigning value based on the social interpretation of how one looks (i.e., race), has shaped the places people live in North Carolina. This problem is deeply imbedded in all of our systems, from housing to health care, affecting the ability of every resident of the state to flourish and thrive.




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Vital Directions for Health & Health Care: The North Carolina Experience

In 2019, the National Academy of Medicine (NAM) turned to the all-important state level to draw insights on the status of health and health care within the context of the NAM Vital Directions for Health and Health Care initiative. The NAM held a two-day symposium in the Research Triangle to bring together various stakeholders to better understand actions that states and localities are taking to achieve—and the barriers they face in pursuing—more affordable, value-driven quality care and health outcomes. The NAM purposefully chose to pivot to the state level with North Carolina given that it has been at the forefront of health care transformation and illustrates the promise but also the challenges facing US health and health care nationally. A 19-member planning committee, cochaired by NAM President Victor Dzau and Secretary Mandy Cohen of the North Carolina Department of Health and Human Services, selected topics that resonate with the state's activities within the context of the Vital Directions framework, ranging from empowering people and connecting care through the integration of social, physical, and behavioral health to payer alignment though the advancement of new payment models (Figure 1). The priorities discussed during the symposium continue to be central to health reform in North Carolina and are further explored in the commentaries in this issue.




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Acute encephalopathy after head trauma in a patient with a RHOBTB2 mutation

Objective

De novo missense mutations in the RHOBTB2 gene have been described as causative for developmental and epileptic encephalopathy.

Methods

The clinical phenotype of this disorder includes early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorder. Three RHOBTB2 patients have been described with acute encephalopathy and febrile epileptic status. All showed severe EEG abnormalities during this episode and abnormal MRI with hemisphere swelling or reduced diffusion in various brain regions.

Results

We describe the episode of acute encephalopathy after head trauma in a 5-year-old RHOBTB2 patient. At admission, Glasgow coma scale score was E4M4V1. EEG was severely abnormal showing a noncontinuous pattern with slow activity without epileptic activity indicating severe encephalopathy. A second EEG on day 8 was still severely slowed and showed focal delta activity frontotemporal in both hemispheres. Gradually, he recovered, and on day 11, he had regained his normal reactivity, behavior, and mood. Two months after discharge, EEG showed further decrease in slow activity and increase in normal electroencephalographic activity. After discharge, parents noted that he showed more hyperkinetic movements compared to before this period of encephalopathy. Follow-up MRI showed an increment of hippocampal atrophy. In addition, we summarize the clinical characteristics of a second RHOBTB2 patient with increase of focal periventricular atrophy and development of hemiparesis after epileptic status.

Conclusions

Acute encephalopathy in RHOBTB2 patients can also be triggered by head trauma.




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Cerebellar ataxia, neuropathy, hearing loss, and intellectual disability due to AIFM1 mutation

Objective

To describe the clinical and molecular genetic findings in a family segregating a novel mutation in the AIFM1 gene on the X chromosome.

Methods

We studied the clinical features and performed brain MRI scans, nerve conduction studies, audiometry, cognitive testing, and clinical exome sequencing (CES) in the proband, his mother, and maternal uncle. We used in silico tools, X chromosome inactivation assessment, and Western blot analysis to predict the consequences of an AIFM1 variant identified by CES and demonstrate its pathogenicity.

Results

The proband and his maternal uncle presented with childhood-onset nonprogressive cerebellar ataxia, hearing loss, intellectual disability (ID), peripheral neuropathy, and mood and behavioral disorder. The proband's mother had mild cerebellar ataxia, ID, and mood and behavior disorder, but no neuropathy or hearing loss. The 3 subjects shared a variant (c.1195G>A; p.Gly399Ser) in exon 12 of the AIFM1 gene, which is not reported in the exome/genome sequence databases, affecting a critical amino acid for protein function involved in NAD(H) binding and predicted to be pathogenic with very high probability by variant analysis programs. X chromosome inactivation was highly skewed in the proband's mother. The mutation did not cause quantitative changes in protein abundance.

Conclusions

Our report extends the molecular and phenotypic spectrum of AIFM1 mutations. Specific findings include limited progression of neurologic abnormalities after the first decade and the coexistence of mood and behavior disorder. This family also shows the confounding effect on the phenotype of nongenetic factors, such as alcohol and drug use and side effects of medication.




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Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations

Objective

To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden.

Methods

Clinical assessments, targeted genetic studies, neuroimaging with MRI, [18F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with 123I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS).

Results

Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea.

Conclusions

Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.




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Coupled hydraulic and mechanical model of surface uplift due to mine water rebound: implications for mine water heating and cooling schemes

In order to establish sustainable heat loading (heat removal and storage) in abandoned flooded mine workings it is important to understand the geomechanical impact of the cyclical heat loading caused by fluid injection and extraction. This is particularly important where significantly more thermal loading is planned than naturally occurs. A simple calculation shows that the sustainable geothermal heat flux from abandoned coal mines can provide less than a tenth of Scotland's annual domestic heating demand. Any heat removal greater than the natural heat flux will lead to heat mining unless heat storage options are also considered.

As a first step, a steady-state, fully saturated, 2D coupled hydromechanical model of a generalized section of pillar-and-stall workings has been created. Mine water rebound was modelled by increasing the hydrostatic pressure sequentially, in line with monitored mine water-level data from Midlothian, Scotland. The modelled uplift to water-level rise ratio of 1.4 mm m–1 is of the same order of magnitude (1 mm m–1) as that observed through interferometric synthetic aperture radar (InSAR) data in the coalfield due to mine water rebound. The modelled magnitude of shear stress at the pillar corners, as a result of horizontal and vertical displacement, is shown to increase linearly with water level. Mine heat systems are expected to cause smaller changes in pressure than those modelled but the results provide initial implications on the potential geomechanical impacts of mine water heat schemes which abstract or inject water and heat into pillar-and-stall coal mine workings.

Thematic collection: This article is part of the SJG Collection on Early-Career Research available at: https://www.lyellcollection.org/cc/SJG-early-career-research




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Digging deeper: The influence of historical mining on Glasgow's subsurface thermal state to inform geothermal research

Studies of the former NE England coalfield in Tyneside demonstrated that heat flow perturbations in boreholes were due to the entrainment and lateral dispersion of heat from deeper in the subsurface through flooded mine workings. This work assesses the influence of historical mining on geothermal observations across Greater Glasgow. The regional heat flow for Glasgow is 60 mW m–2 and, after correction for palaeoclimate, is estimated as c. 80 mW m–2. An example of reduced heat flow above mine workings is observed at Hallside (c. 10 km SE of Glasgow), where the heat flow through a 352 m deep borehole is c. 14 mW m–2. Similarly, the heat flow across the 199 m deep GGC01 borehole in the Glasgow Geothermal Energy Research Field Site is c. 44 mW m–2. The differences between these values and the expected regional heat flow suggest a significant component of horizontal heat flow into surrounding flooded mine workings. This deduction also influences the quantification of deeper geothermal resources, as extrapolation of the temperature gradient above mine workings would underestimate the temperature at depth. Future projects should consider the influence of historical mining on heat flow when temperature datasets such as these are used in the design of geothermal developments.

Supplementary material: Background information on the chronology of historical mining at each borehole location and a summary of groundwater flow in mine workings beneath Glasgow are available at https://doi.org/10.6084/m9.figshare.c.4681100

Thematic collection: This article is part of the ‘Early Career Research’ available at: https://www.lyellcollection.org/cc/SJG-early-career-research




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Rupture geometries in anisotropic amphibolite recorded by pseudotachylytes in the Gairloch Shear Zone, NW Scotland

Recent earthquakes involving complex multi-fault rupture have increased our appreciation of the variety of rupture geometries and fault interactions that occur within the short duration of coseismic slip. Geometrical complexities are intrinsically linked with spatially heterogeneous slip and stress drop distributions, and hence need incorporating into seismic hazard analysis. Studies of exhumed ancient fault zones facilitate investigation of rupture processes in the context of lithology and structure at seismogenic depths. In the Gairloch Shear Zone, NW Scotland, foliated amphibolites host pseudotachylytes that record rupture geometries of ancient low-magnitude (≤MW 3) seismicity. Pseudotachylyte faults are commonly foliation parallel, indicating exploitation of foliation planes as weak interfaces for seismic rupture. Discordance and complexity are introduced by fault segmentation, stepovers, branching and brecciated dilational volumes. Pseudotachylyte geometries indicate that slip nucleation initiated simultaneously across several parallel foliation planes with millimetre and centimetre separations, leading to progressive interaction and ultimately linkage of adjacent segments and branches within a single earthquake. Interacting with this structural control, a lithological influence of abundant low disequilibrium melting-point amphibole facilitated coseismic melting, with relatively high coseismic melt pressure encouraging transient dilational sites. These faults elucidate controls and processes that may upscale to large active fault zones hosting major earthquake activity.

Supplementary material: Supplementary Figures 1 and 2, unannotated versions of field photographs displayed in Figures 4a and 5 respectively, are available at https://doi.org/10.6084/m9.figshare.c.4573256

Thematic collection: This article is part of the SJG Collection on Early-Career Research available at: https://www.lyellcollection.org/cc/SJG-early-career-research





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N-Terminal Acetylation Stabilizes SIGMA FACTOR BINDING PROTEIN1 Involved in Salicylic Acid-Primed Cell Death

N-terminal (Nt) acetylation (NTA) is an ample and irreversible cotranslational protein modification catalyzed by ribosome-associated Nt-acetyltransferases. NTA on specific proteins can act as a degradation signal (called an Ac/N-degron) for proteolysis in yeast and mammals. However, in plants, the biological relevance of NTA remains largely unexplored. In this study, we reveal that Arabidopsis (Arabidopsis thaliana) SIGMA FACTOR-BINDING PROTEIN1 (SIB1), a transcription coregulator and a positive regulator of salicylic acid-primed cell death, undergoes an absolute NTA on the initiator Met; Nt-acetyltransferase B (NatB) partly contributes to this modification. While NTA results in destabilization of certain target proteins, our genetic and biochemical analyses revealed that plant NatB-involved NTA instead renders SIB1 more stable. Given that the ubiquitin/proteasome system stimulates SIB1 degradation, it seems that the NTA-conferred stability ensures the timely expression of SIB1-dependent genes, mostly related to immune responses. Taking our findings together, here we report a noncanonical NTA-driven protein stabilization in land plants.




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RNA Interference-Based Screen Reveals Concerted Functions of MEKK2 and CRCK3 in Plant Cell Death Regulation

A wide variety of intrinsic and extrinsic cues lead to cell death with unclear mechanisms. The infertility of some death mutants often hurdles the classical suppressor screens for death regulators. We have developed a transient RNA interference (RNAi)-based screen using a virus-induced gene silencing approach to understand diverse cell death pathways in Arabidopsis (Arabidopsis thaliana). One death pathway is due to the depletion of a MAP kinase (MAPK) cascade, consisting of MAPK kinase kinase 1 (MEKK1), MKK1/2, and MPK4, which depends on a nucleotide-binding site Leu-rich repeat (NLR) protein SUMM2. Silencing of MEKK1 by virus-induced gene silencing resembles the mekk1 mutant with autoimmunity and defense activation. The RNAi-based screen toward Arabidopsis T-DNA insertion lines identified SUMM2, MEKK2, and Calmodulin-binding receptor-like cytoplasmic kinase 3 (CRCK3) to be vital regulators of RNAi MEKK1-induced cell death, consistent with the reports of their requirement in the mekk1-mkk1/2-mpk4 death pathway. Similar with MEKK2, overexpression of CRCK3 caused dosage- and SUMM2-dependent cell death, and the transcripts of CRCK3 were up-regulated in mekk1, mkk1/2, and mpk4. MEKK2-induced cell death depends on CRCK3. Interestingly, CRCK3-induced cell death also depends on MEKK2, consistent with the biochemical data that MEKK2 complexes with CRCK3. Furthermore, the kinase activity of CRCK3 is essential, whereas the kinase activity of MEKK2 is dispensable, for triggering cell death. Our studies suggest that MEKK2 and CRCK3 exert concerted functions in the control of NLR SUMM2 activation and MEKK2 may play a structural role, rather than function as a kinase, in regulating CRCK3 protein stability.




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MtSSPdb: A New Database for the Small Secreted Peptide Research Community




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Severe Pulmonary Hypertension Management Across Europe (PHAROS): an ERS Clinical Research Collaboration

The past 20 years have seen major advances in the understanding and treatment of pulmonary arterial hypertension (PAH; group 1 of the pulmonary hypertension (PH) clinical classification) [1]. A strong basis of knowledge has been acquired in: 1) large randomised clinical trials for drug development; 2) national registries for epidemiology and outcome; and 3) smaller studies on the pathophysiological mechanisms of the disease. This knowledge has been reviewed at World Symposia on Pulmonary Hypertension (the most recent in 2018 [2]) and summarised in European Respiratory Society (ERS)/European Society of Cardiology (ESC) clinical guidelines (the most recent in 2015 [3, 4]). We are, however, much less knowledgeable on specific aspects such as 1) the implementation of guidelines and access to therapies in different European countries; 2) the management of PH crises and progressive (acute on chronic) heart failure; and 3) other groups of PH, such as PH due to lung diseases. Therapeutic strategies also need to be optimised, in particular regarding the combination of drugs, the use of anticoagulants, the place for new medications targeting different pathophysiological pathways, etc.




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A clinically significant bronchodilator response in children: how should it be measured?

We thank F. Guezguez and H. Ben Saad for raising important questions on recommendations for assessing a bronchodilator response (BDR) in children. The authors summarise how recommended outcome measures and cut-offs for BDR in children vary between guidelines, and raise questions about our study [1].




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Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.

The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of –2.09 (95% CI –2.78– –1.40) mmHg for systolic BP and –1.92 (95% CI –2.40– –1.43) mmHg for diastolic BP and –1.27 (95% CI –2.34– –0.20) mmHg for systolic BP and –1.11 (95% CI –1.82– –0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP –2.93 mmHg), with uncontrolled BP at baseline (systolic BP –4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP –7.57 mmHg).

Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.




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European Respiratory Journal




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Team conflict and the neurologist

Collaboration within a complicated organization is inherently challenging and can be fraught with discord. Recent emphasis on interdisciplinary and collaborative teamwork in neurology has brought this issue to the forefront of daily practice. The health care system can be complex and opaque, and the stakes—human life—are high. Medical team conflict has been associated with decreased subjective effectiveness, less job satisfaction, and increase in errors. As specialists, neurologists are necessarily embedded within a network of providers and must be adept in the understanding and management of conflictual situations. For the practicing neurologist, it is important to understand team conflict dynamics. Here, management strategies are provided that illustrate how individual neurologists can serve as effective leaders who mitigate harmful effects and capitalize on benefits of team conflict on performance.




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Immediate reactions with glatiramer acetate: Diagnosis of allergy and desensitization protocols

Purpose of review

Diverse adverse events have been associated with administration of glatiramer acetate (GA), mainly local reactions at the injection site. Other, less frequent generalized reactions include isolated postinjection reactions and anaphylaxis, which may lead to discontinuation of GA.

Recent findings

Close collaboration between the allergy and neurology departments is needed to study adverse reactions to GA. The allergy study should include a detailed history and skin prick and intradermal tests with GA and, if possible, determination of specific IgE levels. Furthermore, the implication of other drugs should be ruled out.

Summary

An accurate diagnosis of reactions to GA is essential if we are to confirm or rule out allergy to GA. When an allergy diagnosis is confirmed or firmly suspected based on clinical evidence, desensitization protocols are increasingly seen as safe methods for reintroduction of GA.




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Levodopa-induced dyskinesia in dementia with Lewy bodies and Parkinson disease with dementia

Objective

To investigate the frequency of levodopa-induced dyskinesia in dementia with Lewy bodies (DLBs) and Parkinson disease with dementia (PDD) and compare these frequencies with patients with incident Parkinson disease (PD) through a population-based cohort study.

Methods

We identified all patients with DLB, PDD, and PD without dementia in a 1991–2010 population-based parkinsonism-incident cohort, in Olmsted County, Minnesota. We abstracted information about levodopa-induced dyskinesia. We compared patients with DLB and PDD with dyskinesia with patients with PD from the same cohort.

Results

Levodopa use and dyskinesia data were available for 141/143 (98.6%) patients with a diagnosis of either DLB or PDD; 87 (61.7%), treated with levodopa. Dyskinesia was documented in 12.6% (8 DLB and 3 PDD) of levodopa-treated patients. Among these patients, median parkinsonism diagnosis age was 74 years (range: 64–80 years); 63.6%, male. The median interval from levodopa initiation to dyskinesia onset was 2 years (range: 3 months–4 years); the median daily levodopa dosage was 600 mg (range: 50–1,600 mg). Dyskinesia severity led to levodopa adjustments in 5 patients, and all improved. Patients with dyskinesia were diagnosed with parkinsonism at a significantly younger age compared with patients without dyskinesia (p < 0.001). Levodopa dosage was unrelated to increased risk of dyskinesias among DLB and PDD. In contrast, 30.1% of levodopa-treated patients with PD developed dyskinesia. In age-, sex-, and levodopa dosage–adjusted models, Patients with DLB and PDD each had lower odds of developing dyskinesia than patients with PD (odds ratio = 0.42, 95% CI 0.21–0.88; p = 0.02).

Conclusions

The dyskinesia risk for levodopa-treated patients with DLB or PDD was substantially less than for levodopa-treated patients with PD.




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Neurology consults in emergency departments: Opportunities to streamline care

Objective

To use the variations in neurology consultations requested by emergency department (ED) physicians to identify opportunities to implement multidisciplinary interventions in an effort to reduce ED overcrowding.

Methods

We retrospectively analyzed ED visits across 3 urban hospitals to determine the top 10 most common chief complaints leading to neurology consultation. For each complaint, we evaluated the likelihood of consultation, admission rate, admitting services, and provider-to-provider variability of consultation.

Results

Of 145,331 ED encounters analyzed, 3,087 (2.2%) involved a neurology consult, most commonly with chief complaints of acute-onset neurologic deficit, subacute neurologic deficit, or altered mental status. ED providers varied most in their consultation for acute-onset neurologic deficit, dizziness, and headache. Neurology consultation was associated with a 2.3-hour-longer length of stay (LOS) (95% CI: 1.6–3.1). Headache in particular has an average of 6.7-hour-longer ED LOS associated with consultation, followed by weakness or extremity weakness (4.4 hours) and numbness (4.1 hours). The largest estimated cumulative difference (number of patients with the specific consultation multiplied by estimated difference in LOS) belongs to headache, altered mental status, and seizures.

Conclusion

A systematic approach to identify variability in neurology consultation utilization and its effect on ED LOS helps pinpoint the conditions most likely to benefit from protocolized pathways.




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Factors associated with 30-day readmission for patients hospitalized for seizures

Background

We sought to determine the cumulative incidence of readmissions after a seizure-related hospitalization and identify risk factors and readmission diagnoses.

Methods

We performed a retrospective cohort study of adult patients hospitalized with a primary discharge diagnosis of seizure (International Classification of Diseases, Ninth Edition, Clinical Modification codes 345.xx and 780.3x) using the State Inpatient Databases across 11 states from 2009 to 2012. Hospital and community characteristics were obtained from the American Hospital Association and Robert Wood Johnson Foundation. We performed logistic regressions to explore effects of patient, hospital, and community factors on readmissions within 30 days of discharge.

Results

Of 98,712 patients, 13,929 (14%) were readmitted within 30 days. Reasons for readmission included epilepsy/convulsions (30% of readmitted patients), mood disorders (5%), schizophrenia (4%), and septicemia (4%). The strongest predictors of readmission were diagnoses of CNS tumor (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9–2.4) or psychosis (OR 1.8, 95% CI 1.7–1.8), urgent index admission (OR 2.0, 95% CI 1.8–2.2), transfer to nonacute facilities (OR 1.7, 95% CI 1.6–1.8), long length of stay (OR 1.7, 95% CI 1.6–1.8), and for-profit hospitals (OR 1.7, 95% CI 1.6–1.8). Our main model's c-statistic was 0.66. Predictors of readmission for status epilepticus included index admission for status epilepticus (OR 3.5, 95% CI 2.6–4.7), low hospital epilepsy volume (OR 0.4, 95% CI 0.3–0.7), and rural hospitals (OR 4.8, 95% CI 2.1–10.9).

Conclusion

Readmission is common after hospitalization for seizures. Prevention strategies should focus on recurrent seizures, the most common readmission diagnosis. Many factors were associated with readmission, although readmissions remain challenging to predict.




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Cerebral venous thrombosis: Associations between disease severity and cardiac markers

Background

Plasma cardiac troponin (cTn) elevation occurs in acute ischemic stroke and intracranial hemorrhage and can suggest a poor prognosis. Because acute cerebral venous thrombosis (CVT) might lead to venous stasis, which could result in cardiac stress, it is important to evaluate whether cTn elevation occurs in patients with CVT.

Methods

Inpatients at Johns Hopkins Hospital from 2005 to 2015 meeting the following criteria were included: CVT (ICD-9 codes with radiologic confirmation) and available admission electrocardiogram (ECG) and cTn level. In regression models, presence of ECG abnormalities and cTn elevation (>0.06 ng/mL) were evaluated as dependent variables in separate models, with location and severity of CVT involvement as independent variables, adjusted for age, sex, and hypertension.

Results

Of 81 patients with CVST, 53 (66%) met the inclusion criteria. Participants were, on average, aged 42 years, white (71%), and female (66%). The left transverse sinus was most commonly thrombosed (47%), with 66% having >2 veins thrombosed. Twenty-two (41%) had cTn elevation. Odds of cTn elevation increased per each additional vein thrombosed (adjusted OR 2.79, 95% CI [1.08–7.23]). Of those with deep venous involvement, 37.5% had cTn elevation compared with 4.4% without deep clots (p = 0.02). Venous infarction (n = 15) was associated with a higher mean cTn (0.14 vs 0.02 ng/mL, p = 0.009) and was predictive of a higher cTn in adjusted models (β = 0.15, 95% CI [0.06–0.25]).

Conclusions

In this single-center cohort study, markers of CVT severity were associated with increased odds of cTn elevation; further investigation is needed to elucidate causality and significance.




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Machine learning as a diagnostic decision aid for patients with transient loss of consciousness

Background

Transient loss of consciousness (TLOC) is a common reason for presentation to primary/emergency care; over 90% are because of epilepsy, syncope, or psychogenic non-epileptic seizures (PNES). Misdiagnoses are common, and there are currently no validated decision rules to aid diagnosis and management. We seek to explore the utility of machine-learning techniques to develop a short diagnostic instrument by extracting features with optimal discriminatory values from responses to detailed questionnaires about TLOC manifestations and comorbidities (86 questions to patients, 31 to TLOC witnesses).

Methods

Multi-center retrospective self- and witness-report questionnaire study in secondary care settings. Feature selection was performed by an iterative algorithm based on random forest analysis. Data were randomly divided in a 2:1 ratio into training and validation sets (163:86 for all data; 208:92 for analysis excluding witness reports).

Results

Three hundred patients with proven diagnoses (100 each: epilepsy, syncope and PNES) were recruited from epilepsy and syncope services. Two hundred forty-nine completed patient and witness questionnaires: 86 epilepsy (64 female), 84 PNES (61 female), and 79 syncope (59 female). Responses to 36 questions optimally predicted diagnoses. A classifier trained on these features classified 74/86 (86.0% [95% confidence interval 76.9%–92.6%]) of patients correctly in validation (100 [86.7%–100%] syncope, 85.7 [67.3%–96.0%] epilepsy, 75.0 [56.6%–88.5%] PNES). Excluding witness reports, 34 features provided optimal prediction (classifier accuracy of 72/92 [78.3 (68.4%–86.2%)] in validation, 83.8 [68.0%–93.8%] syncope, 81.5 [61.9%–93.7%] epilepsy, 67.9 [47.7%–84.1%] PNES).

Conclusions

A tool based on patient symptoms/comorbidities and witness reports separates well between syncope and other common causes of TLOC. It can help to differentiate epilepsy and PNES. Validated decision rules may improve diagnostic processes and reduce misdiagnosis rates.

Classification of evidence

This study provides Class III evidence that for patients with TLOC, patient and witness questionnaires discriminate between syncope, epilepsy and PNES.




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Reader response: Functional neurologic disorders: Bringing the informal and hidden curriculum to light

I read with interest the editorial by Strom1 about functional neurologic disorders (FNDs). As a treating physician, I have struggled with the multiple diagnostic labels attached to these patients by physicians of different medical specialties during the course of their clinical disease presentation. A neurologist may assign a patient who presents with chronic fatigue the diagnostic labels of narcolepsy, idiopathic hypersomnia, or chronic Lyme disease. A rheumatologist may assign the label of collagen vascular disease, and a psychiatrist may diagnose depression. This diagnostic ambiguity is troublesome for patients and clinicians alike. I contend that even the term FND needs to be revisited. A patient should be broadly labeled as having a functional disorder and only after characterization sublabeled and referred to an appropriate specialty physician.




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Author response: Symptom burden among individuals with Parkinson disease: A national survey

We appreciate the readers' comments on the prevalence and impact of apathy on quality of life among individuals with Parkinson disease. In constructing our survey instrument, we discussed the inclusion of apathy as a symptom. However, we ultimately opted against inclusion because of concerns about the specificity of terminology in our online survey. Patients and care partners may not be familiar with the term "apathy,"and near-synonyms such as "reduced motivation" have substantial overlap with other nonmotor features. Still, as the readers point out, apathy is extremely common and under-recognized. Similar to many of the nonmotor symptoms identified in our study,1 we agree that clinicians should be screening for apathy among those with Parkinson disease.




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Reader response: Symptom burden among individuals with Parkinson disease: A national survey

We read with great interest the study by Tarolli et al.,1 which explored the burden of disease in Parkinson disease (PD) by evaluating the prevalence of nonmotor symptoms and their association with quality of life. The authors selected nonmotor symptoms based on literature review, expert opinions, and patient interviews. We note that apathy, which has major consequences for patients and carers, was not included as a relevant nonmotor symptom in their study. We performed a subcohort analysis of 60 patients from a study of pain in PD in 110 outpatients (PaCoMo-study, registered trial number: NL6311402917 [toetsingonline.nl]). We retrospectively reviewed the medical records to check whether the clinician identified apathy in these patients in the previous year, which was the case in 15% of the patients (n = 9). Blind to those results, patients were examined with the Apathy Scale (AS).2 In total, 63.3% (n = 38) of the patients scored positive on the AS. Only 18.4% of the patients who scored positive on the AS were also classified or mentioned with apathy in the medical records by clinicians.




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Progressive supranuclear palsy and pawpaw

Consider consumption of annonacin-containing plant products, including pawpaw, as a possible environmental risk factor for atypical parkinsonism.




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Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).

To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.

This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high–nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.




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Emerging Issues in Male Adolescent Sexual and Reproductive Health Care

Pediatricians are encouraged to address male adolescent sexual and reproductive health on a regular basis, including taking a sexual history, discussing healthy sexuality, performing an appropriate physical examination, providing patient-centered and age-appropriate anticipatory guidance, and administering appropriate vaccinations. These services can be provided to male adolescent patients in a confidential and culturally appropriate manner, can promote healthy sexual relationships and responsibility, can and involve parents in age-appropriate discussions about sexual health.




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Ames SG, Davis BS, Marin JR, L. Fink EL, Olson LM, Gausche-Hill M, Kahn JM. Emergency Department Pediatric Readiness and Mortality in Critically Ill Children. Pediatrics. 2019;144(3):e20190568




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Implicit Bias in Pediatrics: An Emerging Focus in Health Equity Research




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Early and Often: The Need for Comprehensive Discussion of Treatment-Induced Cancer Late Effects




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Ahmed A, Fend PI, Gaensbauer JT, Reves RR, Khurana R, Salcedo K, Punnoose R, Katz DJ, for the TUBERCULOSIS EPIDEMIOLOGIC STUDIES CONSORTIUM. Interferon-{gamma} Release Assays in Children <15 Years of Age. Pediatrics. 2020:145(1):e20191930




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Family Values Means Covering Families: Parents Need to Focus on Parenting, Not Access to Care