Neuroprognostication for Patients with Amyotrophic Lateral Sclerosis: An Updated, Evidence-Based Review.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that presents and progresses in various ways, making prognostication difficult. Several paradigms exist for providers to elucidate prognosis in a way that addresses not only the amount of time a patient has to live, but also a patient's quality of their life moving forward. Prognostication, with regard to both survivability and quality of life, is impacted by several features that include, but are not limited to, patient demographics, clinical features on presentation, and over time, access to therapy, and access to multidisciplinary clinics. An understanding of the impact that these features have on the life of a patient with ALS can help providers to develop a better and more personalized approach for patients related to their clinical prognosis after a diagnosis is made. The ultimate goal of prognostication is to empower patients with ALS to take control and make decisions with their care teams to ensure that their goals are addressed and met.

Development and Dissemination of a Neurology Palliative Care Curriculum: Education in Palliative and End-of-Life Care Neurology.

Despite increasing awareness of the importance of a palliative care approach to meet the needs of persons living with neurologic illness, residency and fellowship programs report meeting this educational need due to a limited pool of neuropalliative care educators and a lack of adequate educational resources. To meet this need, a group of experts in neuropalliative care and palliative medicine leveraged resources from the Education in Palliative and End-of-life Care (EPEC) program and the National Institutes of Nursing Research to create a library of modules addressing topics relevant for neurology trainees, palliative medicine fellows, and clinicians in practice. In this article, we describe the development and dissemination plan of the EPEC Neurology program, initial evidence of efficacy, and opportunities for neurology educators and health services researchers to use these resources.

The Role of Specialty Palliative Care for Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive and incurable neurodegenerative disease resulting in the loss of motor neurons, eventually leading to death. ALS results in complex physical, emotional, and spiritual care needs. Specialty Palliative Care (SPC) is a medical specialty for patients with serious illness that provides an extra layer of support through complicated symptom management, goals of care conversations, and support to patients and families during hard times. Using MEDLINE, APA Psychinfo, and Dynamed databases, we reviewed the literature of SPC in ALS to inform and support an expert opinion perspective on this topic. This manuscript focuses on several key areas of SPC for ALS including insurance and care models, advance care planning, symptom management, quality of life, caregiver support, and end-of-life care. Recommendations to improve specialty palliative care for patients with ALS are reviewed in the discussion section.

Compassionate Removal of Heated High-Flow Nasal Cannula for End of Life: Case Series and Protocol Development.

Patients often receive burdensome care at the end of life in the form of interventions that may need to be removed. Heated high-flow oxygen delivered through a nasal cannula (HHFNC) is one such intervention that can be delivered in the hospital yet is rarely available outside of this setting. During the COVID-19 (coronavirus disease 2019) pandemic, health care systems continue to face the possibility of rationing critical life-sustaining equipment that may include HHFNC. We present a clinical protocol designed for weaning HHFNC to allow a natural death and ensuring adequate symptom management throughout the process. This was a retrospective chart review of 8 patients seen by an inpatient palliative care service of an academic tertiary referral hospital who underwent terminal weaning of HHFNC using a structured protocol to manage dyspnea. Eight patients with diverse medical diagnoses, including COVID-19 pneumonia, underwent terminal weaning of HHFNC according to the clinical protocol with 4 down-titrations of approximately 25% for both fraction of inspired oxygen and liter flow with preemptive boluses of opioid and benzodiazepine. Clinical documentation supported good symptom control throughout the weaning process. This case series provides preliminary evidence that the clinical protocol proposed has the ability to ensure comfort through terminal weaning of HHFNC.

Models of outpatient neuropalliative care for patients with amyotrophic lateral sclerosis.

OBJECTIVE: To describe some current models of outpatient neuropalliative care (NPC) available to patients with amyotrophic lateral sclerosis at different institutions within the United States. METHODS: Six NPC physicians were asked to contribute written descriptions about the PC available in their ALS clinics. Descriptions were then compiled and assessed for similarities and differences. RESULTS: All clinics are multidisciplinary, with regular appointments every 3 months and similar appointment times for new visits (60-120 minutes) and follow-up visits (20-45 minutes). Four clinics have an NPC specialist embedded within the ALS clinic, 1 institution has a separate clinic for NPC, and 1 institution has both. The NPC physician at 5 institutions is a neurologist with formal palliative care training and at 1 institution is an internist with formal palliative care training. NPC is part of routine care for all patients at 2 institutions, and the primary reasons for consultation are goals of care (GOC) and severe symptom management. CONCLUSION: NPC is provided to patients with ALS heterogeneously throughout the United States with some variation in services and delivery, but all clinics are addressing similar core needs. Given the poor prognosis and high PC needs, those with ALS are the ideal patients to receive NPC. Future studies are necessary given the paucity of data available to determine best practices and to better define meaningful outcomes.

Motor Neuron Disease: Pathophysiology, Diagnosis, and Management.

Patients with motor neuron diseases may present to primary care clinic or may be initially encountered in the inpatient setting. Timely diagnosis of these conditions is a key factor in early intervention and therapy, and accuracy of diagnosis is of extreme importance, in particular for amyotrophic lateral sclerosis with its poor prognosis. The aim of this review article is to provide a clinical and diagnostic framework for the diagnosis and evaluation of motor neuron disease for primary care physicians.

Hazardous drinking and its correlates among university students in barbados / Bebidas perigosas e seus correlatos entre universitários de barbados / Bebidas peligrosas y sus correlatos entre universitarios de barbados

ABSTRACT Objective: this study investigates the relationship between problematic drinking, gender, age, marijuana consumption, driving under the influence of alcohol and riding with an alcohol intoxicated driver among university students in Barbados. Method: a cross-sectional survey was used to collect data from 371 students, the majority of whom were female (73.6%) and between the ages of 18 and 21 (60.6%). Results: the majority of participants (81.1%) consumed alcohol in the preceding 12 months and 17.2% met the criteria for problematic drinking based on their Alcohol Use Disorders Identification Test score. A significant relationship was uncovered between problematic drinking and student gender, driving under the influence alcohol, riding with an alcohol intoxicated driver and marijuana consumption. Conclusion: further research using a representative sample should be conducted to determine if the findings hold true for the wider student population. Nevertheless, the study highlights the presence of problematic drinking among the students and therefore initiatives should be implemented to reduce and eliminate its occurrence.

RESUMO Objetivo: este estudo investiga a relação entre o uso problemático de bebidas, sexo, idade, consumo de maconha, dirigir sob a influência de álcool e andar com motorista alcoolizado entre estudantes universitários em Barbados. Método: utilizou-se um levantamento transversal para coleta de dados de 371 estudantes, sendo a maioria do sexo feminino (73,6%) e com idade entre 18 e 21 anos (60,6%). Resultados: a maioria dos participantes (81,1%) consumiu álcool nos últimos 12 meses e 17,2% preencheram os critérios para uso problemático de bebidas com base na pontuação do Teste de Identificação dos Distúrbios do Uso de Álcool. Uma relação significativa foi descoberta entre o uso problemático bebidas e o gênero dos estudantes, dirigir sob a influência do álcool, andar com um motorista alcoolizado e consumir maconha. Conclusão: mais pesquisas usando uma amostra representativa devem ser conduzidas para determinar se as descobertas são verdadeiras para a população estudantil mais abrangente. No entanto, o estudo destaca a presença de consumo de bebidas problemático entre os alunos e, portanto, iniciativas devem ser implementadas para reduzir e eliminar sua ocorrência.

RESUMEN Objetivo: este estudio investiga la relación entre el uso problemático de bebidas, sexo, edad, consumo de marihuana, conducir bajo los efectos del alcohol y conducir con un conductor ebrio entre estudiantes universitarios en Barbados. Método: se utilizó una encuesta transversal para recopilar los datos de 371 estudiantes, la mayoría de ellos mujeres (73,6%) y edades entre 18 y 21 años (60,6%). Resultados: la mayoría de los participantes (81.1%) consumió alcohol en los últimos 12 meses y 17,2% cumplió con los criterios para el uso problemático de bebidas, según el puntaje del Test de Identificación de Trastornos por Consumo de Alcohol. Se descubrió una relación significativa entre el consumo problemático de bebidas y el género de los estudiantes, conducir bajo los efectos del alcohol, conducir con un conductor ebrio y consumir marihuana. Conclusión: se debe realizar una investigación adicional con una muestra representativa para determinar si los hallazgos son ciertos para la población estudiantil en general. Sin embargo, el estudio destaca la presencia del consumo problemático de bebidas entre estudiantes y, por lo tanto, se deben implementar iniciativas para reducir y eliminar su ocurrencia.

Burnout, career satisfaction, and well-being among US neurology residents and fellows in 2016.

OBJECTIVE: To study prevalence of and factors contributing to burnout, career satisfaction, and well-being in US neurology residents and fellows. METHODS: A total of 938 US American Academy of Neurology member neurology residents and fellows were surveyed using standardized measures of burnout, career satisfaction, and well-being from January 19 to March 21, 2016. RESULTS: Response rate was 37.7% (354/938); about 2/3 of responders were residents and 1/3 were fellows. Median age of participants was 32 years and 51.1% were female. Seventy-three percent of residents and 55% of fellows had at least one symptom of burnout, the difference largely related to higher scores for depersonalization among residents. For residents, greater satisfaction with work-life balance, meaning in work, and older age were associated with lower risk of burnout; for fellows, greater satisfaction with work-life balance and effective support staff were associated with lower risk of burnout. Trainees experiencing burnout were less likely to report career satisfaction. Career satisfaction was more likely among those reporting meaning in work and more likely for those working in the Midwest compared with the Northeast region. CONCLUSIONS: Burnout is common in neurology residents and fellows. Lack of work-life balance and lack of meaning in work were associated with reduced career satisfaction and increased risk of burnout. These results should inform approaches to reduce burnout and promote career satisfaction and well-being in US neurology trainees.

Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

BACKGROUND: Genetic alterations are significant causes of epilepsy syndromes; especially early-onset epileptic encephalopathies and voltage-gated sodium channelopathies are among the best described. Mutations in the SCN2A subunit of voltage-gated sodium channels have been associated with benign familial neonatal-infantile seizures, generalized epilepsy febrile seizures plus, and an early-onset infantile epileptic encephalopathy. METHOD: We describe two infants with medically refractory seizures due to a de novo SCN2A mutation. RESULTS: The first child responded to intravenous lidocaine with significant reduction in seizure frequency and was successfully transitioned to enteral mexiletine. Mexiletine was subsequently used in a second infant with reduction in seizure frequency. CONCLUSION: Class 1b antiarrhythmic agents, lidocaine and mexiletine, may be useful in infants with medically refractory early infantile epileptic encephalopathy secondary to mutations in SCN2A.

Century-scale trends and seasonality in pH and temperature for shallow zones of the Bering Sea.

No records exist to evaluate long-term pH dynamics in high-latitude oceans, which have the greatest probability of rapid acidification from anthropogenic CO2 emissions. We reconstructed both seasonal variability and anthropogenic change in seawater pH and temperature by using laser ablation high-resolution 2D images of stable boron isotopes (δ(11)B) on a long-lived coralline alga that grew continuously through the 20th century. Analyses focused on four multiannual growth segments. We show a long-term decline of 0.08 ± 0.01 pH units between the end of the 19th and 20th century, which is consistent with atmospheric CO2 records. Additionally, a strong seasonal cycle (∼ 0.22 pH units) is observed and interpreted as episodic annual pH increases caused by the consumption of CO2 during strong algal (kelp) growth in spring and summer. The rate of acidification intensifies from -0.006 ± 0.007 pH units per decade (between 1920s and 1960s) to -0.019 ± 0.009 pH units per decade (between 1960s and 1990s), and the episodic pH increases show a continuous shift to earlier times of the year throughout the centennial record. This is indicative of ecosystem shifts in shallow water algal productivity in this high-latitude habitat resulting from warming and acidification.

Phenotypic plasticity of coralline algae in a High CO2 world.

It is important to understand how marine calcifying organisms may acclimatize to ocean acidification to assess their survival over the coming century. We cultured the cold water coralline algae, Lithothamnion glaciale, under elevated pCO2 (408, 566, 770, and 1024 µatm) for 10 months. The results show that the cell (inter and intra) wall thickness is maintained, but there is a reduction in growth rate (linear extension) at all elevated pCO2. Furthermore a decrease in Mg content at the two highest CO2 treatments was observed. Comparison between our data and that at 3 months from the same long-term experiment shows that the acclimation differs over time since at 3 months, the samples cultured under high pCO2 showed a reduction in the cell (inter and intra) wall thickness but a maintained growth rate. This suggests a reallocation of the energy budget between 3 and 10 months and highlights the high degree plasticity that is present. This might provide a selective advantage in future high CO2 world.

Surviving rapid climate change in the deep sea during the Paleogene hyperthermals.

Predicting the impact of ongoing anthropogenic CO2 emissions on calcifying marine organisms is complex, owing to the synergy between direct changes (acidification) and indirect changes through climate change (e.g., warming, changes in ocean circulation, and deoxygenation). Laboratory experiments, particularly on longer-lived organisms, tend to be too short to reveal the potential of organisms to acclimatize, adapt, or evolve and usually do not incorporate multiple stressors. We studied two examples of rapid carbon release in the geological record, Eocene Thermal Maximum 2 (∼53.2 Ma) and the Paleocene Eocene Thermal Maximum (PETM, ∼55.5 Ma), the best analogs over the last 65 Ma for future ocean acidification related to high atmospheric CO2 levels. We use benthic foraminifers, which suffered severe extinction during the PETM, as a model group. Using synchrotron radiation X-ray tomographic microscopy, we reconstruct the calcification response of survivor species and find, contrary to expectations, that calcification significantly increased during the PETM. In contrast, there was no significant response to the smaller Eocene Thermal Maximum 2, which was associated with a minor change in diversity only. These observations suggest that there is a response threshold for extinction and calcification response, while highlighting the utility of the geological record in helping constrain the sensitivity of biotic response to environmental change.

The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.

This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published.

Ocean acidification weakens the structural integrity of coralline algae.

The uptake of anthropogenic emission of carbon dioxide is resulting in a lowering of the carbonate saturation state and a drop in ocean pH. Understanding how marine calcifying organisms such as coralline algae may acclimatize to ocean acidification is important to understand their survival over the coming century. We present the first long-term perturbation experiment on the cold-water coralline algae, which are important marine calcifiers in the benthic ecosystems particularly at the higher latitudes. Lithothamnion glaciale, after three months incubation, continued to calcify even in undersaturated conditions with a significant trend towards lower growth rates with increasing pCO2 . However, the major changes in the ultra-structure occur by 589 µatm (i.e. in saturated waters). Finite element models of the algae grown at these heightened levels show an increase in the total strain energy of nearly an order of magnitude and an uneven distribution of the stress inside the skeleton when subjected to similar loads as algae grown at ambient levels. This weakening of the structure is likely to reduce the ability of the alga to resist boring by predators and wave energy with severe consequences to the benthic community structure in the immediate future (50 years).

Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure.

Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure.