Enhancing Nutrition Support for Esophageal Cancer Patients: Understanding Factors Influencing Feeding Tube Utilization.

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.

A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Not a benign motor neuron disease: longitudinal imaging captures relentless motor connectome disintegration in primary lateral sclerosis.

BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre-motor, supplementary motor, cortico-medullary and inter-hemispheric connectivity alterations are less well characterized. METHODS: In a single-centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1-weighted structural, diffusion tensor imaging and resting-state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico-medullary and inter-hemispheric connectivity alterations both cross-sectionally and longitudinally. RESULTS: Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre-motor area involvement, progressive brainstem atrophy, cortico-medullary and inter-hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS. DISCUSSION: Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra- and inter-hemispheric connectivity decline and primary, pre- and supplementary motor cortex degeneration. Simple 'bedside' clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.

Carbon Dioxide Capture Chemistry of Amino Acid Functionalized Metal-Organic Frameworks in Humid Flue Gas.

Metal-organic framework-808 has been functionalized with 11 amino acids (AA) to produce a series of MOF-808-AA structures. The adsorption of CO2 under flue gas conditions revealed that glycine- and dl-lysine-functionalized MOF-808 (MOF-808-Gly and -dl-Lys) have the highest uptake capacities. Enhanced CO2 capture performance in the presence of water was observed and studied by using single-component sorption isotherms, CO2/H2O binary isotherm, and dynamic breakthrough measurements. The key to the favorable performance was uncovered by deciphering the mechanism of CO2 capture in the pores and attributed to the formation of bicarbonate as evidenced by 13C and 15N solid-state nuclear magnetic resonance spectroscopy studies. On the basis of these results, we examined the performance of MOF-808-Gly in simulated coal flue gas conditions and found that it is possible to capture and release CO2 by vacuum swing adsorption. MOF-808-Gly was cycled at least 80 times with full retention of performance. This study significantly advances our understanding of CO2 chemistry in MOFs by revealing how strongly bound amine moieties to the MOF backbone create the chemistry and environment within the pores, leading to the binding and release of CO2 under mild conditions without application of heat.

Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer.

INTRODUCTION: Cisplatin and gemcitabine (CisGem) are standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomised Phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem. METHODS: Patients with advanced BTC received CisGem; arm A included selumetinib every day, arm B: selumetinib, days 1-5, 8-19 each cycle. Arm C received CisGem alone. Selumetinib was dosed at 75 mg BID but amended to 50 mg BID due to toxicity. RESULTS: In all, 51 participants were evaluable for response. No significant difference was seen in mean change in tumour size at 10 weeks between arms A and C (-7.8% vs -12.8%, P = 0.54) or arms B and C (-15% vs -12.8%, P = 0.78). There was no difference in median progression-free survival (6.0, 7.0, 6.3 months, P > 0.95) or overall survival (11.7, 11.7, 12.8 months, P = 0.70) for arms A, B and C, respectively. More participants experienced grade 3-4 toxicities in selumetinib-containing arms. More participants in arm A required chemotherapy dose reductions (P = 0.01) with lower chemotherapy dose intensity during the first 10 weeks. CONCLUSION: Adding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC.

Capturing the value of vaccination: impact of vaccine-preventable disease on hospitalization.

Evidence from epidemiological studies suggests that vaccine-preventable disease (VPD) such as influenza or herpes zoster contribute significantly to the increased risk of older adults for cardiovascular, cerebrovascular, neurological, and renal complications in the period after illnesses. However, since the period of elevated risk can persist well beyond the duration of the acute illness, the connection is not always recognized. To obtain insights into the relationship between diagnoses for vaccine-preventable disease and for other conditions, we analyzed principal and secondary diagnoses for 3,127,768 inpatient admissions of adults 50 years and older in the United States, using medical insurance claims drawn from the IBM® MarketScan® Research Databases (Marketscan). The Marketscan data indicated that overall, 3.1% of these hospitalizations had a principal diagnosis of VPD with variation by month of admission, and age. However, hospitalizations with a principal non-VPD diagnosis but secondary VPD diagnoses were 2.8 times more frequent, with particularly high rates in those whose principal diagnoses were non-VPD respiratory or circulatory disease. Hospitalized patients with a secondary VPD diagnosis tended to have poorer discharge outcomes, and longer length of stay in comparison to hospitalized patients without a secondary VPD diagnosis. In total, these data are consistent with suggestions that VPDs play a significant and potentially under-estimated role in hospitalization and outcomes, which may be potentially preventable by improved vaccination coverage.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. MATERIALS AND METHODS: ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. RESULTS: Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. CONCLUSION: This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. IMPLICATIONS FOR PRACTICE: In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations.

OBJECTIVE: Cerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition. METHODS: A prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography. RESULTS: Cerebellar pathology was confined to lobules I-V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology. CONCLUSIONS: Focal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

The financial impact of cancer care on renal cancer patients.

INTRODUCTION Advances in novel treatment options may render renal cell cancer (RCC) patients susceptible to the financial toxicity (FT) of cancer treatment, and the factors associated with FT are unknown. MATERIALS AND METHODS: Eligible patients were ≥ 18 years old and had a diagnosis of stage IV RCC for at least 3 months. Patients were recruited from Princess Margaret Cancer Centre and Sunnybrook Odette Cancer Centre (Toronto, Canada). FT was assessed using the validated Comprehensive Score for Financial Toxicity (COST) instrument, a 12-question survey scored from 0-44, with lower scores reflecting worse FT. Patient and treatment characteristics, out-of-pocket costs (OOP) and private insurance coverage (PIC) were collected. Factors associated with worse FT (COST score < 21) were determined. RESULTS: Sixty-five patients were approached and 80% agreed to participate (n = 52). The median age was 62 (44-88); 20% were female (n = 10); 43% were age ≥ 65 (n = 22); 63% were Caucasian (n = 31). Median COST score was 20.5 (3-44). Factors associated with worse FT were age < 65 (OR 9.5, p = 0.007), high OOP (OR 4.4, p = 0.04) and receiving treatment off clinical trial (in comparison to being on surveillance or on clinical trial) (OR 5.9, p = 0.03), when adjusting for other factors in multivariable logistic regression. However, there was no correlation between annual income or PIC and FT. CONCLUSION: Financial toxicity in the RCC population is more significant in younger patients and those on treatment outside of a clinical trial. Financial aid should be offered to these at-risk patients to optimize adherence to life prolonging RCC treatments.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples.

BACKGROUND: An increasing number of anti-cancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Successful use of these therapies is dependent on the presence or absence of somatic mutations within the patient's tumor that can confer clinical efficacy or drug resistance. METHODS: The aim of our study was to determine the type, frequency, overlap and functional proteomic effects of potentially targetable recurrent somatic hotspot mutations in 47 cancer-related genes in multiple disease sites that could be potential therapeutic targets using currently available agents or agents in clinical development. RESULTS: Using MassArray technology, of the 1300 patient tumors analysed 571 (43.9%) had at least one somatic mutation. Mutations were identified in 30 different genes. KRAS (16.5%), PIK3CA (13.6%) and BRAF (3.8%) were the most frequently mutated genes. Prostate (10.8%) had the lowest number of somatic mutations identified, while no mutations were identified in sarcoma. Ocular melanoma (90.6%), endometrial (72.4%) and colorectal (66.4%) tumors had the highest number of mutations. We noted high concordance between mutations in different parts of the tumor (94%) and matched primary and metastatic samples (90%). KRAS and BRAF mutations were mutually exclusive. Mutation co-occurrence involved mainly PIK3CA and PTPN11, and PTPN11 and APC. Reverse Phase Protein Array (RPPA) analysis demonstrated that PI3K and MAPK signalling pathways were more altered in tumors with mutations compared to wild type tumors. CONCLUSIONS: Hotspot mutational profiling is a sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular based therapeutics for treatment of cancer, and could potentially be of use in identifying novel opportunities for genotype-driven clinical trials.

NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121).

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients ≥18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma, gallbladder or ampullary cancer); randomized (1:1) to NUC-1031 (725 mg/m2)/cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2)/cisplatin (25 mg/m2), on days 1/8, Q21-days. Primary objectives are overall survival and objective response rate. Secondary objectives: progression-free survival, safety, pharmacokinetics, patient-reported quality of life and correlative studies. (Investigational new drug (IND) number: 139058, European Clinical Trials database: EudraCT Number 2019-001025-28, ClinicalTrials.gov identifier: NCT04163900).

Patient-reported symptoms following diagnosis in esophagus cancer patients treated with palliative intent.

The majority of patients with esophagus cancer have advanced-stage disease without curative options. For these patients, treatment is focused on improving symptoms and quality of life. Despite this, little work has been done to quantify symptom burden for incurable patients. We describe symptoms using the Edmonton Symptom Assessment System (ESAS) among esophagus cancer patients treated for incurable disease. This retrospective cohort study linked administrative datasets to prospectively collected ESAS data of non-curatively treated adult esophagus cancer patients diagnosed between January 1, 2009 and September 30, 2016. ESAS measures nine common cancer-related symptoms: anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. Frequency of severe symptoms (score ≥ 7/10) was described by month for the 6 months from diagnosis for all patients and by treatment type (chemotherapy alone, radiotherapy alone, both chemotherapy and radiotherapy, and best supportive care). A sensitivity analysis limited to patients who survived at least 6 months was performed to assess robustness of the results to proximity to death and resulting variation in follow-up time. Among 2,989 esophagus cancer patients diagnosed during the study period and meeting inclusion criteria, 2,103 reported at least one ESAS assessment in the 6 months following diagnosis and comprised the final cohort. Patients reported a median of three (IQR 2-7) ESAS assessments in the study period. Median survival was 7.6 (IQR 4.1-13.7) months. Severe lack of appetite (53.1%), tiredness (51.1%), and impaired well-being (42.7%) were the most commonly reported symptoms. Severe symptoms persisted throughout the 6 months after the diagnosis. Subgroup analysis by treatment showed no worsening of symptoms over time in those treated by either chemotherapy alone, or both chemotherapy and radiation. Results followed a similar pattern on sensitivity analysis. Patients diagnosed with incurable esophagus cancer experience considerable symptom burden in the first 6 months after diagnosis and the frequency of severe symptoms remains high throughout this period. Patients with this disease require early palliative care and psychosocial support upon diagnosis and support throughout the course of their cancer journey.

Excess all-cause mortality during the COVID-19 pandemic in Europe - preliminary pooled estimates from the EuroMOMO network, March to April 2020.

A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.

The Impact of Brain Metastases and Associated Neurocognitive Aspects on Health Utility Scores in EGFR Mutated and ALK Rearranged NSCLC: A Real World Evidence Analysis.

BACKGROUND: In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health-related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses. MATERIALS AND METHODS: In a prospective observational cohort study (2014-2016), outpatients with stage IV lung cancer completed demographic and EQ-5D-3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; regression analyses identified factors that were associated with HUS. A subset of patients prospectively completed neurocognitive function (NCF) tests and/or the FACT-brain (FACT-Br) questionnaire, which were then correlated with HUS (Spearman coefficients; regression analyses). RESULTS: Of 519 patients with 1,686 EQ-5D-3L-derived HUS, 94 (18%) completed NCF tests and 107 (21%) completed FACT-Br; 301 (58%) never developed BM, 24 (5%) developed first BM during study period, and 194 (37%) had BM at study entry. The sample was enriched (46%) for EGFR mutations (EGFRm) and ALK-rearrangements (ALKr). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFRm/ALKr (p < .0001), no prior radiation for extracranial disease (p < .001), and both intracranial (p = .002) and extracranial disease control (p < .01). HUS correlated with multiple elements of the FACT-Br and tests of NCF. CONCLUSION: Having BM in lung cancer is not associated with inferior HUS in a population enriched for EGFRm and ALKr. Patients exhibiting disease control and those with oncogene-addicted tumors have superior HUS. IMPLICATIONS FOR PRACTICE: In the setting of EGFR mutations or ALK rearrangement non-small cell lung cancer (NSCLC), a diagnosis of brain metastases no longer consigns the patient to an inferior health state suggesting that new economic analyses in NSCLC are needed in the era of targeted therapies. Additionally, the EQ-5D questionnaire is associated with measures of health-related quality of life and neurocognitive scores suggesting this tool should be further explored in prospective clinical studies.

Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations.

OBJECTIVES: This study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population. METHODS: Demographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996-2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion. RESULTS: The mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients). CONCLUSIONS AND RELEVANCE: This study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case-control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.ResultsInfluenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): -6.3 to 32) against all influenza; -16.4% (95% CI: -59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2-17 year olds, LAIV4 aVE was 26.9% (95% CI: -32.6 to 59.7) against all influenza; -75.5% (95% CI: -289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: -63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15-24 year olds.ConclusionsOverall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Reversible catalytic dehydrogenation of alcohols for energy storage.

Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels.