Factors Associated with Improvement in Activities of Daily Living during Hospitalization: A Retrospective Study of Older Patients with Hip Fractures

Background In this study, we aimed to examine the changes in delirium during hospitalization of patients and its association with behavioral and psychological symptoms of dementia (BPSD), as well as improvements in activities of daily living (ADL). Methods A longitudinal, retrospective cohort study was conducted involving 83 older adults (≥65 years) with hip fractures. We collected Mini-Mental State Examination (MMSE) and Functional Independence Measure-motor domain (m-FIM) assessment results from the medical charts at two time points: baseline (first week of hospitalization) and pre-discharge (final week before discharge). Additionally, we collected data on delirium and BPSD at three points: baseline, week 2 post-admission, and pre-discharge. We performed univariate logistic regression analysis using changes in m-FIM scores as the dependent variable and MMSE and m-FIM scores at baseline and pre-discharge, along with delirium and BPSD subtypes at baseline, week 2 post-admission, and pre-discharge, as the explanatory variables. Finally, we performed a multivariate logistic regression analysis incorporating the significant variables from the univariate analysis to identify factors associated with ADL improvement during hospitalization. Results We observed significant correlations between ADL improvement during hospitalization and baseline m-FIM and MMSE scores, hypoactive delirium state, and BPSD subtype pre-discharge. Notably, all participants with hypoactive symptoms before discharge exhibited some subtype of delirium and BPSD at baseline. Conclusion Besides ADL ability and cognitive function at admission, the presence of hypoactive delirium and BPSD subtype before discharge may hinder ADL improvement during hospitalization

EGFR mutation and ALK fusion-positive non-small cell lung cancer: a multicenter prospective cohort study in Nagano Prefecture, Japan

Introduction. We prospectively examined current clinical practices in patients with inoperable epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion-positive (EGFR+ and ALK+, respectively) non-small cell lung cancer (NSCLC) in Nagano Prefecture, Japan.  Material and methods. The study population consisted of newly diagnosed patients with inoperable EGFR+ and ALK+ NSCLC in 14 hospitals in Nagano between May 2016 and March 2019. Both initial and subsequent treatment decisions were made at the discretion of the attending physician.  Results. A total of 281 patients with EGFR+ NSCLC (mean age, 74 years, 59.1% female) and 26 patients with ALK+ NSCLC (mean age, 66 years, 53.8% female) were included in the study. The study population consisted of 148/107/29/20/3 cases with performance status 0/1/2/3/4 and 6/2/31/194/75 cases with clinical stage I/II/III/IV/recurrence, respectively. First-line therapy with tyrosine kinase inhibitors was performed in 259 (92.2%) and 22 (84.6%) patients with EGFR+ and ALK+ NSCLC, respectively. The median overall survival rate was 41.2 months (95% CI 36.8–45.6 months) with EGFR+. It was not reached with ALK+ .  Conclusions. This observational analysis represents a valuable resource for evaluating the outcomes of treatment in patients with NSCLC

A multicenter randomized controlled trial to evaluate the efficacy and safety of nelfinavir in patients with mild COVID-19

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARS-CoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

高齢者のQOL向上を目指したライフレビュー活動の有効性に関する検討 : 無作為比較対照試験

広島大学(Hiroshima University)博士(保健学)Hygienedoctora

Natural History of Spongy State

1) One case of Inose-type of hepatocerebral disease was reported clinicopathologically. 2) The literature on spongy state of the gray matter of the nervous system is reviewed. Fischer's opinion that the spongy state is the end result of neuron loss is no longer accepted. The functional disturbances of Hortega's angio-glione are especially put forward nowadays. A historical review of neuropile spongy state stresses the enormous contribution of the German neuropathological school. Different authors have studied some particular features which a posteriori take a new signification: Spielmeyer has discovered the notion of glial insufficiency; Konowalow has put forward the glio-capillary intoxication; Scholz has considered the problems of dysoria and serous exsudation; von Braunmuhl has discussed the hydratation and deshydratation phenomena. Finally, Stochdorph has emphasized the importance of the main vascular territories. The ideas of Spielmeyer, Scholz, von Braunmuhl and Stochdorph remain highly and fundamentally valuable but must be associated together in order to obtain a dynamical conception of the way spongy state is produced. Every spongy state results from different factors: some of them are susceptible to predominate but very often they act together. According to the historical features we mentioned, it becomes evident that the facts revealed by the more recent developments of molecular biology represent only further progress and materialization of Hortega's angio-glione disturbances theory