The cell type-specific ER membrane protein UGS148 is not essential in mice.

Genomes of higher eukaryotes encode many uncharacterized proteins, and the functions of these proteins cannot be predicted from the primary sequences due to a lack of conserved functional domains. In this study, we focused on a poorly characterized protein UGS148 that is highly expressed in a specialized cell type called tanycytes that line the ventral wall of the third ventricle in the hypothalamus. Immunostaining of UGS148 revealed the fine morphology of tanycytes with highly branched apical ER membranes. Immunoprecipitation revealed that UGS148 associated with mitochondrial ATPase at least in vitro, and ER and mitochondrial signals occasionally overlapped in tanycytes. Mutant mice lacking UGS148 did not exhibit overt phenotypes, suggesting that UGS148 was not essential in mice reared under normal laboratory conditions. We also found that RNA probes that were predicted to uniquely detect UGS148 mRNA cross-reacted with uncharacterized RNAs, highlighting the importance of experimental validation of the specificity of probes during the hybridization-based study of RNA localization.

Body weight loss as a prognostic and predictive factor in previously treated patients with metastatic gastric cancer: post hoc analyses of the randomized phase III TAGS trial.

BACKGROUND: Body weight loss (BWL) is a negative prognostic factor in metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). In the phase III TAGS study, trifluridine/tipiracil improved survival versus placebo in third- or later-line mGC/GEJC. These retrospective analyses examined the association of early BWL with survival outcomes in TAGS. METHODS: Efficacy and safety were assessed in patients who experienced < 3% or ≥ 3% BWL from treatment start until day 1 of cycle 2 (early BWL). The effect of early BWL on overall survival (OS) was assessed by univariate and multivariate analyses. RESULTS: Body weight data were available for 451 of 507 (89%) patients in TAGS. In the trifluridine/tipiracil and placebo arms, respectively, 74% (224/304) and 65% (95/147) experienced < 3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥ 3% BWL at cycle 1 end. Median OS was longer in < 3% BWL versus ≥ 3% BWL subgroups (6.5 vs 4.9 months for trifluridine/tipiracil; 6.0 vs 2.5 months for placebo). In univariate analyses, an unadjusted HR of 0.58 (95% CI, 0.46-0.73) for the < 3% vs ≥ 3% BWL subgroup indicated a strong prognostic effect of early BWL. Multivariate analyses confirmed early BWL as both prognostic (P < 0.0001) and predictive (interaction P = 0.0003) for OS. Similar results were obtained for progression-free survival. Any-cause grade ≥ 3 adverse events were reported in 77% and 82% of trifluridine/tipiracil-treated and 45% and 67% of placebo-treated patients with < 3% and ≥ 3% BWL, respectively. CONCLUSIONS: In TAGS, early BWL was a strong negative prognostic factor for OS in patients with mGC/GEJC receiving third- or later-line treatment.

The Effect of Shiatsu Therapy on Sleep Quality in Patients With Low Back Pain: A Secondary Analysis.

The aim of this study is to investigate the efficacy of shiatsu therapy for chronic low back pain and sleep disturbance. We conducted a secondary analysis of the randomized trial at a large academic hospital in Tokyo. Patients with chronic low back pain were included. Patients were randomly assigned to either shiatsu therapy in addition to standard care or standard care only by computer randomization. Our primary outcome was improvement of the global Pittsburgh Sleep Quality Index (PSQI) score, and the secondary outcomes were improvement in each component of the PSQI at weeks 4 and 8. We included a total of 59 patients. The mean age was 67.8 (SD: 13.5) years, and 21 patients (35.6%) were male. The global PSQI scores improved in the intervention group at week 4 (adjusted ß coefficient: 1.16, 95% confidence interval: 0.10-2.21) and week 8 (adjusted ß coefficient: 1.82, 95% confidence interval: 0.74-2.90). In terms of each component of the PSQI, sleep efficiency (component 4) and sleep disturbance (component 5) were improved, but use of sleep medication (component 5) worsened in the intervention group compared with the control group in several models. Shiatsu therapy in addition to standard therapy for chronic low back pain may improve sleep quality after intervention.

The effectiveness of controlled ovarian stimulation with tamoxifen for patients with estrogen-sensitive breast cancer: A systematic review and meta-analysis.

Purpose: Tamoxifen is used for the suppression of estrogen-sensitive tumor recurrence in oocyte retrieval cycles. This meta-analysis aimed to evaluate the quality of controlled ovarian stimulation (COS) with co-administration of gonadotropins and tamoxifen (COS with tamoxifen). Methods: PubMed, Embase, and Cochrane Library were searched for articles on October 30, 2022. The authors included studies comparing COS with tamoxifen and COS with gonadotropins and letrozole (COS with letrozole) or gonadotropin only (COS with gonadotropin only) for fertility preservation in patients with breast cancer. The main outcome measures were the COS quality, total number of retrieved oocytes (TOR), total number of mature oocytes (TMO), and peak estradiol levels (PEL). Results: Four studies (348 patients, two randomized controlled trials, and two cohort studies) were included in our meta-analysis. There was no significant difference in TOR (95% CI, [-3.84, 2.90]) and TMO (95% CI, [-2.20, 2.64]) between COS with tamoxifen and COS with letrozole. There was also no difference in TOR (95% CI, [-6.14, 1.86]) between COS with tamoxifen and COS with gonadotropin only. Statistically significant decrease was observed in PEL during COS with letrozole compared with tamoxifen (95% CI, [1414.4, 4953.7]). Conclusions: The quality did not differ between COS with tamoxifen and COS with letrozole or gonadotropin only.

Interpretation of the X-Ray Emission Spectra of Liquid Water through Temperature and Isotope Dependence.

The interpretation of x-ray emission spectroscopy (XES) spectra in terms of their sensitivity to the hydrogen bonding and the consequent microheterogeneity in liquid water has been debated over a decade. To shed a light on this problem, we report the theoretical reproduction of the debated 1b_{1} peaks observed in the XES spectra of liquid water using semiclassical Kramers-Heisenberg formula. The essence of the temperature and isotope dependence of the 1b_{1} double peaks is explained by molecular dynamics simulations including full vibrational (O─H stretching, bending, and) modes, rotational combined with the density functional theory and core-hole induced dynamics. Some inconsistencies exist with the experimental XES profile, which illustrates the need to employ a more precise theoretical calculations for both geometry sampling and electronic structure using a more sophisticated procedure.

A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations.

PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the PTEN gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline PTEN mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations.

Signaling paths control growth and activities inside cells. Overactivity in these paths can encourage many types of cancers to develop. Tumor suppressor proteins can inhibit cell signals that promote cancer. This protection can be lost if there are errors in any gene coding for a tumor suppressor protein. We are carrying out a clinical study to test TAS-117, a potential new oral medicine, in people who have solid tumors and whose cells have changes in their genes that inactivate a tumor suppressor protein called PTEN. TAS-117 targets part of a signaling path that may be overactive due to loss of PTEN activity. In early research, TAS-117 has shown promising activity against certain tumor types. Our trial will explore if TAS-117 can provide a new treatment for rare forms of cancer where genetic changes have led to a loss of PTEN activity. Clinical Trial Registration: NCT04770246 (ClinicalTrials.gov).

Impact of childbirth history on dense breast in mammographic screening: a cross-sectional study.

BACKGROUND: The evaluation of breast density is important, because dense breast has been shown to be associated with increased risk of breast cancer and a greater risk of a false-negative diagnostic performance due to masking a tumor. Although the relationship between parity and dense breast is under investigation, conclusive evidence is lacking. We aimed to investigate whether parity affects breast density. METHODS: The study design is a cross-sectional study. The subjects are healthy Japanese women who underwent opportunistic mammographic screening at the center for preventive medicine at a single institution from January 2016 to December 2018. Clinical characteristics and lifestyle factors were obtained from questionnaires. Breast density was categorized into 4 groups, namely, almost entirely fatty dense, scattered fibroglandular dense, heterogeneously dense, and extremely dense, according to the Breast Imaging Reporting and Data System. Heterogeneously and extremely dense were considered collectively as dense breast. Multivariate logistic regression analysis was conducted to investigate the relationship between parity and dense breast among premenopausal and postmenopausal women separately. RESULTS: 7612 premenopausal and 9252 postmenopausal women were investigated. Dense breast was shown in 62.6% of nulliparity, 57.3% of single parity, 47.3% of two parity, 37.6% of more than two parity among premenopausal women, and in 41.6% of nulliparity, 31.1% of single parity, 19.3% of two parity, 10.1% of more than two parity among postmenopausal women. For premenopausal women, two parity, single parity and nulliparity showed a higher risk for dense breast with statistically significance (Odds Ratio (OR) adjusted for potential confounding factors: 1.458 (95% Confidence interval (CI); 1.123-1.894), 2.349 (95%CI; 1.801-3.064), 3.222 (95%CI; 2.500-4.151), respectively), compared with more than two parity. For postmenopausal women, two parity, single parity and nulliparity had a higher risk (OR: 1.849 (95%CI; 1.479-2.312), 3.023 (95%CI; 2.385-3.830), 4.954 (95%CI; 3.975-6.174), respectively) with statistically significance, compared with more than two parity. CONCLUSIONS: Parity showed an inverse trend of having dense breast among both premenopausal and postmenopausal women. In particular, nulliparous women need to recognize their higher risk of dense breast. In the future, the declining fertility rate may affect the prevalence of dense breast in the world.

Knowledge, attitude, practice and perceived barriers of natural disaster preparedness among Nepalese immigrants residing in Japan.

BACKGROUND: Natural disasters have increased during the last several decades all over the world. Due to its geographical and climate conditions, Japan has long been vulnerable to several natural disasters. Coping with disasters is a major challenge overall and even harder for foreigners residing in Japan. Thus, the objective of this study was to examine the perceived knowledge, attitude, practice and perceived barriers of disaster preparedness among Nepalese immigrants in Japan. METHODS: A cross-sectional study was conducted among Nepalese immigrants residing in Japan with an online survey questionnaire. The questionnaire was validated and then administered. The participants were recruited via Facebook for this survey. Bivariable and multivariable logistic regression analyses were conducted to examine the factors associated with the perceived knowledge, attitude and practice of Nepalese immigrants regarding disaster preparedness. RESULTS: A total of 404 respondents were analyzed in this study and among them two-third were male. We found that the mean score of disaster preparedness practice was lowest than the knowledge and attitude (mean [Formula: see text] = 15.86 [Formula: see text] 5.52) as evidenced by the majority of the participants not being prepared for disaster situations and a limited proportion had ever taken necessary natural disaster preparedness measures. Japanese language was identified as the major barrier in assessing the knowledge, attitude and practice regarding disaster preparedness and was significantly associated with the knowledge level of disaster preparedness after adjusting for some socio-demographic covariates. (aOR: 1.84, 95% CI: (1.04 - 3.25)). CONCLUSIONS: This study observed that the perceived knowledge and practices regarding natural disasters are very poor while barriers to access these are substantial among Nepalese immigrants in Japan. As Japanese language was identified as a major barrier, the availability of language translation services in every health care sector also in the government offices of Japan might encourage people to learn more about disaster preparedness.

Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.

Interaction of cyclic naphthalene diimide derivatives (cNDIs), 1-4, with TA-core and c-myc as G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that 1-4 has 106 M-1 order of binding affinity with the following order: 1 > 4 > 2 > 3 under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by 4, which is in agreement with the result of PCR stop assay and the stabilization effect for 1-3 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 µM of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of ΔH/ΔG, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.

Cost-effectiveness analysis for HbA1c test intervals to screen patients with type 2 diabetes based on risk stratification.

BACKGROUND: The best HbA1c test interval strategy for detecting new type 2 diabetes mellitus (T2DM) cases in healthy individuals should be determined with consideration of HbA1c test characteristics, risk stratification towards T2DM and cost effectiveness. METHODS: State transition models were constructed to investigate the optimal screening interval for new cases of T2DM among each age- and BMI-stratified health individuals. Age was stratified into 30-44-, 45-59-, and 60-74-year-old age groups, and BMI was also stratified into underweight, normal, overweight and obesity. In each model, different HbA1c test intervals were evaluated with respect to the incremental cost-effectiveness ratio (ICER) and costs per quality-adjusted life year (QALY). Annual intervals (Japanese current strategy), every 3 years (recommendations in US and UK) and intervals which are tailored to each risk stratification group were compared. All model parameters, including costs for screening and treatment, rates for complications and mortality and utilities, were taken from published studies. The willingness-to-pay threshold in the cost-effectiveness analysis was set to US $50,000/QALY. RESULTS: The HbA1c test interval for detecting T2DM in healthy individuals varies by age and BMI. Three-year intervals were the most cost effective in obesity at all ages-30-44: $15,034/QALY, 45-59: $11,849/QALY, 60-74: $8685/QALY-compared with the other two interval strategies. The three-year interval was also the most cost effective in the 60-74-year-old age groups-underweight: $11,377/QALY, normal: $18,123/QALY, overweight: $12,537/QALY-and in the overweight 45-59-year-old group; $18,918/QALY. In other groups, the screening interval for detecting T2DM was found to be longer than 3 years, as previously reported. Annual screenings were dominated in many groups with low BMI and in younger age groups. Based on the probability distribution of the ICER, results were consistent among any groups. CONCLUSIONS: The three-year screening interval was optimal among elderly at all ages, the obesity at all ages and the overweight in 45-59-year-old group. For those sin the low-BMI and younger age groups, the optimal HbA1c test interval could be longer than 3 years. Annual screening to detect T2DM was not cost effective and should not be applied in any population.

Differences in aggressive treatments during the actively dying phase in patients with cancer and heart disease: an exploratory study using the sampling dataset of the National Database of Health Insurance Claims.

Despite the recent attention given to palliative care for patients with heart disease, data about the treatments in their actively dying phase are not sufficiently elaborated. In this study, we used the sampling dataset of a national database to compare the aggressive treatments performed in patients with cancer and those with heart disease. We only included patients deceased in January or July from 2011 to 2015, using the Diagnosis Procedure Combination sampling dataset of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Patients who were discharged within the first 10 days of each month were excluded. We explored and compared aggressive treatments such as cardiopulmonary resuscitation and intensive care utilization, performed within seven days before death in cancer patients. We used 10,637 (0.4% of the dataset) deceased target population (40.0% female), with 7844 (73.7%) and 2793 (26.3%) being the proportion of cancer and heart disease patients, respectively. Aggressive treatments and procedures such as cardiopulmonary resuscitation (18.4%), intensive care utilization (5.4%), use of inotropes (43.4%), use of respirators (29.1%), and dialysis (4.5%) were frequently observed in heart disease patients. These associations remained after adjusting for age, sex, and disease severity. This study indicates the possible use of an NDB sampling dataset to evaluate the aggressive treatments and procedures in the actively dying phase in both heart disease and cancer patients. Our results showed the differences in aggressive treatment strategies in the actively dying phase between patients with cancer and those with heart disease.

Psychological impact of the state of emergency over COVID-19 for non-permanent workers: a Nationwide follow-up study in Japan.

BACKGROUND: The outbreak of COVID-19 has caused mental health problems and increased unemployment due to the economic recession. This survey aimed to assess the psychological impact of the state of emergency. We estimated changes in mental health, quality of life, and unemployment experience for general workers during the first COVID-19 outbreak in Japan. METHODS: We conducted a nationwide follow-up study. During the periods of March 26 to April 6, 2020 and June 26 to July 2, 2020, we used the internet to survey general workers aged 15 to 59 years in Japan. The questionnaire items covered employment status and socioeconomic factors, and we used the Center for Epidemiologic Studies Depression Scale (CES-D) and EQ-5D-5L to assess depression and health-related quality of life (HR-QOL), respectively. The differences in outcomes of permanent and non-permanent workers were analyzed using propensity score analysis. A multiple linear regression analysis was performed to examine the relationship between unemployment and CES-D scores. RESULTS: We included 2351 subjects in the analysis. Changes in both CES-D scores and utility were not significantly different between the two groups. However, a significant difference was found regarding the rate of unemployment, which was associated with higher CES-D scores. CONCLUSIONS: The present study demonstrated that the mental health of non-permanent workers was not negatively affected following the state of emergency due to COVID-19 in Japan. Unemployment is an important factor that influences the mental health of general workers.

Differences in clinical knowledge levels between residents in two post-graduate rotation programmes in Japan.

BACKGROUND: In Japan, between 2010 and 2020, there were two post-graduate training curricula for post-graduate medical education, as follows: comprehensive rotation programmes (CRPs), which require rotation in at least seven clinical departments; and limited rotation programmes (LRPs), which require rotation in fewer clinical departments. The curriculum that should be used for standardized Japanese post-graduate training has long been debated. Multiple studies show that post-graduate trainees who trained with CRPs were more satisfied and confident and gained more clinical experience than those who trained with LRPs. However, a comparison of objective measurements of the clinical knowledge of Japanese post-graduate trainees has not been reported. The aim of this study is to objectively measure and compare the clinical knowledge of trainees in CRPs and LRPs using a component of the Professional and Linguistic Assessment Board test (PLAB test). METHODS: A nationwide cross-sectional study was conducted in February and March 2020. Post-graduate trainees who graduated from medical school were voluntarily recruited from general hospitals in Japan. To objectively measure the trainees' basic clinical knowledge, the PLAB test was adapted from the UK. The cut-off point was set at 63%, as recommended by the UK General Medical Council. A statistical analysis was conducted to determine whether post-graduate programme differences contributed to the trainees' test scores. RESULTS: Twenty-two facilities volunteered to participate after recruitment, and 97 trainees from 19 facilities participated in the study. Thirty-one participants (32%) were in a CRP, and 66 participants (68%) were in an LRP. According to multiple logistic regression, the adjusted odds ratio of CRP trainees being in the high-scoring group was 5.16 (95% CI: 1.28-20.73, p<0.05). Mean differences in the scores in paediatrics, mental health and neurology were statistically higher among CRP trainees than LRP trainees. CONCLUSION: Post-graduate trainees who were in a CRP had better basic clinical competence knowledge (PLAB test) scores and performed better when tested in a wider range of subspecialties. Not only exam performance but also clinical performance and the longitudinal trend of trainees' competency in post-graduate medical training should be evaluated in future studies.

Msx1 Heterozygosity in Mice Enhances Susceptibility to Phenytoin-Induced Hypoxic Stress Causing Cleft Palate.

OBJECTIVE: Cleft palate is among the most frequent congenital defects in humans. While gene-environment multifactorial threshold models have been proposed to explain this cleft palate formation, only a few experimental models have verified this theory. This study aimed to clarify whether gene-environment interaction can cause cleft palate through a combination of specific genetic and environmental factors. METHODS: Msx1 heterozygosity in mice (Msx1+/-) was selected as a genetic factor since human MSX1 gene mutations may cause nonsyndromic cleft palate. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin, a known arrhythmia inducer, during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palatal state. RESULTS: Phenytoin administration downregulated cell proliferation in palatal processes in both wild-type and Msx1+/- embryos. Bone morphogenetic protein 4 (Bmp4) expression was slightly downregulated in the anterior palatal process of Msx1+/- embryos. Although Msx1+/- embryos do not show cleft palate under normal conditions, phenytoin administration induced a significantly higher incidence of cleft palate in Msx1+/- embryos compared to wild-type littermates. CONCLUSION: Our data suggest that cleft palate may occur because of the additive effects of Bmp4 downregulation as a result of Msx1 heterozygosity and decreased cell proliferation upon hypoxic stress. Human carriers of MSX1 mutations may have to take more precautions during pregnancy to avoid exposure to environmental risks.

Changes in tonsillolith characteristics detected in a follow-up CT study.

BACKGROUND: Tonsilloliths are related clinically to halitosis and tonsillar abscess. However, the dynamics of tonsilloliths over time are unknown. The aim of the study was to evaluate change in the characteristics of tonsilloliths in a time-dependent fashion by follow-up computed tomography (CT). METHODS: Tonsilloliths were analyzed in 326 CT scan pair sets of initial and at least two follow-up CT examinations of patients with whole palatine tonsils and various diseases of the oral and maxillofacial regions. RESULTS: Over the follow-up period, 12.1% of tonsilloliths disappeared. Approximately 26.1% of tonsilloliths changed in size during follow-up, mostly increasing in size. In tonsilloliths that showed enlargement, the mean (± standard deviation) growth rate was 0.61 ± 0.41 mm per year. Approximately 37.3% of tonsilloliths changed position during the follow-up period; of these, movement was toward the respiratory tract in 92% at a mean rate of - 1.38 ± 1.59 mm per year. The calcification levels of almost all tonsilloliths showed dynamic change: HU number increased in 84.3% and decreased in 12.7% of tonsilloliths over the follow-up period. The mean rate of HU increase was 63.8 ± 96.3 HU/year, and the mean rate of HU decrease was - 38.4 ± 66.8 HU/year. CONCLUSIONS: The calcification levels of all tonsilloliths showed dynamic fluctuation, and a tendency for excretion of tonsilloliths from the body. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase which functions to remove foreign matter.

Probable usual interstitial pneumonia pattern on chest CT: is it sufficient for a diagnosis of idiopathic pulmonary fibrosis?

Recent studies have suggested that in patients with an idiopathic interstitial pneumonia (IIP), a probable usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT) is sufficient to diagnose idiopathic pulmonary fibrosis (IPF) without histopathology.We retrospectively compared the prognosis and time to first acute exacerbation (AE) in IIP patients with a UIP and a probable UIP pattern on initial chest CT.One hundred and sixty IIP patients with a UIP pattern and 242 with a probable UIP pattern were identified. Probable UIP pattern was independently associated with longer survival time (adjusted hazard ratio 0.713, 95% CI 0.536-0.950; p=0.021) and time to first AE (adjusted hazard ratio 0.580, 95% CI 0.389-0.866; p=0.008). In subjects with a probable UIP pattern who underwent surgical lung biopsy, the probability of a histopathological UIP pattern was 83%. After multidisciplinary discussion and the inclusion of longitudinal behaviour, a diagnosis of IPF was made in 66% of cases. In IPF patients, survival time and time to first AE were not associated with CT pattern. Among subjects with a probable UIP pattern, compared to non-IPF patients, survival time and time to first AE were shorter in IPF patients.In conclusion, IIP patients with a probable UIP pattern on initial chest CT had a better prognosis and longer time to first AE than those with a UIP pattern. However, when baseline data and longitudinal behaviour provided a final diagnosis of IPF, CT pattern was not associated with these outcomes. This suggests diagnostic heterogeneity among patients with a probable UIP pattern.

Prognostic Significance of Hyponatremia in Acute Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hyponatremia is a common electrolyte disorder in patients with stroke, which leads to various fatal complications. We performed a systematic review and meta-analysis to investigate the outcomes of acute stroke patients with hyponatremia. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library databases for relevant literature in English published up to March 2020. Two review authors independently screened and selected the studies by assessing the eligibility and validity based on the inclusion criteria. Mortality at 90 days was set as the primary end point, and in-hospital mortality and length of hospital stay were set as the secondary end points. We conducted the data synthesis and analyzed the outcomes by calculating the odds ratio (OR) and mean difference. RESULTS: Of 835 studies, 15 studies met the inclusion criteria (n = 10,745). The prevalence rate of stroke patients with hyponatremia was 7.0-59.2%. They had significantly higher 90-day mortality (OR, 1.73; 95% confidence interval (CI), 1.24-2.42) and longer length of hospital stay (mean difference, 10.68 days; 95% CI, 7.14-14.22) than patients without hyponatremia. Patients with hyponatremia had a higher tendency of in-hospital mortality than those without hyponatremia (OR, 1.61; 95% CI, 0.97-2.69). CONCLUSIONS: The development of hyponatremia in the clinical course of stroke is associated with higher short-term mortality and a longer hospital stay. Although the causal relationship is unclear, hyponatremia could be a significant predictor of poor outcomes after stroke.

The relationship between preference-based health-related quality of life and lifestyle behavior: a cross-sectional study on a community sample of adults who had undergone a health check-up.

BACKGROUND: Preference-based Health-Related Quality of Life (HRQL) is one of the most important indicators for calculating QALY (Quality-Adjusted Life Years) in a cost-effectiveness analysis. This study aimed to collect data on healthy individuals' HRQL based on the preferences of Japanese people who had undergone a comprehensive health check-up, and to examine the influence of relevant factors, such as blood biochemical data and lifestyle behavior. METHODS: We conducted a cross-sectional study targeting people who had undergone a comprehensive health check-up in 2015. Participants were asked to respond to a medical interview sheet. We then examined the utility value, as well as lifestyle habits such as alcohol intake, smoking, and exercise. HRQL was examined using EQ-5D-5L. Using a multiple regression analysis, we examined the influence of related factors, such as lifestyle and biochemical test data. RESULTS: We collected 2037 responses (mean age = 54.98 years; 55.0% female). The average preference-based health-related HRQL was 0.936 ± 0.087. A total of 1167 people (57.2%) responded that they were completely healthy. The biochemical test data that were recognized to correlate with HRQL were hemoglobin, total cholesterol, creatinine, all of which were weak (r = - 0.045-0.113). The results of multiple regression analysis showed that significant facts were: being female, age (≧70 year-old), drinking alcohol (sometimes), activity (very often), and lack of sleep. CONCLUSIONS: The HRQL of participants who had undergone a comprehensive health check-up was generally high, and only declined for those over 70 years of age. It is suggested that preference-based HRQL is related to physical activity, and that decrease of activity and lack of sleep leads to a decrease in HRQL.

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potential biomarker for monitoring the status of heart failure. However, the optimal monitoring interval of NT-proBNP is unknown. This study sought to investigate the minimal informative monitoring interval of NT-proBNP in patients with stable chronic heart failure. METHODS: This retrospective cohort study included patients who were admitted due to heart failure and subsequently followed with serial NT-proBNP measurements in a tertiary hospital. We analyzed NT-proBNP measured between six months after discharge and the earliest timepoint of: an alteration of medication regimen, readmission due to worsening of heart failure, or all-cause death. To distinguish progression of the disease from biological variability and measurement error, the signal-to-noise ratio method was applied with a random-effects model. RESULTS: In the 368 patients included, NT-proBNP was measured for a median 6 times. In the random-effects model, signal (progression of disease) exceeded noise (biological variability and measurement error) at 7.9 months (95% confidence interval [CI]: 5.1-9.6), while noise corresponded to a 61% increase from baseline. In stratified analysis using the AHEAD risk score, the minimal informative monitoring interval shortened as the risk score increased (0-1 point: 12.2 months [95%CI: 10.3-14.4]; 2-3 points: 8.0 months [95%CI: 6.8-9.7]; 4-5 points: 3.3 months [95%CI: 3.0-3.8]). CONCLUSIONS: In patients with stable chronic heart failure, the minimal informative monitoring interval of NT-proBNP measurement was 7.9 months in the current population, which varied with underlying risks. The optimal monitoring interval could be lengthened for patients at lower risks.

The impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis: A competing risk regression analysis.

While advanced age is a main prognostic factor in patients with tuberculosis, the factors that specifically affect tuberculosis-related death are unclear because elderly people are at a risk for other age-related lethal diseases. We aimed to assess the impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis. Elderly patients (≥65 years of age) admitted to our hospital for bacteriologically-diagnosed lung tuberculosis were included, and analyzed the influence of performance status on tuberculosis-related in-hospital death, with non-tuberculosis-related death as a competing risk. Forty and 19 of the 275 patients died from tuberculosis-related causes and non-tuberculosis-related causes, respectively. The tuberculosis-related death group had a greater number of patients with a poor performance status (defined as category 3 and 4 [HR 21.022; 95%CI 2.881-153.414; p = 0.003]), a lower serum albumin level (HR 0.179; 95%CI 0.090-0.359; p < 0.001) and a higher C-reactive protein level (HR1.076; 95%CI 1.026-1.127; p = 0.002). A multivariate competing risk regression analysis showed that a poor performance status (HR 7.311; 95%CI 1.005-53.181; p = 0.049) and low albumin level (HR 0.228; 95%CI 0.099-0.524); p = 0.001) significantly predicted tuberculosis-related death. Performance status can be a useful scale for predicting tuberculosis-related death among elderly patients with pulmonary tuberculosis.