Steroid therapy for patients with septic shock: A multicenter observational study conducted in Japan.

Objectives The Clinical Practice Guidelines for the Management of Sepsis and Septic Shock weakly recommend steroids for septic shock resistant to fluid resuscitation and vasopressors. This study aimed to describe the clinical practices for septic shock in the real world and to compare the association between the intermittent or continuous infusion of steroids and the prognosis. Methods This was a retrospective cohort study based on the AMOR-VENUS, in which Japanese intensive care unit (ICU) inpatients were enrolled between January and March 2018. Adult patients with sepsis who received vasopressors within 72 h of ICU admission were included. The patients were divided into non-steroid and steroid groups, which were further divided into intermittent and continuous infusion groups. The patient characteristics and details of the steroids are described. To investigate the association between intermittent or continuous infusion, shock reversal, and mortality, logistic regression analyses were performed after adjusting for possible confounding factors. Results A total of180 patients with septic shock from 18 ICUs were enrolled. The mean age was 69.6 (SD, 14.3) years. Sixty-three patients (35.0%) received steroids (26 intermittently, 37 continuously). In the steroid group, hydrocortisone was used in 85.7%, the median daily dose was 192 mg, and the steroids were administered within 6 h of initiating vasopressor in 71.4%. The adjusted odds ratios of shock reversal on the 7th day and the ICU mortality for continuous versus intermittent infusion were 1.90 (95%CI, 0.43-8.40) and 0.61 (0.10-3.85), respectively. Conclusions There was considerable variation in the criteria for the selection of patients and in the decision to use continuous or intermittent steroid infusion.

Japanese clinical practice patterns of rituximab treatment for minimal change disease in adults 2021: A web-based questionnaire survey of certified nephrologists.

BACKGROUND: In Japan, rituximab (RTX) for adult-onset frequently relapsing (FR)/steroid-dependent (SD) minimal change disease (MCD) is not explicitly reimbursed by insurance, and its standard regimen has not been established. METHODS: We conducted a cross-sectional web-based survey between November and December 2021. The participants were nephrologists certified by the Japanese Society of Nephrology and answered 7 items about RTX for adult MCD. Factors related to the experience of RTX administration at their facilities were estimated by generalized estimating equations. RESULTS: Of 380 respondents, 181 (47.6%) reported the experience of RTX use for adult MCD at their current facilities. Those who worked at university hospitals (vs. non-university hospitals, proportion difference 13.7%) and at facilities with frequent kidney biopsies (vs. 0 cases/year, 19.2% for 1-40 cases/year; 37.9% for 41-80 cases/year; 51.9% for ≥ 81 cases/year) used RTX more frequently. Of 181 respondents, 28 (15.5%) answered that there was no insurance coverage for RTX treatment. Of 327 respondents who had the opportunity to treat MCD, which was a possible indication for RTX, 178 (54.4%) indicated withholding of RTX administration. The most common reason was the cost due to lack of insurance coverage (141, 79.2%). Regarding RTX regimens for FR/SD MCD, introduction treatment with a single body surface area-based dose of 375 mg/m2 and maintenance treatment with a 6-month interval were the most common. CONCLUSION: This survey revealed the nephrologists' characteristics associated with RTX use, the barriers to RTX use, and the variation in the regimens for adult MCD in Japan.

Perspectives on the optimal timing of advance care planning among Japanese patients undergoing dialysis and clinicians: a cross-sectional study.

KEY MESSAGES: The majority of dialysis patients and clinicians favor early advance care planning in our sample. Yet, there is a disconnect: only 11% of patients discussed future care with their clinicians. Our findings indicate Japanese dialysis patients and clinicians support proactive advance care planning at or before dialysis initiation. BACKGROUND: Little is known about the optimal timing of discussions about advance care planning among dialysis patients and clinicians engaged in dialysis care. We aimed to explore the preferred timing for advance care planning and assess actual participation in advance care planning among dialysis patients and their clinicians. METHODS: A scenario-based survey on Japanese patients aged ≥65 years on dialysis and clinicians involved in their dialysis care was performed. Participants were asked if they would feel prepared to engage in advance care planning with their clinicians, offering a choice among four hypothetical stages within the illness trajectory, extending from the initiation of dialysis to a later phase characterized by the patient's extreme frailty. RESULTS: Overall, 181 patients and 128 clinicians participated in the study. Among these, 131 (72%) patients, and 84 (66%) clinicians indicated that they would prefer to initiate advance care planning around the time of dialysis initiation. Only 20 patients (11%) indicated that they had participated in advance care planning with at least one clinician, including 11 (6%) who indicated that they had discussed their preferences around life-sustaining treatments and 8 (4%) who had discussed their preferences around dialysis continuation. CONCLUSIONS: While fewer than 11% of patients undergoing dialysis and their clinicians enrolled in our study had participated in advance care planning, most indicated that they would be comfortable initiating the discussion around the time of dialysis initiation. These findings suggest untapped opportunities to engage patients in advance care planning early in the course of their dialysis.

Preference for anti-phospholipase A2 receptor antibody assay in patients with suspected membranous nephropathy: a survey study on medical practice after publication of Japanese Guidelines for Nephrotic Syndrome 2020.

BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test. METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation. RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation. CONCLUSION: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists.

BACKGROUND: Although rituximab (RTX) is recommended by kidney disease improving global outcomes as one of the standard therapies for primary membranous nephropathy (pMN), given the constraint of insurance coverage, it is not clear how the drug is used in Japan. METHODS: This cross-sectional study was conducted via a web-based survey between November and December 2021. The participants were certified nephrologists and recruited through convenience sampling. Experience with RTX for pMN was compared to experience with RTX for minimal change nephrotic syndrome (MCNS). Reasons for withholding RTX for pMN, even when it is indicated, were also investigated. Furthermore, the proportion difference in RTX experience was analyzed. RESULTS: Responses from 380 nephrologists across 278 facilities were analyzed. RTX was used for pMN by 83 (21.8%), which was less than the 181 (47.6%) who had used RTX for MCNS (ratio of proportions: 0.46). RTX use for pMN was more frequent in facilities performing 41-80 and 81 or more kidney biopsies annually (vs. none) and by physicians with experience in anti-PLA2R antibody measurement. RTX administration for pMN was covered by insurance for 56 (67.5%), was facility-paid for 10 (12.0%), and was copaid by patients for 6 (7.2%). The most common reason for withholding RTX for pMN was difficulty in ensuring financing (146, 79.3%). CONCLUSIONS: RTX use for pMN is less common than for MCNS but not infrequent. Treatment with RTX was more frequent in biopsy-intensive facilities, and it was fully paid by the facility or patient in one-fifth of cases.

Alternating current electromagnetic field exposure lessens intramyocellular lipid accumulation due to high-fat feeding via enhanced lipid metabolism in mice.

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption.

Translation and Validation Testing of the Constipation-Related Quality of Life Scale for Use in Japan.

Introduction Establishing a scale that can easily be used to appropriately measure the impact of constipation on the quality of life in Japan is a first step toward addressing this important health issue. We developed a Japanese language version of the Constipation-Related Quality of Life scale, which has 18 items and four subscales, and then subjected it to validation testing. Methods After translation according to a standardized and commonly used procedure, the Japanese version of the Constipation-Related Quality of Life scale was administered to people in an internet-based panel, in March 2023. The participants included 1,276 adults who had constipation (median age: 60 years, 690 {54.1%} males). The outcome measures included the Constipation-Related Quality of Life scale, the Constipation Scoring System (an index of constipation severity), and the Medical Outcomes Study (MOS) eight-item short form (a measure of generic health-related quality of life). Results Confirmatory factor analysis (four-factor model) indicated that all 18 Constipation-Related Quality of Life items had sufficiently high factor loadings (0.686-0.926). Internal consistency reliability was high (Cronbach's alpha: 0.86-0.94). Scores on the social impairment subscale and on the distress subscale of the Constipation-Related Quality of Life scale were significantly worse in the participants who had worse scores on the social functioning and mental health domains, respectively, of the MOS eight-item short form, which indicates good concurrent validity. Regarding criterion-based validity, the four subscale scores differed significantly among the four constipation-severity groups. The four subscale scores were also 1.16-4.53 times more sensitive than the MOS eight-item short form's mental component score to differences among the four constipation-severity groups (relative validity: 1.16-4.53), which indicates good discriminant validity. Conclusion The Japanese version of the Constipation-Related Quality of Life scale can be used with confidence in its factor structure, its concurrent, criterion-based, and discriminant validity, and its internal consistency reliability.

Poor Social Functioning: A Potentially Modifiable Risk Factor for Pneumonia in the Elderly.

Background Most risk factors for developing community-acquired pneumonia (CAP) are age-related and chronic medical conditions; modifying these factors can be challenging, especially in the elderly. Poor social functioning, however, has a negative impact on medical conditions but can be improved through interventions. Therefore, the social functioning domain of health-related quality of life (HRQOL) may be a modifiable risk factor for the development of CAP. This study investigated the association between poor social functioning and the incidence of CAP in elderly individuals. Methodology We conducted a retrospective cohort study using a dataset from 2018 to 2021, derived from an annual questionnaire-based survey of a cohort of community-dwelling people aged 75 years or older (the Sukagawa Study). The dataset included social functioning subscale scores of HRQOL obtained from the Eight-Item Short Form (SF-8) questionnaire. Health insurance claims data were matched with these HRQOL data. For each participant, the exposure (HRQOL) was measured, and outcomes (incidence of CAP) were observed yearly from 2018 through 2021. Results The four observation years had a total of 17,016 observation periods among 6,513 participants. The annual incidence rate of CAP was 0.90-1.77%. Lower social functioning was associated with a higher risk of CAP. Specifically, for each standard deviation difference in social functioning score, the adjusted rate ratio for CAP incidence was 1.26 (95% confidence interval (CI) = 1.08-1.48). In a subgroup analysis, the association between social functioning and CAP differed by sex (p = 0.037). Specifically, the adjusted rate ratio for CAP incidence was 1.41 (95% CI = 1.17-1.70) in men and 1.00 (95% CI = 0.76-1.35) in women. Conclusions Poor social functioning is an important risk factor for CAP in the elderly, especially in men. Interventions that improve social functioning may help to prevent CAP.

Association between inpatient education program for patients with pre-dialysis chronic kidney disease and new-onset cardiovascular disease after initiating dialysis.

BACKGROUND: The association between inpatient education programs (IEPs) for patients with pre-dialysis chronic kidney disease (CKD) and new-onset cardiovascular disease (CVD) after initiating dialysis is unclear. METHODS: We conducted a retrospective cohort study between January 1, 2011 and December 31, 2018, evaluating CKD patients who were divided into two groups based on whether or not they participated in IEPs. The primary outcome was a new-onset CVD event after initiating dialysis. Cumulative incidence function was used to describe new-onset CVD considering the competing outcome of death. Additionally, Cox proportional hazards models were used to estimate the hazard ratio of new-onset CVD between IEP and non-IEP groups. RESULTS: Of the 493 patients, 131 (26.6%) patients had participated in IEPs. The IEP group had a significantly longer duration of CKD management by nephrologists (median 142 vs. 115 days, P = 0.007), lower rate of emergency hospital admissions (9.9% vs. 27.1%, P < 0.001), better ability to perform activities of daily living (Grade J; 81.6% vs. 69.1%, P = 0.046), higher rate of pre-placement of permanent vascular access or peritoneal dialysis catheters (82.4% vs. 59.4%, P < 0.001), and a higher serum albumin level at the beginning of dialysis (3.5 ± 0.5 vs. 3.3 ± 0.6 g/dL, P < 0.001). The cumulative incidence of new-onset CVD at three years after initiating dialysis in the IEP and non-IEP groups was 16.9% and 22.5%, respectively. The hazard ratio for new-onset CVD after initiating dialysis in the IEP group was 0.63 (95% CI: 0.41-0.97, P = 0.036). CONCLUSION: IEPs were associated with a lower rate of new-onset CVD after initiating dialysis.

A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.

Longitudinal Association Between Social Isolation and COVID-19 Vaccine Uptake in Japanese Older Citizen: an Observational Study.

BACKGROUND: Social isolation is associated with decreased intent to receive vaccination against coronavirus disease 2019 (COVID-19); however, its association with COVID-19 vaccine uptake is unknown. OBJECTIVE: The present study aimed to determine the association between social isolation and subsequent COVID-19 vaccination using the data from a representative Japanese sample. DESIGN: Longitudinal observational study. PARTICIPANTS: Japanese citizens aged ≥ 65 years who participated in the Quality of Life in COVID-19 Era (QoLCoVE) study which began in March 2020. MAIN MEASURES: Social isolation was assessed in March 2020 using the abbreviated Lubben Social Network Scale, with a score of ≤ 11 indicating social isolation. To evaluate the relationship between social isolation at the baseline and COVID-19 vaccine uptake (including reservation for vaccine administration) between August and September 2021, we estimated adjusted risk ratios with 95% CIs using modified Poisson regression with adjustment for potential confounders. KEY RESULTS: A total of 921 participants met the inclusion criteria in the initial survey, of whom 720 (78.2%) completed the follow-up survey. Median age was 70 years (interquartile range: 66-72), and 329 (45.7%) participants were male. Twenty-one (16.5%) of 127 socially isolated participants, and 48 (8.1%) of 593 non-socially isolated participants did not receive the COVID-19 vaccine. Socially isolated participants were less likely to take COVID-19 vaccine than non-socially isolated participants (adjusted risk ratio 1.98, 95% CI: 1.18-3.32). CONCLUSIONS: Social isolation is associated with reduced COVID-19 vaccine uptake among older adults. To further promote COVID-19 vaccination in the older population, support for social isolation might be necessary.

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

Prehospital shock index predicts 24-h mortality in trauma patients with a normal shock index upon emergency department arrival.

BACKGROUND: The shock index (heart rate divided by systolic blood pressure) of trauma patients upon emergency department arrival predicts blood loss and death. However, some patients with normal shock indices (0.4 < shock index <0.9) upon emergency department arrival also have poor prognoses. This study aimed to determine whether abnormal prehospital shock indices in trauma patients with normal shock indices upon emergency department arrival were predictors of a high risk of mortality. METHODS: We conducted a retrospective cohort study of emergency department-admitted trauma patients from 2004 to 2017. The study included 89,495 consecutive trauma patients aged ≥16 years, with Abbreviated Injury Scale score of ≥3, who were transported to the emergency department directly from the field and had a normal shock index upon emergency department arrival. According to the prehospital shock index scores, the patients were categorized into low shock index (≤ 0.4), normal shock index, and high shock index (≥0.9) groups. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The 89,495 patients had a median age of 64 (interquartile range: 43-79) years, and 55,484 (62.0%) of the patients were male. There were 1350 (1.5%) 24-h deaths in total; 176/4263 (4.1%), 1017/78,901 (1.3%), and 157/6331 (2.5%) patients were in the low, normal, and high prehospital shock index groups, respectively. The adjusted odds ratios for 24-h mortality compared with the normal shock index group were 1.63 (95% confidence interval: 1.34-1.99) in the low shock index group and 1.62 (95% confidence interval: 1.31-1.99) in the high shock index group. CONCLUSION: Trauma patients with abnormal prehospital shock indices but normal shock indices upon emergency department arrival are at a higher risk of 24-h mortality. Identifying these indices could improve triage and targeted care for patients.

Marked hyperkalemia due to inappropriate blood sample storage in two suspected cases of familial pseudohyperkalemia.

We herein report two suspected cases of pseudohyperkalemia who presented with severe hyperkalemia examined at small primary care clinics; however, re-exams at a tertiary care hospital showed normal potassium levels. We reproduced the laboratory examination conditions of the clinics and found that hyperkalemia was due to sampling/storage condition of serum, which is strongly suggestive of familial pseudohyperkalemia (FP). FP is a possible but under-appreciated cause of hyperkalemia, which does not require treatment, so it is important to include FP in the differential diagnosis of hyperkalemia especially in cases with discrepant of serum potassium levels at different settings.

Initiation of renin-angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study.

BACKGROUND: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. METHODS: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR. RESULTS: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively. CONCLUSION: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy.

A case of pericarditis in a middle-aged woman with COVID-19.

The frequency of pericarditis as a complication in COVID-19 patients without underlying disease is not well known. We report a case of COVID-19 presenting with pericarditis without myocarditis or severe respiratory symptoms in a middle-aged woman, who had neither underlying disease nor previous diagnosis of COVID-19.

Culturally Adapted Consensus Definition and Action Guideline: Japan's Advance Care Planning.

CONTEXT: A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making. OBJECTIVES: A consensus definition of advance care planning with action guideline adapted to Japanese society. METHODS: We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan. RESULTS: The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future. CONCLUSION: Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

Doppler trans-thoracic echocardiography for detection of pulmonary hypertension in adults.

BACKGROUND: Pulmonary hypertension (PH) is an important cause of morbidity and mortality, which leads to a substantial loss of exercise capacity. PH ultimately leads to right ventricular overload and subsequent heart failure and early death. Although early detection and treatment of PH are recommended, due to the limited responsiveness to therapy at late disease stages, many patients are diagnosed at a later stage of the disease because symptoms and signs of PH are nonspecific at earlier stages. While direct pressure measurement with right-heart catheterisation is the clinical reference standard for PH, it is not routinely used due to its invasiveness and complications. Trans-thoracic Doppler echocardiography is less invasive, less expensive, and widely available compared to right-heart catheterisation; it is therefore recommended that echocardiography be used as an initial diagnosis method in guidelines. However, several studies have questioned the accuracy of noninvasively measured pulmonary artery pressure. There is substantial uncertainty about the diagnostic accuracy of echocardiography for the diagnosis of PH. OBJECTIVES: To determine the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH. SEARCH METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform from database inception to August 2021, reference lists of articles, and contacted study authors. We applied no restrictions on language or type of publication. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH, where right-heart catheterisation was the reference standard. We excluded diagnostic case-control studies (two-gate design), studies where right-heart catheterisation was not the reference standard, and those in which the reference standard threshold differed from 25 mmHg. We also excluded studies that did not provide sufficient diagnostic test accuracy data (true-positive [TP], false-positive [FP], true-negative [TN], and false-negative [FN] values, based on the reference standard). We included studies that provided data from which we could extract TP, FP, TN, and FN values, based on the reference standard. Two authors independently screened and assessed the eligibility based on the titles and abstracts of records identified by the search. After the title and abstract screening, the full-text reports of all potentially eligible studies were obtained, and two authors independently assessed the eligibility of the full-text reports. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted the authors of the included studies to obtain missing data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity regarding types of PH, methods to estimate the right atrial pressure, and threshold of index test to diagnose PH. All analyses were performed using the Review Manager 5, SAS and STATA statistical software. MAIN RESULTS: We included 17 studies (comprising 3656 adult patients) assessing the diagnostic accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH. The included studies were heterogeneous in terms of patient distribution of age, sex, WHO classification, setting, country, positivity threshold, and year of publication. The prevalence of PH reported in the included studies varied widely (from 6% to 88%). The threshold of index test for PH diagnosis varied widely (from 30 mmHg to 47 mmHg) and was not always prespecified. No study was assigned low risk of bias or low concern in each QUADAS-2 domain assessed. Poor reporting, especially in the index test and reference standard domains, hampered conclusive judgement about the risk of bias. There was little consistency in the thresholds used in the included studies; therefore, common thresholds contained very sparse data, which prevented us from calculating summary points of accuracy estimates. With a fixed specificity of 86% (the median specificity), the estimated sensitivity derived from the median value of specificity using HSROC model was 87% (95% confidence interval [CI]: 78% to 96%). Using a prevalence of PH of 68%, which was the median among the included studies conducted mainly in tertiary hospitals, diagnosing a cohort of 1000 adult patients under suspicion of PH would result in 88 patients being undiagnosed with PH (false negatives) and 275 patients would avoid unnecessary referral for a right-heart catheterisation (true negatives). In addition, 592 of 1000 patients would receive an appropriate and timely referral for a right-heart catheterisation (true positives), while 45 patients would be wrongly considered to have PH (false positives). Conversely, when we assumed low prevalence of PH (10%), as in the case of preoperative examinations for liver transplantation, the number of false negatives and false positives would be 13 and 126, respectively. AUTHORS' CONCLUSIONS: Our evidence assessment of echocardiography for the diagnosis of PH in adult patients revealed several limitations. We were unable to determine the average sensitivity and specificity at any particular index test threshold and to explain the observed variability in results. The high heterogeneity of the collected data and the poor methodological quality would constrain the implementation of this result into clinical practice. Further studies relative to the accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH in adults, that apply a rigorous methodology for conducting diagnostic test accuracy studies, are needed.

Resting respiration rate predicts all-cause mortality in older outpatients.

BACKGROUND: Although respiratory rate has been a sensitive predictor for prognosis in acute settings, resting respiratory rate (RRR) is undervalued in chronic care. The clinical significance of RRR among older people is not well documented. AIM: We investigated the association between RRR and all-cause mortality among older outpatients. METHODS: A retrospective cohort study exhaustively included patients who had undergone medical checkups in a facility between April 2017 and March 2018 and followed up for at least 2 years. We excluded patients who were less than 60 years of age or had not undergone regular outpatient appointments. Sex, age, smoking habits, history of hospitalization, polypharmacy, long-term care insurance certification status, Mazzaglia index, pulse rate, systolic blood pressure, and Charlson Comorbidity Index were measured at the baseline medical checkup. Survival was confirmed by chart review and by contacting physicians in charge. The risk ratios were estimated by converting the odds ratios derived from the multivariable logistic regression models. RESULTS: Of the 853 patients who underwent baseline checkups, 749 were enrolled in the analyses; death occurred in 53 patients (7.1%), with no loss to follow-up. The RRR was independently associated with all-cause mortality after adjusting for covariates [adjusted risk ratio of RRR per 1 bpm = 1.14, 95% confidence interval (CI): 1.06 - 1.22]. DISCUSSION: Given the independent association of RRR for existing predictors, this simple index seems worthy of consideration in further studies aimed at defining its predictive role in older people and in different settings. CONCLUSION: RRR was independently associated with all-cause mortality.