A mixed-methods study on the pharmacological management of pain in Australian and Japanese nursing homes.

BACKGROUND: Understanding how analgesics are used in different countries can inform initiatives to improve the pharmacological management of pain in nursing homes. AIMS: To compare patterns of analgesic use among Australian and Japanese nursing home residents; and explore Australian and Japanese healthcare professionals' perspectives on analgesic use. METHODS: Part one involved a cross-sectional comparison among residents from 12 nursing homes in South Australia (N = 550) in 2019 and four nursing homes in Tokyo (N = 333) in 2020. Part two involved three focus groups with Australian and Japanese healthcare professionals (N = 16) in 2023. Qualitative data were deductively content analysed using the World Health Organization six-step Guide to Good Prescribing. RESULTS: Australian and Japanese residents were similar in age (median: 89 vs 87) and sex (female: 73% vs 73%). Overall, 74% of Australian and 11% of Japanese residents used regular oral acetaminophen, non-steroidal anti-inflammatory drugs or opioids. Australian and Japanese healthcare professionals described individualising pain management and the first-line use of acetaminophen. Australian participants described their therapeutic goal was to alleviate pain and reported analgesics were often prescribed on a regular basis. Japanese participants described their therapeutic goal was to minimise impacts of pain on daily activities and reported analgesics were often prescribed for short-term durations, corresponding to episodes of pain. Japanese participants described regulations that limit opioid use for non-cancer pain in nursing homes. CONCLUSION: Analgesic use is more prevalent in Australian than Japanese nursing homes. Differences in therapeutic goals, culture, analgesic regulations and treatment durations may contribute to this apparent difference.

Nutritional therapy for reducing disability and improving activities of daily living in people after stroke.

BACKGROUND: Stroke patients often face disabilities that significantly interfere with their daily lives. Poor nutritional status is a common issue amongst these patients, and malnutrition can severely impact their functional recovery post-stroke. Therefore, nutritional therapy is crucial in managing stroke outcomes. However, its effects on disability, activities of daily living (ADL), and other critical outcomes have not been fully explored. OBJECTIVES: To evaluate the effects of nutritional therapy on reducing disability and improving ADL in patients after stroke. SEARCH METHODS: We searched the trial registers of the Cochrane Stroke Group, CENTRAL, MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), and AMED (from 1985) to 19 February 2024. We also searched trials and research registries (ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform) and reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared nutritional therapy with placebo, usual care, or one type of nutritional therapy in people after stroke. Nutritional therapy was defined as the administration of supplemental nutrients, including energy, protein, amino acids, fatty acids, vitamins, and minerals, through oral, enteral, or parenteral methods. As a comparator, one type of nutritional therapy refers to all forms of nutritional therapies, excluding the specific nutritional therapy defined for use in the intervention group. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to assess the initial search results. Two review authors independently screened references that met the inclusion criteria, extracted data, and assessed the risk of bias and the certainty of the evidence using the GRADE approach. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous data and the odds ratio (OR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary outcomes were disability and ADL. We also assessed gait, nutritional status, all-cause mortality, quality of life, hand and leg muscle strength, cognitive function, physical performance, stroke recurrence, swallowing function, neurological impairment, and the development of complications (adverse events) as secondary outcomes. MAIN RESULTS: We identified 52 eligible RCTs involving 11,926 participants. Thirty-six studies were conducted in the acute phase, 10 in the subacute phase, three in the acute and subacute phases, and three in the chronic phase. Twenty-three studies included patients with ischaemic stroke, three included patients with haemorrhagic stroke, three included patients with subarachnoid haemorrhage (SAH), and 23 included patients with ischaemic or haemorrhagic stroke including SAH. There were 25 types of nutritional supplements used as an intervention. The number of studies that assessed disability and ADL as outcomes were nine and 17, respectively. For the intervention using oral energy and protein supplements, which was a primary intervention in this review, six studies were included. The results for the seven outcomes focused on (disability, ADL, body weight change, all-cause mortality, gait speed, quality of life, and incidence of complications (adverse events)) were as follows: There was no evidence of a difference in reducing disability when 'good status' was defined as an mRS score of 0 to 2 (for 'good status': OR 0.97, 95% CI 0.86 to 1.10; 1 RCT, 4023 participants; low-certainty evidence). Oral energy and protein supplements may improve ADL as indicated by an increase in the FIM motor score, but the evidence is very uncertain (MD 8.74, 95% CI 5.93 to 11.54; 2 RCTs, 165 participants; very low-certainty evidence). Oral energy and protein supplements may increase body weight, but the evidence is very uncertain (MD 0.90, 95% CI 0.23 to 1.58; 3 RCTs, 205 participants; very low-certainty evidence). There was no evidence of a difference in reducing all-cause mortality (OR 0.57, 95% CI 0.14 to 2.28; 2 RCTs, 4065 participants; low-certainty evidence). For gait speed and quality of life, no study was identified. With regard to incidence of complications (adverse events), there was no evidence of a difference in the incidence of infections, including pneumonia, urinary tract infections, and septicaemia (OR 0.68, 95% CI 0.20 to 2.30; 1 RCT, 42 participants; very low-certainty evidence). The intervention was associated with an increased incidence of diarrhoea compared to usual care (OR 4.29, 95% CI 1.98 to 9.28; 1 RCT, 4023 participants; low-certainty evidence) and the occurrence of hyperglycaemia or hypoglycaemia (OR 15.6, 95% CI 4.84 to 50.23; 1 RCT, 4023 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain about the effect of nutritional therapy, including oral energy and protein supplements and other supplements identified in this review, on reducing disability and improving ADL in people after stroke. Various nutritional interventions were assessed for the outcomes in the included studies, and almost all studies had small sample sizes. This led to challenges in conducting meta-analyses and reduced the precision of the evidence. Moreover, most of the studies had issues with the risk of bias, especially in terms of the absence of blinding and unclear information. Regarding adverse events, the intervention with oral energy and protein supplements was associated with a higher number of adverse events, such as diarrhoea, hyperglycaemia, and hypoglycaemia, compared to usual care. However, the quality of the evidence was low. Given the low certainty of most of the evidence in our review, further research is needed. Future research should focus on targeted nutritional interventions to reduce disability and improve ADL based on a theoretical rationale in people after stroke and there is a need for improved methodology and reporting.

Changes in Polypharmacy and Potentially Inappropriate Medications in Homebound Older Adults in Japan, 2015-2019: a Nationwide Study.

BACKGROUND: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. OBJECTIVE: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. DESIGN: A cross-sectional study. PARTICIPANTS: Using data from the national claims database in Japan, this study included older adults aged ≥ 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). MAIN MEASURES: Number of drugs, prevalence of polypharmacy (≥ 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. KEY RESULTS: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and ß-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. CONCLUSIONS: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC.

The Effect of Home Care Support Clinics on Hospital Readmission in Heart Failure Patients in Japan.

BACKGROUND: Heart failure is common and is associated with high rates of hospitalization. Home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in Japan in 2006 and 2012, respectively. OBJECTIVE: This study aimed to examine the effect of post-discharge care by conventional or enhanced HCSCs on readmission, compared with general clinics. DESIGN: Retrospective cohort study using the Japanese nationwide health insurance claims database. PARTICIPANTS: Participants were ≥65 years of age, admitted for heart failure and discharged between July 2014 and August 2015 and received a home visit within a month following the discharge (n=12,393). MAIN MEASURES: The exposure was the type of medical facility that provides post-discharge home healthcare: general clinics, conventional HCSCs, and enhanced HCSCs. The primary outcome was all-cause readmission for 6 months after the first visit; the incidence of emergency house calls was a secondary outcome. We used a competing risk regression using the Fine and Gray method, in which death was regarded as a competing event. KEY RESULTS: At 6 months, readmissions were lower in conventional (38%) or enhanced HCSCs (38%) than general clinics (43%). The adjusted subdistribution hazard ratio (sHR) of readmission was 0.87 (95% CI: 0.78-0.96) for conventional and 0.86 (0.78-0.96) for enhanced HCSCs. Emergency house calls increased with conventional (sHR: 1.77, 95% CI:1.57-2.00) and enhanced HCSCs (sHR: 1.93, 95% CI: 1.71-2.17). CONCLUSIONS: Older Japanese patients with heart failure receiving post-discharge home healthcare by conventional or enhanced HCSCs had lower readmission rates, possibly due to compensation with more emergency house calls. Conventional and enhanced HCSCs may be effective in reducing the risk of rehospitalization. Further studies are necessary to confirm the medical functions performed by HCSCs.

Dispensing by Family Pharmacists as a Potential Factor in Pharmacist-initiated Prescription Change: A Retrospective Observational Study.

BACKGROUND: No studies in Japan have examined whether dispensing by family pharmacists, who are incentivized by reimbursement to provide continuous and exclusive medication management, results in prescription changes. Our primary objective was to identify the variables affecting prescription changes, particularly to investigate dispensing by family pharmacists as a possible factor. METHODS: We identified 333,503 records of pharmacy claims data from patients aged 65 years or older who received medication instructions at outpatient pharmacies at Tsukuba, a medium-sized city near Tokyo, between April 2018 and March 2019. We extracted data on dispensing by family pharmacists, number of medicines, patient sex, patient age, and pharmacy category. A multilevel modified Poisson regression analysis was performed to analyze the correlation between dispensing by family pharmacists and pharmacist-initiated prescription change. RESULTS: Dispensing by family pharmacists was 1.37 times more likely to involve a record of prescription change than dispensing by non-family pharmacists. Older age, female sex, polypharmacy, and small-scale pharmacies were also found to be factors. CONCLUSION: This study indicated that dispensing by family pharmacists was a potential factor for pharmacist-initiated prescription changes that may prevent excessive medication and limit pharmacological interactions. Since the likelihood of inappropriate prescriptions being issued varies from hospital to hospital, subsequent studies should take into account the quality of each institution.

Facility staffing associated with potentially avoidable hospitalizations in nursing home residents in Japan: a retrospective cohort study.

BACKGROUND: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan. METHODS: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations. RESULTS: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations. CONCLUSIONS: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors.

Evaluation of enhanced home care support clinics regarding emergency home visits, hospitalization, and end-of-life care: a retrospective cohort study in a city of Japan.

BACKGROUND: To meet the increasing demand for home healthcare in Japan as the population ages, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012, respectively. This study aimed to evaluate whether enhanced HCSCs fulfilled the expected role in home healthcare. METHODS: We conducted a retrospective cohort study using linked medical and long-term care claims data from a municipality in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and March 2018, and used either conventional or enhanced HCSCs. Patients were followed up for one year after they started regular home visits or until the month following the end of the regular home visits if they ended within one year. The outcome measures were (i) emergency home visits at all hours and on nights and holidays at least once, respectively, (ii) hospitalization at least once, and (iii) end-of-life care, which was evaluated based on the place of death and whether a physician was present at the time of in-home death. Multivariable logistic regression analyses were conducted for the outcomes of emergency home visits and hospitalizations. RESULTS: The analysis included 802 patients, including 405 patients in enhanced HCSCs and 397 patients in conventional HCSCs. Enhanced HCSCs had more emergency home visits at all hours than conventional HCSCs (65.7% vs. 49.1%; adjusted odds ratio 1.70, 95% CI [1.26-2.28]), more emergency home visits on nights and holidays (33.6% vs. 16.7%; 2.20 [1.55-3.13]), and fewer hospitalizations (21.5% vs. 32.2%; 0.55 [0.39-0.76]). During the follow-up period, 229 patients (152 patients in enhanced HCSCs and 77 patients in HCSCs) died. Deaths at home were significantly more common in enhanced HCSCs than in conventional HCSCs (80.9% vs. 64.9%; p < .001), and physician-attended deaths among those who died at home were also significantly more common in enhanced HCSCs (99.2% vs. 78.0%; p < .001). CONCLUSIONS: This study confirms that enhanced HCSCs are more likely to be able to handle emergency home visits and end-of-life care at home, which are important medical functions in home healthcare. Further promotion of enhanced HCSCs would be advantageous.

Symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes.

OBJECTIVE: To investigate symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes (NHs). METHODS: Secondary cross-sectional analyses of two prospective cohort studies involving 12 Australian NHs and four Japanese NHs. Frailty was measured using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Regular medications were classified as symptomatic or preventive based on published lists and expert consensus. Descriptive statistics were used to compare the prevalence and ratio of symptomatic to preventive medications. RESULTS: Overall, 550 Australian residents (87.7 ± 7.3 years; 73.3% females) and 333 Japanese residents (86.5 ± 7.0 years; 73.3% females) were included. Australian residents used a higher mean number of medications than Japanese residents (9.8 ± 4.0 vs 7.7 ± 3.7, p < 0.0001). Australian residents used more preventive than symptomatic medications (5.5 ± 2.5 vs 4.3 ± 2.6, p < 0.0001), while Japanese residents used more symptomatic than preventive medications (4.7 ± 2.6 vs 3.0 ± 2.2, p < 0.0001). In Australia, symptomatic medications were more prevalent with increasing frailty (non-frail 3.4 ± 2.6; frail 4.0 ± 2.6; most-frail 4.8 ± 2.6, p < 0.0001) but less prevalent with age (< 80 years 5.0 ± 2.9; 80-89 years 4.4 ± 2.6; ≥ 90 years 3.9 ± 2.5, p = 0.0042); while preventive medications remained similar across age and frailty groups. In Japan, there was no significant difference in the mean number of symptomatic and preventive medications irrespective of age and frailty. CONCLUSIONS: The ratio of symptomatic to preventive medications was higher with increasing frailty but lower with age in Australia; whereas in Japan, the ratio remained consistent across age and frailty groups. Preventive medications remained prevalent in most-frail residents in both cohorts, albeit at lower levels in Japan.

Association of physical restraint duration and undesirable outcomes amongst inpatients comorbid with dementia and pneumonia in acute care settings.

AIMS AND OBJECTIVES: This study aimed to examine the association between physical restraint duration and undesirable outcomes amongst inpatients comorbid with dementia and pneumonia in acute care hospitals. BACKGROUND: Physical restraints are frequently used in the management of patients, especially amongst patients with dementia. No previous study investigated the potential undesirable effects of physical restraints in patients with dementia. METHODS: This was a cohort study using a nationwide discharge abstract database in Japan. Patients aged ≥65 years with dementia hospitalised for pneumonia or aspiration pneumonia between April 1, 2016 and March 31, 2019 were identified. The exposure was physical restraint. The primary outcome was hospital discharge to the community. Secondary outcomes included hospitalisation costs, functional decline, in-hospital mortality, and institutionalisation for long-term care. RESULTS: A total of 18,255 inpatients with pneumonia and dementia in 307 hospitals were included in this study. Of them, 21.5% and 23.7% had physical restraint during full and partial days of hospital stays, respectively. Discharge to the community incidence rates was lower in the full-restraint vs. the no-restraint group (27 vs. 29 per 1000 person-days; HR, 1.05 [95% CI, 1.01-1.10]) and the partial-restraint vs. the no-restraint group (17 vs. 29 per 1000 person-days; HR, 1.79 [95% CI, 1.71-1.87]). The risks of functional decline were higher in the full-restraint vs. the no-restraint group (27.8% vs. 20.8%; RR, 1.33 [95% CI, 1.22, 1.46]) and the partial-restraint vs. the no-restraint group (29.2% vs. 20.8%; RR, 1.40 [95% CI, 1.29, 1.53]). CONCLUSIONS: The use of physical restraints was associated with a lower incidence rate of discharge to the community and an increased risk of functional decline at discharge. Further research is needed to judge the benefit-risk balance of physical restraints in acute care settings. RELEVANCE TO CLINICAL PRACTICE: Understanding the risk of physical restraints allows medical staff to improve the process of decision making in everyday practice. No Patient or Public Contribution. REPORTING METHODS: The reporting of this article conforms to the STROBE statement.

National trends in the proportion of in-hospital deaths by cause of death among older adults with long-term care: a nationwide observational study in Japan from 2007 to 2017.

BACKGROUND: Japan has promoted end-of-life care at home and in long-term care facilities, and the total proportion of in-hospital deaths has decreased recently. However, the difference in trends of in-hospital deaths by the cause of death remains unclear. We investigated the variation in trends of in-hospital deaths among older adults with long-term care from 2007 to 2017, by cause of death and place of care. METHODS: Using the national long-term care insurance registry, long-term care claims data, and national death records, we identified people aged 65 years or older who died between 2007 and 2017 and used long-term care services in the month before death. Using a joinpoint regression model, we evaluated time trends of the proportion of in-hospital deaths by cause of death (cancer, heart diseases, cerebrovascular diseases, pneumonia, and senility) and place of care (home, long-term care health facility, or long-term care welfare facility). RESULTS: Of the 3,261,839 participants, the mean age was 87.0 ± 8.0 years, and 59.2% were female. Overall, the proportion of in-hospital deaths decreased from 66.2% in 2007 to 55.3% in 2017. By cause of death, the proportion of in-hospital deaths remained the highest for pneumonia (81.6% in 2007 and 77.2% in 2017) and lowest for senility (25.5% in 2007 and 20.0% in 2017) in all types of places of care. The joinpoint regression analysis showed the steepest decline among those who died of senility, especially among long-term care health facility residents. CONCLUSIONS: The findings of this nationwide study suggest that there was a decreasing trend of in-hospital deaths among older adults, although the speed of decline and absolute values varied widely depending on the cause of death and place of care.

Regional variation in long-term care spending in Japan.

BACKGROUND: Health inequalities are widening in Japan, and thus, it is important to understand whether (and to what extent) there is a regional variation in long-term care (LTC) spending across municipalities. This study assesses regional variation in LTC spending and identifies the drivers of such variation. METHODS: We conducted a cross-sectional study using publicly available municipality-level data across Japan in 2019, in which the unit of analysis was municipality. The outcome of interest was per-capita LTC spending, which was estimated by dividing total LTC spending in a municipality by the number of older adults (people aged ≥ 65). To further identify drivers of regional variation in LTC spending, we conducted linear regression of per-capita spending against a series of demand, supply, and structural factors. Shapley decomposition approach was used to highlight the contribution of each independent variable to the goodness of fit of the regression model. RESULTS: In Fiscal 2019, per-capita LTC spending varied from 133.1 to 549.9 thousand yen (max/min ratio 4.1) across the 1460 municipalities analyzed, showing considerable regional variation. The included covariates explained 84.0% of the total variance in LTC spending, and demand-determined variance was remarkably high, which contributed more than 85.7% of the overall R2. Specifically, the highest contributing factor was the proportion of severe care-need level and care level certification rate. CONCLUSIONS: Our results demonstrate that, even after adjusting for different municipalities' age and sex distribution, there is a large variation in LTC spending. Furthermore, our findings highlight that, to reduce the spending gap between municipalities, the issues underlying large variations in LTC spending across municipalities must be identified and addressed.

Dissociation of the AhR/ARNT complex by TGF-ß/Smad signaling represses CYP1A1 gene expression and inhibits benze[a]pyrene-mediated cytotoxicity.

Cytochrome P450 1A1 (CYP1A1) catalyzes the metabolic activation of polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and is transcriptionally regulated by the aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex upon exposure to PAHs. Accordingly, inhibition of CYP1A1 expression reduces production of carcinogens from PAHs. Although transcription of the CYP1A1 gene is known to be repressed by transforming growth factor-ß (TGF-ß), how TGF-ß signaling is involved in the suppression of CYP1A1 gene expression has yet to be clarified. In this study, using mammalian cell lines, along with shRNA-mediated gene silencing, CRISPR/Cas9-based genome editing, and reporter gene and quantitative RT-PCR assays, we found that TGF-ß signaling dissociates the B[a]P-mediated AhR/ARNT heteromeric complex. Among the examined Smads, Smad family member 3 (Smad3) strongly interacted with both AhR and ARNT via its MH2 domain. Moreover, hypoxia-inducible factor 1α (HIF-1α), which is stabilized upon TGF-ß stimulation, also inhibited AhR/ARNT complex formation in the presence of B[a]P. Thus, TGF-ß signaling negatively regulated the transcription of the CYP1A1 gene in at least two different ways. Of note, TGF-ß abrogated DNA damage in B[a]P-exposed cells. We therefore conclude that TGF-ß may protect cells against carcinogenesis because it inhibits CYP1A1-mediated metabolic activation of PAHs as part of its anti-tumorigenic activities.

Epidemiology of Food Choking Deaths in Japan: Time Trends and Regional Variations.

BACKGROUND: With increasing age globally, more people may become vulnerable to food choking. We investigated the nationwide epidemiology of food choking deaths in Japan. METHODS: Using Japanese Vital Statistics death data between 2006 and 2016, we identified food choking deaths based on the 10th revision of the International Statistical Classification of Diseases code W79 (Inhalation and ingestion of food causing obstruction of respiratory tract) as a primary diagnosis. We assessed the demographics of people with food choking deaths; temporal trends of food choking deaths by the year (overall and by age group), the day of year; and prefecture variations. RESULTS: Overall, 52,366 people experienced food choking deaths (median age, 82 years, 53% were male, and 57% occurred at home). The highest numbers occurred January 1-3, and were lowest in June. Despite a stable total number of cases at around 4,000 yearly, from 2006 to 2016 the incidence proportion declined from 16.2 to 12.1 per 100,000 population among people aged 75-84 years. Among people ≥85 years, the incidence proportion peaked at 53.5 in 2008 and decreased to 43.6 in 2016. The number of food choking deaths varied by prefecture. CONCLUSIONS: There are temporal and regional variations of food choking deaths in Japan, possibly due to the consumption of Japanese rice cake (mochi), particularly over the New Year's holiday.

PDZK1-interacting protein 1 (PDZK1IP1) traps Smad4 protein and suppresses transforming growth factor-ß (TGF-ß) signaling.

Transforming growth factor (TGF)-ß signaling in humans is stringently regulated to prevent excessive TGF-ß signaling. In tumors, TGF-ß signaling can both negatively and positively regulate tumorigenesis dependent on tumor type, but the reason for these opposite effects is unclear. TGF-ß signaling is mainly mediated via the Smad-dependent pathway, and herein we found that PDZK1-interacting protein 1 (PDZK1IP1) interacts with Smad4. PDZK1IP1 inhibited both the TGF-ß and the bone morphogenetic protein (BMP) pathways without affecting receptor-regulated Smad (R-Smad) phosphorylation. Rather than targeting R-Smad phosphorylation, PDZK1IP1 could interfere with TGF-ß- and BMP-induced R-Smad/Smad4 complex formation. Of note, PDZK1IP1 retained Smad4 in the cytoplasm of TGF-ß-stimulated cells. To pinpoint PDZK1IP1's functional domain, we created several PDZK1IP1 variants and found that its middle region, from Phe40 to Ala49, plays a key role in its Smad4-regulating activity. PDZK1IP1 knockdown enhanced the expression of the TGF-ß target genes Smad7 and prostate transmembrane protein androgen-induced (TMEPAI) upon TGF-ß stimulation. In contrast, PDZK1IP1 overexpression suppressed TGF-ß-induced reporter activities, cell migration, and cell growth inhibition. In a xenograft tumor model in which TGF-ß was previously shown to elicit tumor-promoting effects, PDZK1IP1 gain of function decreased tumor size and increased survival rates. Taken together, these findings indicate that PDZK1IP1 interacts with Smad4 and thereby suppresses the TGF-ß signaling pathway.

Antipsychotic use and related factors among people with dementia aged 75 years or older in Japan: A comprehensive population-based estimation using medical and long-term care data.

OBJECTIVES: Antipsychotics are used to manage the behavioral and psychological symptoms of dementia (BPSD), despite their association with greater risks for mortality and cerebrovascular events. Previous studies in Japan have estimated the prevalence of antipsychotics among older adults who took antidementia drugs. Using long-term care (LTC) data, we aimed to obtain more accurate estimates of the prevalence of antipsychotics and to determine factors related to their use in older adults with dementia. METHODS: Medical and LTC claims data and LTC certification data between April 2012 and September 2013 were obtained from a middle-sized suburban city. The 1-year prevalence of antipsychotic use was estimated among individuals with probable dementia aged greater than or equal to 75 years who were prescribed antidementia drugs and/or had dementia based on LTC needs certification data. RESULTS: Of 25 919 participants, 4865 had probable dementia and 1506 were prescribed antidementia drugs. The prevalence of antipsychotics among participants with probable dementia was 10.7%, which was lower than that in those who were prescribed antidementia drugs (16.4%). Among participants with probable dementia with LTC certification data available (N = 4419), lower cognitive function (vs mild; adjusted odds ratio 2.16, 95% confidence interval 1.63-2.86), antidementia drug use (2.27, 1.84-2.81), and institutional LTC services use (2.34, 1.85-2.97) were associated with greater odds of antipsychotic use, whereas older age (greater than or equal to 92 years) was associated with lower odds (vs less than 77 years; 0.42, 0.27-0.65). CONCLUSIONS: These findings may be useful for estimating the burden of BPSD and for taking measures to reduce inappropriate antipsychotic prescription.

Geographical Variation in Psychiatric Admissions Among Recipients of Public Assistance.

BACKGROUND: Understanding the area-specific resource use of inpatient psychiatric care is essential for the efficient use of the public assistance system. This study aimed to assess the geographical variation in psychiatric admissions and to identify the prefecture-level determinants of psychiatric admissions among recipients of public assistance in Japan. METHODS: We identified all recipients of public assistance who were hospitalized in a psychiatric ward in May 2014, 2015, or 2016 using the Fact-finding Survey on Medical Assistance. The age- and sex-standardized number of psychiatric admissions was calculated for each of the 47 prefectures, using direct and indirect standardization methods. RESULTS: A total of 46,559 psychiatric inpatients were identified in May 2016. The number of psychiatric admissions per 100,000 population was 36.6. We found a 7.1-fold difference between the prefectures with the highest (Nagasaki) and lowest (Nagano) numbers of admissions. The method of decomposing explained variance in the multiple regression model showed that the number of psychiatric beds per 100,000 population and the number of recipients of public assistance per 1,000 population were the most important determinants of the number of psychiatric admissions (R2 = 28% and R2 = 23%, respectively). The sensitivity analyses, using medical cost as the outcome and data from different survey years and subgroups, showed similar findings. CONCLUSIONS: We identified a large geographical variation in the number and total medical cost of psychiatric admissions among recipients of public assistance. Our findings should encourage policy makers to assess the rationale for this variation and consider strategies for reducing it.

Household Income Relationship With Health Services Utilization and Healthcare Expenditures in People Aged 75 Years or Older in Japan: A Population-Based Study Using Medical and Long-term Care Insurance Claims Data.

BACKGROUND: This study aimed to determine whether there are disparities in healthcare services utilization according to household income among people aged 75 years or older in Japan. METHODS: We used data on medical and long-term care (LTC) insurance claims and on LTC insurance premiums and needs levels for people aged 75 years or older in a suburban city. Data on people receiving public welfare were not available. Participants were categorized according to household income level using LTC insurance premiums data. The associations of low income with physician visit frequency, length of hospital stay (LOS), and medical and LTC expenditures were evaluated and adjusted for 5-year age groups and LTC needs level. RESULTS: The study analyzed 12,852 men and 18,020 women, among which 13.3% and 41.5%, respectively, were categorized as low income. Participants with low income for both genders were more likely to be functionally dependent. In the adjusted analyses, lower income was associated with fewer physician visits (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI], 0.87-0.92 for men and IRR 0.97; 95% CI, 0.95-0.99 for women), longer LOS (IRR 1.98; 95% CI, 1.54-2.56 and IRR 1.42; 95% CI, 1.20-1.67, respectively), and higher total expenditures (exp(ß) 1.09; 95% CI, 1.01-1.18 and exp(ß) 1.09; 95% CI, 1.05-1.14, respectively). CONCLUSIONS: This study suggests that older people with lower income had fewer consultations with physicians but an increased use of inpatient services. The income categorization used in this study may be an appropriate proxy of socioeconomic status.

Establishing a hospital transfusion management system promotes appropriate clinical use of human albumin in Japan: a nationwide retrospective study.

BACKGROUND: Despite international recommendations to establish hospital transfusion management systems to promote appropriate use of blood products, the general efficacy of establishing such systems has not been proven. This study aimed to validate the effect of establishing such systems for promoting the appropriate use of human albumin. METHODS: In this retrospective observational study, we used a Japanese Diagnosis Procedure Combination (DPC) database from fiscal year 2012 to 2016, which included inpatient records from approximately 1200 hospitals for payment processes in the national medical insurance system. From this existing database, containing approximately 8 million inpatient records per year, we selected patients with emergency due to "bleeding," "sepsis," and "burn injury," by using the International Classification of Diseases and Injuries 10th revision (ICD-10) codes, and hospitals that had one or more patients for each disease group in each fiscal year. We conducted multivariable logistic regression analysis to estimate the relationship between human albumin administration and the state of the hospital transfusion management system. We evaluated temporal trends of mortality rate and length of stay as an indicator of care quality. RESULTS: Overall, 139,853 eligible patients admitted to 682 hospitals were selected. The results of the multivariable logistic regression analysis show that patients who were admitted to hospitals with an established hospital transfusion department introducing good practice criteria of blood products were less likely to be administered human albumin compared with those who were admitted to hospitals not introducing it, by approximately 30% for each of the three disease groups; adjusted odds ratios (95% confidential intervals) were 0.70 (0.59-0.83), 0.75 (0.69-0.81), and 0.71 (0.58-0.87) in the "bleeding," "sepsis," and "burn injury" groups, respectively. The temporal trends evaluation shows that there were no increasing trends of mortality rate and average length of stay against decreasing trends of human albumin administration in any disease groups. CONCLUSIONS: Establishing a hospital transfusion department responsible for promoting appropriate clinical use of blood products could reduce human albumin administration for critically ill patients without loss of care quality. These findings provide support for policy makers and hospital managers to consider establishing such systems.

TMED10 Protein Interferes with Transforming Growth Factor (TGF)-ß Signaling by Disrupting TGF-ß Receptor Complex Formation.

The intensity and duration of TGF-ß signaling determine the cellular biological response. How this is negatively regulated is not well understood. Here, we identified a novel negative regulator of TGF-ß signaling, transmembrane p24-trafficking protein 10 (TMED10). TMED10 disrupts the complex formation between TGF-ß type I (also termed ALK5) and type II receptors (TßRII). Misexpression studies revealed that TMED10 attenuated TGF-ß-mediated signaling. A 20-amino acid-long region from Thr91 to Glu110 within the extracellular region of TMED10 was found to be crucial for TMED10 interaction with both ALK5 and TßRII. Synthetic peptides corresponding to this region inhibit both TGF-ß-induced Smad2 phosphorylation and Smad-dependent transcriptional reporter activity. In a xenograft cancer model, where previously TGF-ß was shown to elicit tumor-promoting effects, gain-of-function and loss-of-function studies for TMED10 revealed a decrease and increase in the tumor size, respectively. Thus, we determined herein that TMED10 expression levels are the key determinant for efficiency of TGF-ß receptor complex formation and signaling.

Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

BACKGROUND: Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. METHODS: We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). CONCLUSIONS: The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis.