TNF-α inhibitor use during pregnancy and the risk of preeclampsia: population-based cohort study.

BACKGROUND: Although the clinical importance of preeclampsia is widely recognized, few treatment options are available for prevention. TNF-α inhibitors have been hypothesized to potentially prevent the disease. We aimed to examine whether exposure to TNF-α inhibitors during pregnancy reduces the risk of preeclampsia. METHODS: We conducted a population-based pregnancy cohort study using nationwide samples of publicly (Medicaid data, 2000-2018) and commercially (MarketScan Research Database, 2003-2020) insured pregnant women linked to their liveborn infants. Exposure was ascertained based on a filled prescription or administration code for TNF-α inhibitors during the first and second trimester of pregnancy. The outcomes included early-onset preeclampsia, late-onset preeclampsia, and small-for-gestational age. For baseline confounding adjustment, we leveraged propensity score overlap weights to estimate risk ratios (RR). RESULTS: Among 4 315 658 pregnancies in the Medicaid and the MarketScan cohort, 2736 (0.063%) were exposed to TNF-α inhibitors during the first trimester and 1712 (0.040%) during the second trimester. After adjustment, the risk of early-onset preeclampsia was not decreased among mothers exposed during the first trimester compared with unexposed women with treatment indications [RRpooled: 1.25, 95% confidence interval (CI) 0.93-1.67]. Similarly, the risk of late-onset preeclampsia was not decreased among mothers exposed during the second trimester compared with unexposed women (RRpooled: 0.99, 95% CI 0.81-1.22). CONCLUSION: Contrary to the hypothesis, exposure to TNF-α inhibitors during pregnancy did not appear to be associated with a reduced risk of early-onset or late-onset preeclampsia. These findings do not support consideration of the use of TNF-α inhibitors for the prevention of preeclampsia.

Characteristics and in-hospital mortality of patients with COVID-19 from the first to fifth waves of the pandemic in 2020 and 2021 in the Japanese Medical Data Vision database.

Objectives: We aimed to describe patient characteristics, healthcare utilization, and in-hospital mortality among patients with COVID-19 in Japan across waves. Methods: Using a large-scale hospital-based database, we identified patients hospitalized for COVID-19 in the first (January-June 2020), second (June-October 2020), third (October 2020-February 2021), fourth (March-June 2021), and fifth (June-December 2021) waves. We summarized patient characteristics, healthcare utilization, and in-hospital mortality during each wave and performed multivariable logistic regression analyses for in-hospital mortality. Results: From the first to fifth waves, the number of patients (mean age ± standard deviation, years) was 2958 (61.2 ± 22.8), 7981 (55.6 ± 25.3), 18,788 (63.6 ± 22.9), 17,729 (60.6 ± 22.6), and 23,656 (51.2 ± 22.3), respectively. There were 190 (6.4%), 363 (4.5%), 1261 (6.7%), 1081 (6.1%), and 762 (3.2%) in-hospital deaths, respectively. The adjusted odds ratios for in-hospital deaths (95% confidence interval) were 0.78 (0.65-0.95), 0.94 (0.79-1.12), 0.99 (0.84-1.18), 0.77 (0.65-0.92), in the second to fifth waves, respectively, compared with the first wave. Conclusions: In-hospital COVID-19 mortality improved from the first to the second wave; however, during the third and fourth waves, mortality was as serious as in the first wave. Although in-hospital mortality during the fifth wave improved, careful monitoring is needed for upcoming waves, considering changing patient and viral characteristics.

Pulse Methylprednisolone Versus Dexamethasone in COVID-19: A Multicenter Cohort Study.

Although pulse (high-dose) methylprednisolone therapy can hypothetically control immune system flare-ups effectively, the clinical benefit of pulse methylprednisolone compared with dexamethasone in COVID-19 remains inconclusive. OBJECTIVES: To compare pulse methylprednisolone to dexamethasone as a COVID-19 treatment. DESIGN SETTING AND PARTICIPANTS: Using a Japanese multicenter database, we identified adult patients admitted for COVID-19 and discharged between January 2020 and December 2021 treated with pulse methylprednisolone (250, 500, or 1,000 mg/d) or IV dexamethasone (≥ 6 mg/d) at admission day 0 or 1. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, new ICU admission, insulin initiation, fungal infection, and readmission. Multivariable logistic regression was conducted to differentiate the dose of pulse methylprednisolone (250, 500, or 1,000 mg/d). Additionally, subgroup analyses by characteristics such as the need for invasive mechanical ventilation (IMV) were also conducted. RESULTS: A total of 7,519, 197, 399, and 1,046 patients received dexamethasone, 250, 500, and 1,000 mg/d of methylprednisolone, respectively. The crude in-hospital mortality was 9.3% (702/7,519), 8.6% (17/197), 17.0% (68/399), and 16.2% (169/1,046) for the different doses, respectively. The adjusted odds ratio (95% CI) was 1.26 (0.69-2.29), 1.48 (1.07-2.04), and 1.75 (1.40-2.19) in patients starting 250, 500, and 1,000 mg/d of methylprednisolone, respectively, compared with those starting dexamethasone. In subgroup analyses, the adjusted odds ratio of in-hospital mortality was 0.78 (0.25-2.47), 1.12 (0.55-2.27), and 1.04 (0.68-1.57) in 250, 500, and 1,000 mg/d of methylprednisolone, respectively, among patients with IMV, whereas the adjusted odds ratio was 1.54 (0.77-3.08), 1.62 (1.13-2.34), and 2.14 (1.64-2.80) among patients without IMV. CONCLUSIONS AND RELEVANCE: Higher doses of pulse methylprednisolone (500 or 1,000 mg/d) may be associated with worse COVID-19 outcomes when compared with dexamethasone, especially in patients not on IMV.

Comparative risk of fracture in community-dwelling older adults initiating suvorexant versus Z-drugs: Results from LIFE study.

BACKGROUND: An increased risk of fracture has been reported in older adults taking hypnotics. However, few studies have reported the comparative safety of hypnotics with different mechanisms of action. We examined the risk of fracture in older adults initiating suvorexant compared to those initiating Z-drugs. METHODS: We conducted a retrospective cohort study using a claims database within a longevity improvement and fair evidence (LIFE) study in Japan (1.5 million beneficiaries). People aged ≥65 years were included in this study. Exposure was defined as the initiation of either suvorexant or Z-drugs (eszopiclone, zolpidem, or zopiclone). The evaluated outcomes were hip fracture and all-cause fracture requiring hospitalization. We used inverse probability of treatment weights to adjust for confounding and followed the incidence of the outcome for three different periods: 30, 90, and 365 days. Cox proportional hazards models were fitted to the weighted population to estimate hazard ratios (HRs). Sensitivity analyses were performed with narrowed outcome definitions and inverse probability of censoring weights. RESULTS: We identified 16,148 suvorexant new users and 54,327 Z-drugs new users. During the 30-day follow-up, 21 (16.6 events per 1000 person-years) and 53 hip fractures (12.2 events per 1000 person-years) were identified among suvorexant and Z-drugs new users, respectively (HR: 1.01, 95% confidence interval [CI]: 0.58-1.76). The analysis for all-cause fracture showed an HR of 1.03 (95% CI: 0.78-1.36). Extended follow-up (90 and 365 days) showed similar results for both outcomes. Sensitivity analyses showed consistent results except for an increased risk of all-cause fracture requiring surgery (HR: 1.41, 95% CI: 0.87-2.29) during the 30-day follow-up. CONCLUSIONS: This is the first study to show that suvorexant has a generally comparable risk of fracture as compared to Z-drugs. Further research is needed to investigate the potential short-term increased risk of all-cause fracture requiring surgery among suvorexant initiators.

Association between pre-admission anticoagulation and in-hospital death, venous thromboembolism, and major bleeding among hospitalized COVID-19 patients in Japan.

PURPOSE: The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease-2019 (COVID-19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID-19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre-admission anticoagulation treatment and three outcomes: in-hospital death, VTE, and major bleeding among hospitalized COVID-19 patients in Japan. METHODS: Using a large-scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID-19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre-admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in-hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre-admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes. RESULTS: Among the 2612 analytic patients, 179 (6.9%) had pre-admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in-hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre-admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75-2.08) for in-hospital death, 0.21 (0.02-1.97) for VTE, and 2.63 (0.80-8.65) for major bleeding. Several sensitivity analyses did not change the results. CONCLUSIONS: We found no evidence that pre-admission anticoagulation treatment was associated with in-hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding.

Comparison of patient characteristics and in-hospital mortality between patients with COVID-19 in 2020 and those with influenza in 2017-2020: a multicenter, retrospective cohort study in Japan.

BACKGROUND: COVID-19 has worse mortality than influenza in American and European studies, but evidence from the Western Pacific region is scarce. METHODS: Using a large-scale multicenter inpatient claims data in Japan, we identified individuals hospitalised with COVID-19 in 2020 or influenza in 2017-2020. We compared patient characteristics, supportive care, and in-hospital mortality, with multivariable logistic regression analyses for in-hospital mortality overall, by age group, and among patients with mechanical ventilation. FINDINGS: We identified 16,790 COVID-19 patients and 27,870 influenza patients, with the different age distribution (peak at 70-89 years in COVID-19 vs. bimodal peaks at 0-9 and 80-89 years in influenza). On admission, the use of mechanical ventilation was similar in both groups (1·4% vs. 1·4%) but higher in the COVID-19 group (3·3% vs. 2·5%; p<0·0001) during the entire hospitalisation. The crude in-hospital mortality was 5·1% (856/16,790) for COVID-19 and 2·8% (791/27,870) for influenza. Adjusted for potential confounders, the in-hospital mortality was higher for COVID-19 than for influenza (adjusted odds ratio [aOR] 1·83, 95% confidence interval [CI] 1·64-2·04). In age-stratified analyses, the aOR (95%CI) were 0·78 (0·56-1·08) and 2·05 (1·83-2·30) in patients aged 20-69 years and ≥70 years, respectively (p-for-interaction<0·0001). Among patients with mechanical ventilation, the aOR was 0·79 (0·59-1·05). INTERPRETATION: Patients hospitalised with COVID-19 in Japan were more likely to die than those with influenza. However, this was mainly driven by findings in older people, and there was no difference once mechanical ventilation was started. FUNDING: Ministry of Health, Labour and Welfare of Japan (21AA2007).

Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study.

Nafamostat mesylate may be effective against coronavirus disease 2019 (COVID-19). However, it is not known whether its use is associated with reduced in-hospital mortality in clinical practice. We conducted a retrospective observational study to evaluate the effect of nafamostat mesylate in patients with COVID-19 using the Medical Data Vision Co. Ltd. hospital-based database in Japan. We compared patients with COVID-19 who were (n = 121) and were not (n = 15,738) administered nafamostat mesylate within 2 days of admission between January and December 2020. We conducted a 1:4 propensity score matching with multiple imputations for smoking status and body mass index and combined the 20 imputed propensity score-matched datasets to obtain the adjusted odds ratio for in-hospital mortality. Crude in-hospital mortality was 13.2% (16/121) and 5.0% (790/15,738), respectively. In the propensity score-matched analysis with multiple imputations, the adjusted odds ratio (use vs. no use of nafamostat mesylate) for in-hospital mortality was 1.27 (95% confidence interval: 0.61-2.64; p = 0.52). Sensitivity analyses showed similar results. The results of this retrospective observational study did not support an association between nafamostat mesylate and improved in-hospital outcomes in patients with COVID-19, although further studies with larger sample sizes are warranted to assess the generalizability of our findings.

Factors associated with long-term urinary catheterisation and its impact on urinary tract infection among older people in the community: a population-based observational study in a city in Japan.

OBJECTIVES: This study aimed to identify factors associated with long-term urinary catheterisation (LTUC) in community-dwelling older adults and to evaluate the risk of urinary tract infection (UTI) among people with LTUC. DESIGN: Population-based observational study. SETTING: Medical and long-term care insurance claims data from one municipality in Japan. PARTICIPANTS: People aged ≥75 years living at home who used medical services between October 2012 and September 2013 (n=32 617). OUTCOME MEASURES: (1) Use of LTUC, defined as urinary catheterisation for at least two consecutive months, to identify factors associated with LTUC and (2) the incidence of UTI, defined as a recorded diagnosis of UTI and prescription of antibiotics, in people with and without LTUC. RESULTS: The 1-year prevalence of LTUC was 0.44% (143/32 617). Multivariable logistic regression analysis showed that the male sex, older age, higher comorbidity score, previous history of hospitalisation with in-hospital use of urinary catheters and high long-term care need level were independently associated with LTUC. The incidence rate of UTI was 33.8 and 4.7 per 100 person-years in people with and without LTUC, respectively. According to multivariable Poisson regression analysis, LTUC was independently associated with UTI (adjusted rate ratio 2.58, 95% CI 1.68 to 3.96). Propensity score-matched analysis yielded a similar result (rate ratio 2.41, 95% CI 1.45 to 4.00). CONCLUSIONS: We identified several factors associated with LTUC in the community, and LTUC was independently associated with the incidence of UTI.