Association of Novel Antihyperglycemic Drugs Versus Metformin With a Decrease in Asthma Exacerbations.

BACKGROUND: Similar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism. OBJECTIVE: To investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes. METHODS: Using a Japanese national administrative database, we constructed 3 active comparators-new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids. RESULTS: DPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs 17.4 per 100 person-years, hazard ratio: 1.09, 95% confidence interval [CI]: 1.05-1.14; GLP-1 RAs: 24.9 vs 19.0 per 100 person-years, hazard ratio: 1.14, 95% CI: 1.01-1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs 18.1 per 100 person-years, hazard ratio: 1.00, 95% CI: 0.97-1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs 56.6 per 100 person-years, rate ratio: 0.95, 95% CI: 0.91-0.99). CONCLUSIONS: While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

Effectiveness of antibiotic therapy for early recurrence of peritonsillar cellulitis and abscesses: A retrospective cohort study.

OBJECTIVE: Short-term recurrence is common in patients with peritonsillar cellulitis and abscesses, leading to socioeconomic problems. Early switching from intravenous to oral antibiotics is feasible for treating certain diseases. However, reports on early switching and total antibiotic administration duration in peritonsillar cellulitis and abscesses are limited. This study aimed to determine the appropriate antibiotic therapy duration and examine the impact of early oral switch therapy on peritonsillar cellulitis and abscesses. METHODS: We retrospectively identified 98,394 patients who received antibiotic therapy during hospitalization for peritonsillar cellulitis and abscesses between July 1, 2010, and December 31, 2019, using the Japanese Diagnosis Procedure Combination database. RESULTS: Propensity score matching analysis revealed no significant between-group difference in the rehospitalization rate (early oral switch therapy and long intravenous therapy: 1.7 % [198 of 11,621] vs. 2.0 % [234 of 11,621], odds ratio [OR] 0.84, 95 % confidence interval [CI] 0.70-1.02). A long total duration of antibiotic therapy (reference: 1-9 days) was associated with a low risk of rehospitalization (10-14 days: OR 0.86, 95 % CI 0.78-0.95; 15+ days: OR 0.51, 95 % CI 0.38-0.66). CONCLUSION: Early oral switch therapy may be a viable option for treating patients with peritonsillar cellulitis and abscesses in good condition who can tolerate oral intake. No less than 10 days of antibiotic therapy is desirable.

Otologic disease trends in Japan post-COVID-19 outbreak: A retrospective time-series analysis.

OBJECTIVE: To evaluate the potential impact of coronavirus disease 2019 (COVID-19) and vaccinations on otologic diseases, including facial nerve paralysis (including Ramsay Hunt syndrome), vestibular neuritis, sudden sensorineural hearing loss, and Meniere's disease. METHODS: In this retrospective study, we conducted a time-series analysis employing a causal impact algorithm on a large-scale inpatient database in Japan. We compared the actual number of hospitalized patients with otologic diseases to two predictions: one without any covariates and another with a covariate accounting for the reduction in the number of hospitalized patients due to lockdown measures. Additionally, we performed Granger causality tests to ensure the robustness of our findings. RESULTS: No significant increase was noted in the number of hospitalized patients with otologic diseases following the onset of the COVID-19 pandemic in the causal impact analysis. Similarly, no notable surge was observed in hospitalizations for these diseases following the introduction of the COVID-19 vaccine. The Granger causality tests results aligned with the causal impact analysis findings. CONCLUSION: Our findings indicate that COVID-19 and vaccinations had minimal discernible effects on hospitalization of patients with otologic diseases, suggesting that otologic diseases may not be significantly impacted by COVID-19 and vaccinations, which could have implications for public health policies and the allocation of healthcare resources during a pandemic. Further research and monitoring of long-term effects are warranted to validate these findings and guide healthcare decision-making.

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

BACKGROUND: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. OBJECTIVE: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. METHODS: A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. RESULTS: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/µL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/µL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. CONCLUSION: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Patient characteristics and procedural and safety outcomes of percutaneous transesophageal gastro-tubing: A nationwide database study in Japan.

BACKGROUND: Percutaneous transesophageal gastro-tubing (PTEG) is an alternative interventional procedure in cases where gastrostomy is not feasible. However, the safety and complication rates of PTEG have not yet been evaluated. We aimed to describe the characteristics of patients who underwent PTEG and investigate complications using a nationwide Japanese inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database in Japan to identify patients who underwent PTEG from April 2012 to March 2020. The outcomes were the occurrence of complications, invasive treatment within 7 days after PTEG, and tube replacement within 14 days after PTEG. We statistically compared patient background, complication rates, and outcomes using PTEG indications. RESULTS: A total of 3,684 patients underwent PTEG, which was performed in 1,455 patients for decompression and 2,193 patients for feeding. The patients' mean age was 73.1 years, and 62.1% were men. More patients in the decompression group had cancer than those in the feeding group. The overall number of complications was 47 cases (1.3%). The most common treatment administered after PTEG was red blood cell transfusion (3.9%), followed by early tube replacement (3.3%). As invasive treatments for PTEG complications, percutaneous drainage and transcatheter arterial embolization were required in 4 and 1 cases, respectively, and no cases required surgery. CONCLUSION: We performed a descriptive study on PTEG using a nationwide database in Japan. This study also showed a low complication rate after PTEG in the real world. Our findings provide practical information on the safety of PTEG in Japan.

Association between volume of patients undergoing stroke rehabilitation at acute care hospitals and improvement in activities of daily living.

BACKGROUND: This study aimed to determine the relationship between the annual volume of patients undergoing rehabilitation per hospital and the outcomes of patients admitted for acute stroke. METHODS: This observational study used nationwide administrative data. Data on stroke patients aged ≥ 20 years who underwent rehabilitation were extracted from 1,182 acute care hospitals in Japan. The exclusion criteria were extended hospital stay exceeding 180 days and death during hospitalization. Hospital volumes were divided into four quartiles of total patients per hospital. The primary outcome was an improvement in activities of daily living from admission to discharge measured using the Barthel index. Poisson regression analysis of activities of daily living improvement was performed using inverse probability of treatment weighting. RESULTS: High rehabilitation volume was significantly correlated with improvements in activities of daily living using the "very low group" as a reference (risk ratio [95% confidence interval]): 1.06 [1.05-1.08], P<0.001). Low volume was also significantly associated with activities of daily living improvement (risk ratio [95% confidence interval]: 1.04 [1.03-1.06], P<0.001). CONCLUSIONS: The annual volume of stroke patients undergoing multidisciplinary rehabilitation at a specific hospital may be a factor in the degree of patient improvement in activities of daily living.

Association Between Systemic Corticosteroid Use and Mortality in Patients with Epiglottitis.

OBJECTIVES: To clarify whether treatment with systemic corticosteroids at a certain dose was associated with better outcomes in patients with epiglottitis requiring airway management (tracheotomy or airway intubation). METHODS: This was a retrospective cohort study on patients hospitalized for epiglottitis requiring airway management from a nationwide inpatient database (between July 2010 and March 2019). Patients treated with systemic corticosteroids equivalent to methylprednisolone ≥40 mg/d within 2 days of admission and patients who were not treated with corticosteroids within 2 days of admission were compared after inverse probability of treatment weighting using covariate balancing propensity score. The primary outcome was all-cause 30-day in-hospital mortality, and secondary outcomes included all-cause 7-day in-hospital mortality, length of hospital stay, and total medical cost. RESULTS: There were 1986 and 1771 patients in the corticosteroid and control groups, respectively. A total of 72 of 3757 (1.9%) patients died within 30 days of admission, including 17 of 1986 (0.9%) patients in the corticosteroid group and 55 of 1771 (3.1%) in the control group (weighted odds ratio, 0.28 [95% confidence interval, 0.11-0.70]; weighted risk difference, -2.2% [-3.2% to -1.3%]). Treatment with corticosteroids was associated with lower total medical costs (weighted median, $6,187 vs. $6,587; weighted difference, $-1,123 [-2,238 to -8]) but not all-cause 7-day in-hospital mortality (weighted odds ratio, 0.63 [0.22-1.82]; weighted risk difference, -0.3% [-0.9 to 0.2]) and length of hospital stay (weighted median, 13 vs. 13 days; weighted difference, -0.2 days [-2.1 to 1.8]). CONCLUSIONS: Systemic corticosteroids may be beneficial to patients with epiglottitis requiring airway management. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:344-349, 2023.

Implementation of Rehabilitation and Patient Outcomes During the Initial COVID-19 Pandemic.

Objectives: This study investigated the impact of the initial outbreak of coronavirus disease (COVID-19) on rehabilitation and functional outcomes of patients in Japanese hospitals. Methods: The study subjects were hospitals belonging to Japan's National Hospital Organization that provided inpatient care for patients with coronavirus COVID-19 during March-May 2020. We specifically focused on patients who were hospitalized for acute diseases, such as stroke, hip fracture, acute myocardial infarction, congestive heart failure, or chronic obstructive pulmonary disease, and received rehabilitation during hospitalization. Data were sourced from Japanese administrative data. The primary outcome was rehabilitation provision time in the target hospitals. The secondary outcomes were patient outcomes: rehabilitation participation time, length of hospital stay, 30-day readmission rate, and improvement of activities of daily living. Interrupted time series analysis was performed to evaluate the trend of rehabilitation provision time. Patient outcomes were compared with those for 2019. Results: The rehabilitation provision time for outpatients declined by 62% during the pandemic, while that for inpatients declined temporarily, and then increased. Compared with 2019 outcomes, rehabilitation participation time was longer and hospital stay length was shorter for stroke and hip-fracture patients, the 30-day readmission rate was increased for hip-fracture patients, and improvement of activities in daily living was less for patients with congestive heart failure who were totally dependent at admission. Other outcomes did not change. Conclusions: The findings suggest that during the initial COVID-19 pandemic, resources for rehabilitation were quickly reallocated to inpatient care, and the impact on inpatient outcomes was minimized.

Economic and clinical burden from carbapenem-resistant bacterial infections and factors contributing: a retrospective study using electronic medical records in Japan.

BACKGROUND: Antimicrobial resistance is a major threat to global health and the world economy. The economic burden of carbapenem-resistant infections has not previously been evaluated. We aimed to compare the potential economic burden and clinical outcomes between carbapenem-resistant infections and carbapenem-susceptible infections in Japan. METHODS: We conducted a retrospective cohort study using electronic medical records. Patients aged 15 years or older and with the diagnosis of pneumonia, urinary tract infection, biliary infection, and sepsis were included. Multivariable regression models with random effects were used to estimate the impact of carbapenem resistance on cost, length of hospital stay, and in-hospital mortality. RESULTS: Among the 9,517 patients, 86 (0.9%) had carbapenem-resistant (CR) infections. Compared to carbapenem-susceptible (CS) infections, the patients with the CR infections were significantly more likely to receive mechanical ventilation (37.2 vs. 21.2%, P-value = 0.003), antibiotics (88.4 vs. 63.0%, P-value < 0.001), and especially carbapenem (31.4 vs. 8.3%, P-value < 0.001), before the bacterial culture test positive. Significantly higher median costs were found for the CR infections than the CS infections in the categories of medications (3477 US dollars vs. 1609 US dollars), laboratory tests (2498 US dollars, vs. 1845 US dollars), and hospital stay (14,307 US dollars vs. 10,560 US dollars). In the multivariable regression analysis, the length of stay was 42.1% longer and the cost was 50.4% higher in the CR infections than in the CS infections. The risk of in-hospital mortality did not differ between the two groups (odds ratio 1.24, 95% CI 0.72-2.11), due to the small sample size. The result was robust with a similar trend in the analysis using the inverse probability treatment weighting method. CONCLUSIONS: Compared to carbapenem-susceptible infections, carbapenem-resistant infections were associated with a higher cost and a longer length of stay. Detailed cost analysis showed significant differences in the categories of medication, laboratory tests, and hospital stay. To our knowledge, this study is the first to assess the potential economic burden of carbapenem-resistant infections using a large hospital-based database.

Existing Data Sources for Clinical Epidemiology: Database of the National Hospital Organization in Japan.

This review introduces the National Hospital Organization (NHO) database in Japan. The NHO has maintained two databases through a system of data collection from 140 hospitals in the NHO. National Hospital Organization Clinical Data Archives (NCDA) is collecting clinical information in real time from the electronic medical records since January 2016, and Medical Information Analysis (MIA) databank is collecting daily insurance claims data since April 2010. The NHO database covers more than 8 million patients in 140 hospitals throughout Japan. The database consists of the information of patient profiles, hospital admission and discharge, diagnosis with ICD-10 codes, text data from medical chart, daily health insurance claims such as medical procedures, medications or surgeries, vital signs and laboratory data, and so on. The NHO database includes a wide variety of diseases and settings, including acute, chronic and intractable diseases, emergency medical services, disaster medicine, response to emerging infectious disease outbreaks, medical care according to health policies such as psychiatry, tuberculosis, or muscular dystrophy, and health systems in sparsely populated non-urban areas. Among several common diseases, the database has representativeness in terms of age distribution compared with the Patient Survey 2017 by the Ministry of Health, Labour and Welfare. Interested researchers can contact (700-dbproject@mail.hosp.go.jp) the NHO database division to obtain more information about the NHO database for utilization.

Real-world benefits of biologics for asthma: Exacerbation events and systemic corticosteroid use.

BACKGROUND: Studies have shown the efficacy of asthma biologics in real-world settings, confirming the generalizability of randomized controlled trial (RCT) results, but studies on more than one biologic are scarce. Accordingly, little is known about the different background characteristics in users of asthma biologics. This study aimed to describe the backgrounds of asthma patients using biologics (omalizumab, mepolizumab, benralizumab, and dupilumab) and examine the effectiveness of these biologics for reducing asthma exacerbations and total systemic corticosteroid doses. METHODS: We conducted a retrospective cohort study using self-controlled methods to evaluate the association between the use of biologics and reduction in exacerbations and hospitalizations using a large-scale health insurance claims database in Japan. RESULTS: Of 355 continuously treated asthma patients using biologics, 119, 82, 69, and 85 patients were assigned to the omalizumab, mepolizumab, benralizumab, and dupilumab groups, respectively. The baseline characteristics differed among users of biologics. The incidence ratios of exacerbations and hospitalizations during biologics use were 0.68 (95% confidence interval, 0.62-0.74) and 0.65 (0.55-0.77) compared with the period before biologics use. The total systemic corticosteroid dose equivalent to prednisolone per person-year was reduced from a median of 600 [interquartile range, 90-1713] mg to 164 [0-1010] mg (P < .001). Similar results were obtained for individual biologics with a few exceptions. CONCLUSIONS: The background characteristics of biologics users differed in a real-world setting. Our results confirmed findings from RCTs demonstrating that each biologic (omalizumab, mepolizumab, benralizumab, and dupilumab) is associated with decreased exacerbation numbers and corticosteroid-sparing effects, even outside of the controlled settings of RCTs.

Consultation-liaison psychiatry in Japan: a nationwide retrospective observational study.

BACKGROUND: Consultation-liaison psychiatry (CLP)-professional psychiatric care provided to coordinate with surgical or medical treatment of inpatients with psychiatric disorders-was included in universal health coverage in Japan in 2012. Despite evidence of benefits of CLP, basic data and geographic distribution information regarding CLP at the national level remain unclear. This study aimed to 1) identify the geographic disparity of CLP in Japan and 2) investigate the association between number of consultations per CLP patient and region. METHODS: We retrospectively analyzed anonymized data retrieved from the Japanese administrative inpatient database regarding inpatients who were provided CLP between April 2012 and March 2017. Demographic characteristics were summarized and geographic disparity by prefecture was visualized for fiscal years 2012 and 2016; we also summarized the data according to region. Multivariate linear regression analysis was used to investigate association between the number of consultations per CLP patient and region after adjusting for covariates. RESULTS: Data from a total of 46,171 patients who received 138,866 CLP services were included. Results revealed more patients aged 75-84 years received CLPs than any other age group (29.7%) and the overall male/female ratio was 53:47 in 2016. In 2012 and 2016, 24.2 and 30.7% of CLP patients, respectively, were transferred to other hospitals; 9.7 and 8.8%, respectively, discharged due to the death. CLP services were provided in 14 prefectures in 2012 and 33 by 2016; 14 prefectures had no available CLP services. After adjusting for covariates, Tohoku (ß = - 0.220, p < 0.034), Chugoku (ß = - 0.160, p < 0.026), and Shikoku (ß = - 0.555, p < 0.001) had a significant negative correlation with the number of consultations per CLP patient compared with Hokkaido region (an adjusted R square (R2) = 0.274). CONCLUSIONS: Our study clarified the characteristics of patients in Japan who received CLPs and the geographic disparity in CLP services. Although 5 years had passed since CLP was introduced, the results imply wide availability of CLP nationally. The analysis data provided may inform future policies to improve CLP services.

Effect of Early Central Venous Catheterization on Mortality Among Patients with Severe Sepsis: A Nationwide Inpatient Database Study.

BACKGROUND: Clinical guidelines for the management of sepsis have accelerated the utilization of central venous catheterization (CVC). However, risks associated with CVC may be high in the initial phase of severe sepsis because of patient instability. The timing of CVC itself has not been fully evaluated. Therefore, we aimed to assess the association between CVC in the initial care of patients with severe sepsis and corresponding mortality rates. PATIENTS AND METHODS: We conducted a nationwide retrospective analysis using the Japanese Diagnosis Procedure Combination database from April 1, 2014 to March 31, 2016. We identified patients who received CVC within 30 days from hospital admission. We compared the 30-day mortality between two groups: patients who received CVC within 2 days (early) after admission and those who received CVC 3 or more days (delayed) after admission, using marginal structural models with inverse probability treatment weighting. RESULTS: We identified 6,028 eligible patients from 911 hospitals among 27,497 patients with severe sepsis for this study; 4,544 (75.4%) received early CVC. Patients with early CVC had poor prognostic baselines and received more intense treatment than patients with delayed CVC. After adjusting for baseline and time-dependent treatment variables, we found that there were no significant differences between patients who received CVC within 2 days after admission and those who received CVC 3 or more days after admission (hazard ratio 0.83, 95% confidence interval 0.62-1.10). CONCLUSIONS: Among patients with severe sepsis, early CVC was not associated with improved in-hospital mortality rates.

Validity of administrative database detection of previously resolved hepatitis B virus in Japan.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person-years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%-89.3%). This study evaluated the PPV of the algorithm of HBV-DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person-years.

Predictors Associated with Survival Among Elderly In-Patients Who Receive Cardiopulmonary Resuscitation in Japan: An Observational Cohort Study.

BACKGROUND: Little is known about the outcomes of in-hospital cardiopulmonary resuscitation (CPR) in Asian populations including elderly patients in Japan. OBJECTIVE: To determine the survival outcome of in-hospital CPR among elderly patients in Japan, and to identify predictors associated with survival. DESIGN: Retrospective cohort study in 81 Japanese hospitals from April 1, 2010 to March 31, 2016. PATIENTS: We included elderly patients (age ≥ 65 years) who received CPR after 2 days of hospitalization. MAIN MEASURES: The primary outcome was survival at hospital discharge and the secondary outcomes were the discharge disposition and consciousness level of patients who survived to hospital discharge. To determine predictors associated with survival after in-hospital CPR, we fit multivariable models for patient-level and institutional-level factors. KEY RESULTS: Among the 5365 patients who received CPR, 595 (11%) survived to discharge. Of those who survived to discharge, 46% of patients were discharged home, and 10% of patients were comatose at discharge. Older age and higher burden of comorbidities were associated with reduced survival. The adjusted OR was 0.35 (95% CI, 0.22-0.55) for age ≥ 90 years compared to age 65-69 years, and 0.68 (95% CI, 0.48-0.97) for Charlson Comorbidity Index score of ≥ 4 compared with score of 0. Other predictors of reduced survival included receiving CPR on weekends compared to weekdays (AOR, 0.63; 95% CI, 0.51-0.77) and in small hospitals compared to large hospitals (AOR, 0.58; 95% CI, 0.40-0.83). CONCLUSIONS: Among elderly patients in Japan, the survival rate of in-hospital CPR was approximately one in ten, and less than half of these patients were discharged home. In addition to older age and higher illness burden, receiving CPR on weekends and/or in small hospitals were significant predictors of reduced survival. These findings should be considered in advanced care planning discussions with elderly patients to avoid subjecting patients to CPR that are likely futile.

Adjunctive Corticosteroids decreased the risk of mortality of non-HIV Pneumocystis Pneumonia.

OBJECTIVES: A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%. But the effectiveness of adjunctive corticosteroids with trimethoprim-sulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP. METHODS: We did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights. RESULT: 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO2] ≤60mm Hg) and 562 were moderate (PaO2 >60mm Hg) at hospital admission. Among patients with severe respiratory status, the adjunctive corticosteroids was associated with lower risk of 60-day mortality (HR 0.71; 95% confidence interval [CI], 0.55-0.91), and significantly decreased mortality rates (24.7% vs 36.6%, P=0.006). In contrast, no significant differences were observed in the risk of 60-day mortality (HR 1.17; 95% CI, 0.73-1.86) and the mortality rate (10.9% vs 9.1%, P=0.516) among patients with moderate respiratory status. CONCLUSION: The adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.

Feedforward regulation of mRNA stability by prolonged extracellular signal-regulated kinase activity.

Extracellular signal-regulated kinase (ERK) plays a central role in signal transduction networks and cell fate decisions. Sustained ERK activation induces cell differentiation, whereas transient ERK results in the proliferation of several types of cells. Sustained ERK activity stabilizes the proteins of early-response gene products. However, the effect of ERK activity duration on mRNA stability is unknown. We analyzed the quantitative relationship between the duration of four ERK activity kinetics and the mRNA expression profile in growth factor-treated cells. Time-course transcriptome analysis revealed that the cells with prolonged ERK activity generally showed sustained mRNA expression of late response genes but not early or mid genes. Selected late response genes decayed more rapidly in the presence of a specific ERK inhibitor than a general transcription inhibitor and the decay rate was not related to the number of AU-rich elements. Our results suggest that sustained ERK activity plays an important role in the lifespan of the mRNA encoded by late response genes, in addition to the previously demonstrated role in protein stabilization of early-response genes, including transcription factors regulating the transcription of mid and late genes. This double-positive regulation of ligand-induced genes, also termed feedforward regulation, is critical in cell fate decisions.