Background: It remains unclear whether pharmacist-led educational programs in community pharmacies could increase appropriate ophthalmic visits for patients with diabetes. We assessed efficacy of pharmacist-led education on ophthalmology visits for diabetes.

Methods: We conducted a cluster randomized controlled trial at 32 community pharmacies in Japan, targeting individuals with diabetes with no ophthalmic visits over a year. Pharmacists in the intervention group received online training on diabetic retinopathy and educated patients, while the control group received a pamphlet. The primary outcome was ophthalmic visits during the follow-up period. Generalized estimating equations were performed with two adjusted models: age and sex (model 1), and additionally diabetic retinopathy factors (model 2). Key secondary outcomes were changes in behavior for ophthalmic visits and glycated hemoglobin (HbA1c) levels.

Results: Overall, 268 patients were included (133 intervention and 135 control). Participants' mean age was 60.1 years, and HbA1c level was 7.5%. Ophthalmic visits occurred in 18.8% (25/133) of the intervention and 20.7% (28/135) of the control group, yielding no significant difference (model 1, risk difference [RD] -0.03 [-0.14 to 0.08], risk ratio [RR] 0.88 (0.54 to 1.45); model 2, RD -0.07 [-0.21 to 0.08], RR 0.73 [0.41 to 1.30]). There was no significant difference between the two groups in the mean changes from baseline to 6 months in behavior for ophthalmic visits (0.07 [-0.23 to 0.37]) and HbA1c levels (-0.28 [-0.76 to 0.20]).

Conclusions: Pharmacist-led education on diabetic retinopathy did not increase ophthalmology visits or improve diabetes-related outcomes. Effective strategies to encourage ophthalmology visits are required.

Background This study aimed to evaluate the association between metformin use and the risk of cervical cancer in women with diabetes compared to dipeptidyl peptidase-4 inhibitors (DPP-4is), using a new-user active-comparator design.

Methods We analyzed data from the JMDC claims database for new users of metformin or DPP-4i between 2010–2022 who were women. Propensity score overlap-weighting was applied to adjust for differences in age, complications, comorbidities, and other anti-diabetic medications. Kaplan–Meier curves and Cox proportional hazards models were used to compare cervical cancer incidence between the metformin and DPP-4i groups.

Results A total of 31,269 eligible individuals were identified, comprising 11,466 metformin users and 19,803 DPP-4i users. Cervical cancer occurred in 11 women (34.0/100,000 person-years) from the metformin group and 34 (59.0/100,000 person-years) in the DPP-4i group. Metformin use was associated with a lower risk of cervical cancer in our unadjusted Kaplan–Meier analysis (P = 0.058), and multivariable-adjusted Cox model (hazard ratio, 0.49; 95% CI, 0.22–1.09; P = 0.082), although neither difference was statistically significant.

Conclusions Our findings did not show a statistically significant association between metformin use and cervical cancer incidence. However, this study’s limited sample size precluded definitive conclusions.

Secondary analyses of randomized controlled trials (RCTs) offer an efficient way to maximize the value of existing trial data and explore clinical questions beyond the original trial scope. This review outlines methodological considerations and best practices, emphasizing their role in evidence-based medicine. We describe major RCT data sources and summarize steps for accessing individual participant data. Key methods include formulating research questions, understanding trial design, data processing, statistical analysis, and clinical interpretation. Types of secondary analyses are discussed including subgroup analysis, biomarker studies, health economics, methodological research, adverse event analysis, and predictive modeling. Common challenges, such as data applicability, missingness, generalizability, and multiple testing, are summarized. With advances in data sharing, secondary analyses are expected to drive scientific discovery and provide more evidence for diagnosis and treatment patterns as long as rigorous standards and transparency are maintained.

Background: Polypharmacy management represents a public health concern; however, intervention by community pharmacists remains limited. Therefore, we evaluated the effectiveness of community pharmacy-based educational intervention for improving polypharmacy management using interrupted time series analysis (ITSA).

Methods: We conducted the ITSA of an educational intervention implemented from June to September 2021 across pharmacies under Medical System Network Co., Ltd., Japan. We analyzed pharmacy claims data from April 2020 to May 2024, with no missing values. The intervention included lectures and workshops delivered via cascade training. The primary and secondary outcomes were the number of Fee for Medication Adjustment Support 2 (FMAS2) and Fee for Medication Adjustment Support 1 (FMAS1) per 100,000 patients, respectively. FMAS2 is claimed when pharmacists propose reducing medications for patients taking six or more medications from multiple institutions, and FMAS1 is claimed when the proposal leads to actual reduction.

Results: The study included 404 pharmacies with an average of 569,909 patients per month. After intervention, FMAS2 claims immediately increased by 3.82 per 100,000 people (95% confidence interval (CI): 1.23 to 6.41, p = 0.005), with no significant trend change. FMAS1 claims first increased by 1.29 per 100,000 people (95% CI: 0.49 to 2.09, p = 0.002) but decreased thereafter (95% CI: −0.298 to −0.130, p < 0.001).

Conclusions: Educational intervention increased FMAS2 and FMAS1 claims in the short term. However, the clinical impact of this intervention was small, and its long-term effectiveness is limited. Future efforts should focus on developing sustainable programs and follow-up systems.

Background: New drugs for pediatric immune thrombocytopenia have recently been developed; however, the practice patterns of the different treatments remain unclear in Japan. Methods: Using a national inpatient database, we analyzed recent trends in the treatment practice patterns of pediatric patients with immune thrombocytopenia.

Results: From 2010 to 2021, the proportion of corticosteroid use did not change from 35.2 to 33.4%, whereas the proportion of intravenous immunoglobulin increased from 66.0 to 76.2% (P trend 0.003), and rituximab, romiplostim, and eltrombopag increased from 0.2 to 0.7%, 0.0 to 1.4%, and 0.3 to 7.5%, respectively, (P trend <0.001, 0.003, and <0.001, respectively). The proportion of no-treatment decreased from 20.2 to 6.5% (P trend <0.001). None of the patients had undergone splenectomy since 2016. Intravenous immunoglobulin and corticosteroids were mostly used at 1.0 g/kg and 2.0 mg/kg per day, respectively. We compared clinical practice patterns and outcomes between the only one-treatment and no-treatment groups. Intravenous immunoglobulin tended to be used in non-academic hospitals and younger patients; however, more risk of readmissions within 6 months occurred. Second-line treatment tended to be used in academic hospitals and older patients.

Conclusions: We observed an increasing trend in intravenous immunoglobulin use and second-line treatment, no change in corticosteroid use, and a decreasing trend in no-treatment approaches, using a national inpatient database. The hospital type might have affected the practice patterns. Clinicians might have chosen the optimal treatment for pediatric patients with immune thrombocytopenia considering several factors and patient backgrounds.

Introduction: Miller Fisher syndrome (MFS) is typically associated with a benign course and spontaneous recovery. However, immunotherapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PE) are often administered for this condition because of the potential for clinical deterioration. We aimed to evaluate the real-world use of immunotherapies in MFS management using a nationwide Japanese database.

Methods: We conducted a retrospective cohort study between April 2014 and March 2020 using the Japanese Diagnosis Procedure Combination database. Patient demographics and treatment modalities were described. Outcomes included length of hospital stay, in-hospital mortality, hospitalization cost, and activities of daily living defined by the Barthel index score.

Results: We identified 1,595 patients with MFS. Of these, 999 (62.6%) received immunotherapy (including IVIG for 908 [56.9%] patients, intravenous methylprednisolone for 219 [13.7%] patients, and PE for 18 [1.8%] patients). In patients with and without immunotherapy, the median length of hospital stay was 18 and 12 days, in-hospital mortality was 0.7% and 0.2%, median total hospitalization costs were ¥1,660,200 and ¥549,375, and the proportions of Barthel index score of 95–100 at discharge were 75.3% and 75.2%, respectively.

Conclusion: Our findings highlight the widespread use of immunotherapies for MFS in Japan despite its generally favorable natural course.

Background: Extracorporeal membrane oxygenation (ECMO) is a vital intervention in patients with severe cardiogenic shock or respiratory failure who are unresponsive to conventional therapies. Despite advances in ECMO technology and management, complications such as infections, renal dysfunction, and post-intensive care syndrome remain significant challenges that contribute to high mortality. Existing registries have provided valuable insights but lack detailed data on infection management, rehabilitation practices, and other granular aspects of ECMO care. The Japan Intensive Care ECMO Consortium: Nationwide Effort for ECMO Care Optimization and Excellence (ECMO NEXT) study aims to address these gaps by establishing a comprehensive multicenter study in Japan.

Methods: This is a multicenter, retrospective cohort study conducted at 22 healthcare institutions in Japan, with data collected on ECMO cases between January 2018 and December 2023. Adults aged ≥18 years who underwent ECMO in the intensive care unit (ICU) during this period will be eligible. This study will focus on six predefined themes: post-decannulation fever, infection epidemiology, ventilator settings, ECMO-associated acute kidney injury and electrolyte abnormalities, rehabilitation practices, and venoarterial ECMO in toxicological emergencies and septic shock scenarios. Data—including clinical course, laboratory results, rehabilitation details, and outcomes—will be collected using a standardized electronic case report form on the Research Electronic Data Capture platform. Statistical models, including propensity score-based analyses, will be used to adjust for confounders and assess attributable risks.

Conclusions: The ECMO NEXT study provides high-resolution data to address the gaps in ECMO research, particularly in ICU management and post-ECMO recovery.

Background: Postpartum haemorrhage (PPH) is a major cause of maternal mortality worldwide. Previous studies have presented varying conclusions regarding the PPH risk in pregnant haemophilia carriers or women with von Willebrand disease (VWD). We aimed to evaluate PPH occurrence in this demographic using a nationwide inpatient database in Japan.

Methods: In this retrospective study, we identified women aged 15–49 years who gave birth while hospitalised between July 2010 and March 2021, using the Japanese Diagnosis Procedure Combination database. These pregnant women were categorised into three groups: the haemophilia, VWD, and control cohort groups. The assessed outcomes were PPH and interventions for bleeding. Multivariable logistic regression analyses were performed to assess the association between coagulation disorders and patient outcomes.

Results: We identified 113 pregnant women in the haemophilia group, 184 in the VWD group, and 1,459,451 in the control group. The outcomes of multivariable logistic regression analyses demonstrated that PPH occurrence was not higher in the haemophilia group (odds ratio, 0.74; 95% confidence interval, 0.46–1.17) than in the control group. Conversely, the VWD group was significantly associated with PPH (odds ratio, 1.46; 95% confidence interval, 1.05–2.02) and a higher incidence of interventions for bleeding (odds ratio, 2.49; 95% confidence interval, 1.55–4.00).

Conclusions: Despite the absence of a substantial correlation between haemophilia and PPH in pregnant haemophilia carriers, a discernible association emerged between VWD and PPH in pregnant women. Healthcare providers need to be mindful of the high prevalence of undiagnosed VWD and prepare adequately for delivery.

Background

Childhood vaccinations can be effective for preventing not only infectious diseases but also other diseases and traumas. This is because vaccines may have nonspecific immunological effects. Additionally, visits for vaccinations may benefit doctors in promoting the overall health of children. We assessed whether vaccination status at 24 months was associated with the incidence of all-cause hospitalization.

Methods

This retrospective cohort study used the vaccine records and healthcare claims from a Japanese city. We included children born between April 2014 and December 2020. Children who took all the following vaccine doses covered by the national immunization program at 24 months of age were defined as having an age-appropriate vaccination status: four doses of Hemophilus influenza type b, four of 13-valent pneumococcal conjugate, four of diphtheria, tetanus, acellular pertussis, and inactivated polio, three of hepatitis B virus, one of Bacille de Calmette et Guérin, one of measles and rubella, and one of varicella-zoster virus. A Cox regression model compared all-cause hospitalizations between children with and without age-appropriate vaccination, adjusting for sex, birth year, and comorbidities.

Results

We identified 2,492 children: 1,689 were age-appropriate vaccinated, and 803 were not. There was no significant difference in all-cause hospitalizations (adjusted hazard ratio, 0.93; 95% confidence interval, 0.69 to 1.3; P=0.65).

Conclusions

The effect of age-appropriate vaccinations on the overall health of children may be small.

Background: Routinely collected medical data, such as electronic medical records (EMRs) and medical claims, are necessary for developing disease registries. This study aimed to develop an otologic surgery registry by integrating data from EMRs, medical claims, and otorhinolaryngology department information systems (ORL-DIS) and to assess the agreement of hearing tests between registry-determined evaluations (RDE) and surgeon-determined evaluations (SDE).

Methods: A stapes surgery registry was developed by linking data from ORL-DIS, EMRs, and medical claims from two hospitals in Japan. SDE were recorded by the surgeons, whereas RDE were automatically assigned by the registry system. This study focused on pre- and postoperative hearing evaluations. Pure-tone averages (PTA) for air conduction (AC) and bone conduction (BC) were calculated. Agreement between SDE and RDE was assessed using Bland–Altman plots, and mean differences and 95% limits of agreement (95% LoA) were calculated. In SDE, cases with incomplete data were excluded.

Results: A total of 164 patients (187 cases) were included. The Bland–Altman analysis revealed a high agreement between preoperative AC-PTA (mean difference: −1.61 dB; 95% LoA: −12.5 to 9.29 dB) and BC-PTA (mean difference: −1.05 dB; 95% LoA: −13.9 to 11.8 dB) measurements by SDE and RDE. Additionally, postoperative improvements showed a moderate agreement. The integration of audiometric data into the registry significantly reduced manual errors.

Conclusion: This study successfully established the first otologic surgery registry in Japan that integrates audiometric data from EMRs. This registry provides a valuable resource for analyzing surgical outcomes and a framework for future otologic research.