Objective：We aimed to evaluate the important potential risks listed in the risk management plans of SGLT–2 inhibitors (SGLT–2i) using a real world database.Design: A cohort study of patients prescribed either SGLT–2i (exposure group) or DPP–4 inhibitors (DPP–4i, control group), using a large–scale health insurance database including claims and specific health checkup.Methods：The study population included the patients with type 2 diabetes between April 2014 and August 2021, and received either SGLT–2i or DPP–4i monotherapy, based on the claims in the database provided by DeSC Healthcare, Inc．The comparability between treatment groups was ensured by propensity score matching (PSM) and inverse probability treatment weighting (IPTW). The outcome events included liver disorder, malignant tumors, fractures, cardiovascular disease, acute pancreatitis, acute kidney injury, and lower limb amputation. Hazard ratios (HRs) were estimated using the Cox proportional hazards model, in addition to five types of bias analyses.Results：In the PSM population, the HRs (95% confidential interval [CI]) of the SGLT–2i group versus the DPP–4i group were 0.63 (0.28–1.44) for acute kidney injury, 0.75 (0.58–0.95) for fractures, 0.85 (0.67–1.07) for liver disorders, 0.87 (0.71–1.05) for cardiovascular diseases, 1.15 (0.88–1.51) for malignant tumors, 1.51 (0.71–3.19) for acute pancreatitis, and with no observation of lower limb amputation．In the IPTW population, the HRs (95% CI) of the SGLT–2i group versus the DPP–4i group were 0.72 (0.47–1.10) for acute kidney injury, 0.76 (0.67–0.86) for fractures, 0.91 (0.80–1.02) for liver disorders, 0.86 (0.78–0.94) for cardiovascular diseases, 1.04 (0.92–1.18) for malignant tumors, 1.81 (1.24–2.64) for acute pancreatitis, and 2.89 (0.69–12.1) for lower limb amputation. The ad hoc analysis of malignant tumors by type revealed several organ–specific statistically significant increases or decreases in HRs among the IPTW subjects; however, no significant overall HR for malignant tumors was observed. Some of the bias analysis revealed that there were significant decreases in HRs for acute kidney injury and liver disorders and a significant increase in HR for lower limb amputation.Conclusion：In comparison to DPP–4i, the use of SGLT–2i was not associated with overall risk of malignant tumors. Further confirmatory studies with fit–for–purpose design are warranted to verify the potential, increased or decreased organ–specific risks of malignant tumors by type and the results suggesting decreased risks of bone fracture and cardiovascular diseases, and an increased risk of acute pancreatitis.

There is growing interest in generating evidence from routinely collected real-world data to support medical and regulatory decision-making. However, longitudinal study designs using real-world data are often complex, and text-only descriptions make it difficult for most readers to understand their designs. To address this issue, in 2019, experts from industry, government, and academia developed the “design diagram,” a framework for visualizing longitudinal study designs. The design diagram uses standardized terminology and a graphical structure to communicate study design details to readers, thereby improving reproducibility. Based on previous work by a joint task force between the International Society for Pharmacoepidemiology (ISPE) and the Professional Society for Health Economics and Outcomes Research (ISPOR), the diagram includes a comprehensive set of key study parameters related to reproducibility. It successfully presents study designs in an unambiguous and intuitive manner. Diagrams have been proposed for various study designs, including cohort, nested case-control, and self-controlled designs. Recently, a new diagram was developed that adds at-a-glance elements to show the observability of the source data used in the study. The use of design diagrams is recommended in both the ISPE/ISPOR-endorsed harmonized protocol template (HARPER) and in reporting guidelines for pharmacoepidemiological research, and its widespread use is expected. This paper describes the structure of the design diagram and provides examples of its use. Effective use of design diagrams is expected to improve the reproducibility and reliability of database studies.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data. METHODS: This retrospective cohort study included 149,620 CKD patients aged 40-74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate. RESULTS: During 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT. CONCLUSIONS Among CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.
Aged ; Cohort Studies ; Databases, Factual ; Disease Progression ; Female ; Health Benefit Plans, Employee ; Humans ; Japan/epidemiology* ; Life Style ; Male ; Meals ; Middle Aged ; Proportional Hazards Models ; Renal Insufficiency, Chronic/therapy* ; Renal Replacement Therapy ; Retrospective Studies ; Sleep ; Smoking/epidemiology*

Objective: “Drug Guide for Patients” (DGP) is a drug information tool designated as one of the routine risk minimization activities in risk management plan (RMP) developed by the Ministry of Health, Labour and Welfare. However, patients and their families hardly recognize DGP. Therefore, we administered a questionnaire on drug consultation service of pharmaceutical companies that provide DGP with an aim to collect their views, elucidate problems when they prepare DGPs and examine effective utilization of DGP in the future.Methods: We sent a questionnaire by letter for 127 drug consultation service of pharmaceutical companies, and received questionnaire results using “Questant” that is web questionnaire making software. The results were examined using Fisher’s exact test or Pearson’s chi-squared test.Results: We obtained responses from 84 (66.1%) companies out of 127. As for the question of the published situation of DGP on their website, the most companies responded “Not published” with 47.6% and subsequently 41.7% for “Published for healthcare professionals”. The combined rate of “Published for Patients (3.6%)” and “Published for both healthcare professionals and patients (7.1%)” was only 10.7%. On the other hand, regarding the burden of companies making DGP, we found that more than 60% of pharmaceutical companies (63.5%) felt burdensome, whereas only 36.5% responded “Not burdensome.” Regarding the question on the role of DGP in RMP, pharmaceutical companies answered that the role is “sufficient” 3.6%, 29.8% “not sufficient”, and 66.6% “unknown”.Conclusion: Our results suggested that it is difficult for patients to get DGP from website of pharmaceutical companies and pharmaceutical companies felt burdensome in making DGP, and they recognized that DGP was not very much utilized by patients. Therefore, it would be necessary to improve the creation criteria of DGP. Furthermore, we felt it necessary to have the DGP known and utilized widely by (consumers and) patients.

Objective: Adequate periconceptional intake of folic acid decreases the risk of neural tube defects.  The present study aimed to investigate pharmacists’ awareness of the importance of folic acid intake for the prevention of neural tube defects and to identify factors associated with pharmacists’ awareness.
Design: Questionnaire survey.
Methods: A self-administered questionnaire regarding the importance of folic acid intake for the prevention of neural tube defects was distributed to pharmacists who attended educational seminars offered by the Sendai City Pharmaceutical Association in December 2010.
Results: Among the 166 respondents, 104 (62.7%) pharmacists were aware that folic acid intake decreases neural tube defects.  After stratification for age and sex including history of delivery, female gender and history of delivery were significantly associated with the awareness of the importance of folic acid intake only among pharmacists younger than 40 years old. Of 104 pharmacists who recognized the importance of folic acid intake for the prevention of neural tube defects, 51.0% and 27.9% recognized that women should begin intake of folic acid before conception and should take about 400 μg of folic acid per day during pregnancy, respectively.
Conclusion: Although about 60% of pharmacists recognized that folic acid intake decreases the risk of neural tube defects, many did not know the intake level required to effectively prevent neural tube defects.  Therefore, more aggressive promotion of the awareness of the importance of folic acid intake among pharmacists is warranted.