Drug use investigation on the safety and efficacy of tigecycline in Japan (all-case post-marketing surveillance).

INTRODUCTION: We conducted a drug use investigation to investigate the safety and efficacy of tigecycline, which has been approved for clinical use for the treatment of multidrug-resistant gram-negative infections in Japan. METHODS: This was an open-label, observational, multicenter cohort study that included all patients who received tigecycline. RESULTS: A total of 116 patients were registered between December 2012 and April 2016 and all of them were evaluated for safety and efficacy. Among them, 64 patients aged ≥65 years (55.2%) and five children aged <15 years (4.3%) were included. Of these patients, 47 (40.5%) met the approved indications of tigecycline. Adverse drug reactions (ADRs) were observed in 41 patients (35.3%) with a total of 74 events. Serious ADRs were observed in 15 patients (12.93%) with a total of 33 events. There were 42 deaths, and 6 of these were considered to be caused by ADRs. Among the 116 patients, 65 achieved clinical response at the end of the observation period, and the efficacy rate was 73.9%. Furthermore, 46 patients were assessed as "cure" at the test of cure visit, and the cure rate was 59.0%. The eradication rate was 47.5% at the end of the observation period. Classified by pathogenic bacteria, the eradication rate of patients infected with the approved pathogens was 54.5%. CONCLUSIONS: Tigecycline was well-tolerated, and no additional safety concerns were noted. It was effective considering that most patients had poor physical conditions. The overall benefit-risk balance of tigecycline was favorable.

Characterization of 3-isopropylmalate dehydrogenase from extremely halophilic archaeon Haloarcula japonica.

3-Isopropylmalate dehydrogenase (IPMDH) catalyzes oxidative decarboxylation of (2R, 3S)-3-isopropylmalate to 2-oxoisocaproate in leucine biosynthesis. In this study, recombinant IPMDH (HjIPMDH) from an extremely halophilic archaeon, Haloarcula japonica TR-1, was characterized. Activity of HjIPMDH increased as KCl concentration increased, and the maximum activity was observed at 3.0 m KCl. Analytical ultracentrifugation revealed that HjIPMDH formed a homotetramer at high KCl concentrations, and it dissociated to a monomer at low KCl concentrations. Additionally, HjIPMDH was thermally stabilized by higher KCl concentrations. This is the first report on haloarchaeal IPMDH.

Post-marketing surveillance of high-dose methotrexate (>8 mg/week) in Japanese patients with rheumatoid arthritis: A post hoc sub-analysis of patients according to duration of prior methotrexate use.

OBJECTIVES: To explore whether the duration of prior low-dose methotrexate treatment (MTX; ≤8 mg/week) influences the safety and effectiveness of high-dose MTX (>8 mg/week) in Japanese patients with rheumatoid arthritis (RA). METHODS: This post hoc sub-analysis of a Japanese post-marketing surveillance study evaluated patients initiating high-dose MTX with ≥1 year or <1 year prior low-dose MTX use. Over 24 or 52 weeks, adverse drug reactions (ADRs) were monitored, and effectiveness was assessed using the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4 (ESR)]. RESULTS: One thousand two hundred and ninety-two MTX ≥1 year and 1001 MTX <1 year patients were included. The incidence of ADRs during the 24- and 52-week follow-up period was significantly more frequent in MTX <1 year than ≥1 year patients and serious ADRs were significantly higher in MTX <1 year than ≥1 year patients during the 52-week follow-up period (all p < .05). Over both follow-up periods, the mean DAS28-4 (ESR) significantly decreased from baseline for all groups. Remission and low disease activity rates (DAS28-4 (ESR) <2.6 and <3.2, respectively) increased from baseline for all groups. CONCLUSION: High-dose MTX reduced disease activity regardless of prior treatment duration, but ADRs occurred more frequently among MTX <1 year patients compared to MTX ≥1 year patients.

Radiographic and clinical effects of 10 mg and 25 mg twice-weekly etanercept over 52 weeks in Japanese patients with active rheumatoid arthritis.

OBJECTIVES: To compare the radiographic and clinical effects of 25 versus 10 mg twice-weekly (BIW) etanercept over 52 weeks in Japanese patients with active rheumatoid arthritis (RA). METHODS: This was a post-hoc analysis of a Phase 3 study where Japanese patients with active RA were randomized to receive BIW etanercept 25 mg (n = 182), etanercept 10 mg (n = 192), or methotrexate (n = 176) for 52 weeks (NCT00445770). This analysis included assessments of week-24 and week-52 disease activity, week-52 radiographic progression, and the relationship between baseline characteristics and week 52 clinical outcomes with clinically relevant radiographic progression (CRRP) at week 52. RESULTS: At week 52, there were no significant differences between 25 and 10 mg etanercept in terms of achieving low disease activity or remission. CRRP was observed in 36% and 32% of patients in the 10 and 25 mg groups, respectively. Predictor analysis suggested that worse background disease status, treatment with methotrexate rather than etanercept, and poorer clinical outcomes at week 52 were associated with CRRP. CONCLUSIONS: The 25 mg BIW etanercept dosage does not appear to be significantly more efficacious than 10 mg in Japanese patients with RA. Further studies evaluating the optimal etanercept dosing regimen in this patient population may be merited. NCT: NCT00445770.

Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthritis: a postmarketing surveillance report.

Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan.Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted.Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24 and 52-week follow-up groups, respectively. Incidence of adverse drug reactions (ADRs) and serious ADRs was 21.42 and 1.66% in the 24-week and 35.52 and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-week (4.09-3.21) and 52-week treatment (3.91-2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS28-4ESR <2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24 weeks).Conclusion: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.

Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexate-naïve patients with active rheumatoid arthritis.

Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR).Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde's modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI).Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or <2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated.Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients.ClinicalTrials.gov identifierNCT00445770.

Contribution of Diabetes to the Incidence and Prevalence of Comorbid Conditions (Cancer, Periodontal Disease, Fracture, Impaired Cognitive Function, and Depression): A Systematic Review of Epidemiological Studies in Japanese Populations.

BACKGROUND: Several epidemiological studies have determined the relationship between diabetes and the incidence and/or prevalence of recently identified comorbid conditions (cancer, periodontal disease, fracture, cognitive impairment, and depression). These relationships may vary by country or race/ethnicity. We aimed to systematically review studies in this field conducted with the Japanese population because such a review in the Japanese population has never been undertaken. METHODS: We conducted systematic literature searches in PubMed and Ichushi-Web databases for studies published until December 2016. Studies comparing the incidence and/or prevalence of the comorbidities among the Japanese population were included. The studies were classified as integrated analyses, cohort studies, case-control studies, or cross-sectional studies. RESULTS: We identified 33 studies (cancer: 17, periodontal disease: 5, fracture: 5, cognitive impairment: 4, and depression: 2). Although several cohort studies and meta-analyses had assessed the development of cancer in diabetes, there was scant epidemiological evidence for the other conditions. Indeed, only one cohort study each had been conducted for periodontal disease, fracture, and cognitive impairment, whereas other evidence was cross-sectional, some of which was induced from baseline characteristic tables of studies designed for other purposes. CONCLUSION: In Japan, there is insufficient evidence about the relationship between diabetes and the incidence/prevalence of periodontal disease, fracture, cognitive impairment, and depression. By contrast, several cohort studies and integrated analyses have been conducted for the relationship with cancer. Further studies should be undertaken to estimate the contribution of diabetes on the incidence/prevalence of comorbidities that may be specific to the Japanese population.

Three-year safety and two-year effectiveness of etanercept in patients with rheumatoid arthritis in Japan: Results of long-term postmarketing surveillance.

Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.

Safety and effectiveness of etanercept for treatment of juvenile idiopathic arthritis: Results from a postmarketing surveillance.

OBJECTIVES: The objectives of this surveillance were to determine safety and effectiveness of etanercept in patients with juvenile idiopathic arthritis (JIA). METHODS: In this postmarketing surveillance, patients aged 5-16 years with active polyarthritis JIA were treated with etanercept at the doses approved in the Japanese package insert. The occurrence and seriousness of adverse events (AEs) were assessed using the Japanese Medical Dictionary for Regulatory Activities version 15.1. Effectiveness was determined as the improvement from baseline in disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), remission, and physician's assessment of overall improvement. The number of responders was expressed as a percentage. The last observation carried forward method was used to impute missing data. RESULTS: Safety analysis included 102 patients; 22 patients experienced 36 treatment-related AEs, three of which were unexpected. None of the AEs were deemed to need special safety warnings. Effectiveness analysis included 87 patients. At 24 weeks, 29/46 (63.0%) patients demonstrated either good or moderate response in DAS28-4/ESR and treatment was assessed to be markedly effective or effective by physicians in 79/83 (95.2%) patients. CONCLUSIONS: These data are consistent with earlier reports showing that etanercept was effective and demonstrated no safety signals in patients with JIA.

Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m2, and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials.

Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.

A case of type 2 diabetes mellitus with weight gain and worsening of glycemic management after tezepelumab administration for severe bronchial asthma.

Some cases of bronchial asthma are refractory to conventional therapies. As the pathogenesis of bronchial asthma has been clarified, new treatments, such as bronchial thermoplasty and biological drugs, have been developed. Tezepelumab, an anti-thymic stromal lymphopoietin antibody, has been reported to inhibit the exacerbation of severe asthma; however, its adverse effects on glucose metabolism have not yet been reported. We encountered a case of weight gain and worsening glycemic management in a patient with type 2 diabetes and refractory bronchial asthma after the initiation of tezepelumab treatment. It has been reported that the overexpression of thymic stromal lymphopoietin in mice resulted in an enhanced release of free fatty acids from adipose tissues and the liver; thus, the administration of anti-thymic stromal lymphopoietin antibodies in the present case might have caused obesity, fatty liver and lower glucose tolerance.

Implementation rate of diabetic self-management education and support for Japanese people with diabetes using the National Database.

People with diabetes are encouraged to receive diabetes self-management education and support (DSMES) appropriately. However, in Japan, the implementation rates of DSMES are not known. DSMES implementation rates were calculated using the National Database of claims data, which included nearly all insurance-covered medical procedures. The study enrolled participants who received regular antidiabetic medications between April 2017 and March 2018. The implementation rates of DSMES-related care were calculated by characteristics, visiting medical facilities and prefectures. In 4,465,513 participants receiving antidiabetic medications (men, 57.8%; insulin use, 14.1%), nutrition guidance (5.6%) was the most frequently provided care type. Insulin users and participants visiting Japan Diabetes Society-certified and large medical institutions had higher implementation rates of nutrition guidance. DSMES-related care might not be provided adequately for Japanese people with diabetes. Further studies are needed to develop an optimal diabetes care system.

Evaluation of a program designed to prevent diabetic nephropathy aggravation: A retrospective cohort study using health checkups and claims data in Japanese municipalities.

AIMS: Japan started the Diabetic Nephropathy Aggravation Prevention Program. Its early impact was assessed in this study. METHODS: This study used the Kokuho Database of patients with type 2 diabetes from program-implementing and non-implementing municipalities (fiscal years [FYs] 2015-2021). Implementing municipalities facilitated clinic visits and provided education to eligible patients. Average treatment effects on the treated in FYs 2016 and 2018 were evaluated using the inverse probability of treatment weighting. Comparison included intervened vs. non-intervened patients in program-implementing municipalities (Comparison A), intervened patients in program-implementing vs. eligible patients in non-implementing municipalities (Comparison B), and eligible patients in implementing and non-implementing municipalities (Comparison C). RESULTS: Overall, 89,611/89,685 patients from FY 2016/2018 were eligible. Among 68,125/68,170 patients in program-implementing municipalities, 1,470/1,819 were intervened. In Comparison A, the estimated effect of the program on ΔeGFR at 3 years were -0.4 (95 % confidence interval; -1.0, 0.2)/-0.4 (-0.9, 0.1) mL/min/1.73 m2 in FY 2016/2018. Comparisons B and C demonstrated similar tendency; distribution of %change in eGFR varied between municipalities. CONCLUSIONS: Early in the program, renal function did not improve in the intervened patients or program-implementing municipalities. Diverse eGFR changes across municipalities highlighted diverse intervention outcomes, emphasizing the need of program refinement.

Associations between income/employment status and diabetes care processes, health behaviors, and health outcomes in Japan: A cross-sectional study using claims data linked to a questionnaire survey.

AIMS/INTRODUCTION: We aimed to explore the associations between income/employment status and diabetes care processes, health behaviors and health outcomes. MATERIALS AND METHODS: This cross-sectional study used health insurance claims data between April 2021 and March 2022, and a questionnaire survey between December 2022 and January 2023 in Tsukuba City. The study analyzed the participants with diabetes (other than type 1) from those selected by stratified random sampling. We evaluated diabetes care processes, health behaviors and health outcomes by calculating weighted proportions among the groups. We also assessed the associations between income/employment status and these variables using multivariable modified Poisson regression models. RESULTS: Of the 264 identified participants, 161 (64.2%) were men and 168 (72.8%) were aged ≥65 years old. Compared with the low-income groups, the high-income group had a higher proportion of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists use (adjusted risk ratio [aRR] 1.70, 95% confidence interval (CI) 1.07-2.72), a higher proportion of attendance to annual health checkups for ≥2 years (aRR 1.68, 95% CI 1.07-2.64) and a lower proportion of all-cause hospitalization (aRR 0.15, 95% CI 0.04-0.48); additionally, the middle-income group had a lower proportion of high total outpatient medical expenses (aRR 0.57, 95% CI 0.35-0.92). Compared to the no work time group, the full-time work group had a lower proportion of exercise habits (aRR 0.59, 95% CI 0.35-0.99) and a higher proportion of good self-reported health (aRR 2.08, 95% CI 1.22-3.55). CONCLUSIONS: Several variables were associated with income/employment status. Policy intervention should focus on high-risk groups identified by considering these associations.

Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study.

AIMS/INTRODUCTION: A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk. MATERIALS AND METHODS: This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods. RESULTS: Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97-1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98-1.04). Findings were also consistent across cancer types and sensitivity analyses. CONCLUSIONS: We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.

Literature Review of Studies Using the National Database of the Health Insurance Claims of Japan (NDB): Limitations and Strategies in Using the NDB for Research.

The use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) for research has increased over time. Researchers need to understand the characteristics of the data to generate quality-assured evidence from the NDB. In this review, we mapped and characterized the limitations and related strategies using the NDB for research based on the descriptions of published NDB studies. To find studies that used Japanese healthcare claims data, we searched MEDLINE, EMBASE, and Ichushi-Web up to June 2023. Additionally, we hand-searched the NDB data publication list from the Ministry of Health, Labour and Welfare (2017-2023). We abstracted data based on the NDB data type, research themes, age of the study sample or population, targeted disease, and the limitations and strategies in the NDB studies. Ultimately, 267 studies were included. Overall, the most common research theme was describing and estimating the prescriptions and treatment patterns (125 studies, 46.8%). There was a variation in the frequency of themes according to the type of NDB data. We identified the following categories of limitations: (1) lack of information on confounders/covariates, outcomes, and other clinical content, (2) limitations regarding patients not included in the NDB, (3) misclassification of data, (4) lack of unique identifiers and register of beneficiaries, and (5) others. Although the included studies noted several limitations of using the NDB for research, they also provided some strategies to address them. Organizing the limitations of NDB in research and the related strategies across research fields can help support high-quality NDB studies.

Clinical significance of tumor markers in patients with type 2 diabetes: a retrospective observational study.

Aim: To cross-sectionally and longitudinally investigate the association between tumor markers (Cancer embryonic antigen (CEA) Carbohydrate antigen 19-9 (CA19-9)) and malignancies in type 2 diabetes patients without evidence of malignancy. Materials and Methods: The study included 707 patients admitted for the treatment of diabetes from 1 August 2010 to 1 September 2018. Serum CEA and CA19-9 levels were measured for screening of malignancies at admission. Abdominal ultrasonography, computed tomography, and endoscopy were performed for close examination. The percentage of patients diagnosed with malignancy was calculated, and among those without malignancy, the incidence of malignancies was examined after discharge. Results: A total of 26 patients (3.7%) were newly diagnosed with malignancy during hospitalization. The optimal cut-off value of CEA and CA19-9 by receiver operating characteristic analysis was 5.0 ng/mL and 75 U/mL, and their positive predictive values (PPV) were 8.7% and 22.5%, respectively. The addition of CA19-9 to age, smoking status, body mass index, and glycated hemoglobin significantly improved classification performance for malignancy using net reclassification improvement (0.682, 95% CI 0.256-1.107) and integrated discrimination improvement (0.150, 95% CI 0.007-0.294). Among 681 patients without malignancies during hospitalization, 30 patients (4.4%) developed malignancies during an average follow-up of 3.9 years. CA19-9 (hazard ratio: 1.005, 95% CI: 1.003-1.008) was associated with the development of malignancies. Conclusions: PPV of serum CEA and CA19-9 for detecting malignancy was high in type 2 diabetes patients with poor glycemic control. Measuring CA19-9 was found to be valuable to cross-sectionally and longitudinally detect malignancies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00594-x.

Proportion of subsequent clinic visits among persons without regular clinic visits who were screened as having hyperglycemia: A retrospective cohort study.

AIMS/INTRODUCTION: We aimed to examine the proportion of subsequent clinic visits for persons screened as having hyperglycemia based on glycated hemoglobin (HbA1c) levels at screening and the presence/absence of hyperglycemia at health checkups before 1 year of the screening among those without previous diabetes-related medical care and attending regular clinic visits. MATERIALS AND METHODS: This retrospective cohort study used the 2016-2020 data of Japanese health checkups and claims. The study analyzed 8,834 adult beneficiaries aged 20-59 years without regular clinic visits who had never received diabetes-related medical care and whose recent health checkups showed hyperglycemia. The rates of 6-month subsequent clinic visits after health checkups were evaluated according to HbA1c levels and the presence/absence of hyperglycemia at checkups a year before. RESULTS: The overall clinic visit rate was 21.0%. The HbA1c-specific rates were 17.0, 26.7, 25.4 and 28.4% for <7.0, 7.0-7.4, 7.5-7.9 and ≥8.0% (64 mmol/mol), respectively. Persons with hyperglycemia at a previous screening had lower clinic visit rates than those without hyperglycemia, particularly in the HbA1c category of <7.0% (14.4% vs 18.5%; P < 0.001) and 7.0-7.4% (23.6% vs 35.1%; P < 0.001). CONCLUSIONS: The overall rate of subsequent clinic visits among those without previous regular clinic visits was <30%, including for participants with HbA1c ≥8.0%. Persons with previously detected hyperglycemia had lower clinic visit rates, despite requiring more health counseling. Our findings might be useful for designing a tailored approach to encourage high-risk individuals to seek diabetes care through clinic visits.