Safety of advanced laparoscopic hepatectomy for elderly patients: a Japanese nationwide analysis.

BACKGROUND: Although basic laparoscopic hepatectomy (LH) has become the standard procedure for hepatectomy, the safety of advanced LH remains to be clarified, especially in elderly patients. We investigated the safety of advanced LH in elderly Japanese patients. METHODS: Elderly patients (≥ 65 years) who underwent advanced LH between 2016 and 2021 were analyzed using a nationwide claims database in Japan. The perioperative outcomes of patients who underwent open hepatectomy (OH group) or LH (LH group) were compared using propensity score matching (PSM). The primary outcome was in-hospital mortality. The E-value method was performed to assess the strength of the outcome point estimates against possible unmeasured confounding factors. RESULTS: Among 5,021 patients, eligible patients were classified into the OH (n = 4,152) and LH (n = 527) groups. The median patient age was 74 years in both groups. Hepatocellular carcinoma and metastatic liver tumors were the major indications for hepatectomy (OH: 52.5% versus 30.6%; LH: 60.7% versus 26.4%). After PSM, in-hospital mortality rates for OH and LH were 1.7 and 0.76%, respectively. The risk ratio was 0.45 (95% confidence interval, 0.16-1.25; E-value = 3.87). Compared with OH, LH was associated with a longer anesthesia time (411 versus 432 min), lower rate of blood product use (red blood concentrate: 33.5% versus 20.3%; fresh frozen plasma: 29.2% versus 17.1%), and shorter hospital stay (13 versus 12 days). CONCLUSIONS: In elderly patients, the safety of advanced LH was similar to that of advanced OH, or might be better in Japan under the current policy of hospital accreditation.

Treatment for patients with autosomal dominant polycystic kidney disease in the chronic kidney disease without kidney replacement therapy in real-world clinical practice: a descriptive retrospective cohort study.

BACKGROUND: In real-world clinical practice, treatments selected for patients with autosomal dominant polycystic kidney disease (ADPKD) in the chronic kidney disease (CKD) without kidney replacement therapy (KRT) have not been reported. This study investigated the oral treatments used in these patients and the changes in their use in recent years. Additionally, we studied the factors affecting tolvaptan dose reduction or discontinuation. METHODS: This retrospective cohort study was conducted using the medical records of 160 hospitals in Japan. Patients with ADPKD or polycystic kidney disease registered on the database between January 2014 and December 2020 were selected. Changes in prescription proportions over time were assessed using the Cochran-Armitage test. We focused on patients prescribed with >15 mg of tolvaptan daily to identify the factors related to its dose reduction or discontinuation and used Multivariate Cox regression analysis to evaluate them. RESULTS: Tolvaptan use in patients with ADPKD in the CKD without KRT stage has increased. As of 2020, 25% of patients were treated with tolvaptan. Overall, 3639 patients with ADPKD were enrolled in the database, of whom 156 were treated with tolvaptan. Of these, 64 patients (41%) reduced or discontinued tolvaptan during the observation period. The presence of an estimated glomerular filtration rate <60 mL/min/1.73 m2 at the beginning of the treatment was associated with a higher risk of tolvaptan dose reduction or discontinuation. CONCLUSION: The proportion of patients with ADPKD treated with high-dose tolvaptan is increasing. However, patients with late-stage CKD tended to reduce or discontinue tolvaptan.

Effect of multidisciplinary care on diabetic kidney disease: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) is the most common disease among patients requiring dialysis for the first time in Japan. Multidisciplinary care (MDC) may prevent the progression of kidney failure. However, the effectiveness and timing of MDC to preserve kidney function in patients with DKD is unclear. Therefore, the aim of this study was to investigate whether MDC for patients with DKD affects the preservation of kidney function as well as the timing of MDC in clinical practice. METHODS: In this retrospective cohort study, we identified patients with type 2 diabetes mellitus and DKD from April 2012 to January 2020 using a nationwide Japanese healthcare record database. The fee code for medical guidance to prevent dialysis in patients with diabetes was used to distinguish between the MDC and non-MDC groups. The primary outcome was a 40% decline in the estimated glomerular filtration rate, and secondary outcomes were death, hospitalization, permanent dialysis, kidney failure with replacement therapy, and emergency temporary catheterization. Propensity score matching was performed, and Kaplan-Meier and multivariable Cox regression analyses were performed. RESULTS: Overall, 9,804 eligible patients met the inclusion criteria, of whom 5,614 were matched for the main analysis: 1,039 in the MDC group, and 4,575 in the non-MDC group. The primary outcome did not differ between the groups (hazard ratio: 1.18, [95% confidence interval: 0.99-1.41], P = 0.07). The groups also did not differ in terms of the secondary outcomes. Most patients with DKD received their first MDC guidance within 1 month of diagnosis, but most received guidance only once per year. CONCLUSIONS: Although we could not demonstrate the effectiveness of MDC on kidney function in patients with DKD, we clarified the characteristics of such patients assigned the fee code for medical guidance to prevent dialysis related to diabetes.

Functional opsin patterning for Drosophila color vision is established through signaling pathways in adjacent object-detection neurons.

Vision is mainly based on two different tasks, object detection and color discrimination, carried out by photoreceptor (PR) cells. The Drosophila compound eye consists of ∼800 ommatidia. Every ommatidium contains eight PR cells, six outer cells (R1-R6) and two inner cells (R7 and R8), by which object detection and color vision are achieved, respectively. Expression of opsin genes in R7 and R8 is highly coordinated through the instructive signal from R7 to R8, and two major ommatidial subtypes are distributed stochastically; pale type expresses Rh3/Rh5 and yellow type expresses Rh4/Rh6 in R7/R8. The homeodomain protein Defective proventriculus (Dve) is expressed in yellow-type R7 and in six outer PRs, and it is involved in Rh3 repression to specify the yellow-type R7. dve mutant eyes exhibited atypical coupling, Rh3/Rh6 and Rh4/Rh5, indicating that Dve activity is required for proper opsin coupling. Surprisingly, Dve activity in R1 is required for the instructive signal, whereas activity in R6 and R7 blocks the signal. Our results indicate that functional coupling of two different neurons is established through signaling pathways from adjacent neurons that are functionally different.

Timing of Initiation of Xanthine Oxidase Inhibitors Based on Serum Uric Acid Level Does Not Predict Renoprognosis in Patients with Preserved Kidney Function.

Background: Despite recent evidence of remaining possibility that early initiation of xanthine oxidase inhibitors (XOIs) is beneficial in renoprognosis for patients with stage 2 or less chronic kidney disease (CKD), no evidence is available regarding the difference in renoprognosis based on serum uric acid (sUA) levels at the initiation of XOIs among patients with preserved kidney function. Methods: New XOI initiators were divided into quartiles based on baseline sUA. Primary outcome was the composite incidence of a significant estimated glomerular filtration rate (eGFR) decline (≥40% decline in eGFR from baseline or development of eGFR <30 mL/1.73 m2/min) or all-cause death within 5 years. Results: After excluding inapplicable patients, 1170 XOI initiators were analyzed (mean ± standard deviation age: 68 ± 14.3 years; sUA: 10.6 ± 1.15 mg/dL). On overall median [interquartile range (IQR)] follow-up of 824 (342, 1576) days, incidence rate of the primary outcome was 287 per 1000 person-years for 5 years. Although the nonadjusted model showed a dose-response association between baseline sUA level and the outcome, the adjusted model showed no significant association. Adjusted hazard ratios (95% confidence interval) of the second, third, and fourth quartiles of baseline sUA with the composite outcome within 5 years compared to the first quartile were 1.00 (0.78, 1.29), 1.00 (0.80, 1.30), and 1.02 (0.80, 1.32), respectively. Conclusions: Early initiation of XOIs did not predict a significant benefit on renoprognosis even among the population with preserved kidney function. The validity of initiating XOIs with the aim of improving renoprognosis based on sUA is questionable.

Effectiveness of sublingual immunotherapy in pediatric cedar pollinosis: A real-world database study.

BACKGROUND: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real-world settings, on children with CP. METHODS: This retrospective cohort study used a claim database in 2018-2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. RESULTS: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non-SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was -0.62 (95% confidence interval: -0.86 to -0.39, p < .0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. CONCLUSION: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases.

Cardiovascular Safety of Atomoxetine and Methylphenidate in Patients With Attention-Deficit/Hyperactivity Disorder in Japan: A Self-Controlled Case Series Study.

OBJECTIVE: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. METHODS: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. RESULTS: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. CONCLUSIONS: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.

Association between sedation during spinal anesthesia and mortality in older patients undergoing hip fracture surgery: A nationwide retrospective cohort study in Japan.

STUDY OBJECTIVE: Intraoperative sedation plays an important role in the management of regional anesthesia. Few studies have investigated the association of sedation during spinal anesthesia with postoperative mortality in older patients as a primary outcome. This study aimed to test the hypothesis that sedation during spinal anesthesia increases postoperative mortality in older patients undergoing hip fracture surgery. DESIGN: Retrospective, cohort study. SETTING: Acute and subacute care hospitals in Japan. PATIENTS: Patients aged 65 years and older who received hip fracture surgery under spinal anesthesia between April 2014 and May 2022. EXPOSURE: Sedation during spinal anesthesia. MEASUREMENTS: Postoperative in-hospital all-cause mortality within 30 days. MAIN RESULTS: In total, 25,554 eligible patients were identified. Propensity score matching created 4735 pairs, and baseline patient characteristics were acceptably balanced between the sedation and non-sedation groups. There was no significant difference in 30-day postoperative mortality between the two groups (hazard ratio [95% CIs]: 0.92 [0.59-1.44]). CONCLUSIONS: There was no association between sedation during hip fracture surgery in older patients under spinal anesthesia and postoperative mortality. However, these results are limited to our population, and further prospective studies are needed to determine the safety of sedation.

Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism Receiving Edoxaban in the Real World.

BACKGROUND: The effectiveness and safety of edoxaban for venous thromboembolism (VTE) in unselected real-world patients have not been fully evaluated.Methods and Results: In the Japanese nationwide administrative database, we identified 6,262 VTE patients in whom edoxaban was initiated; these patients were divided into 3 groups based on their index doses: 15 mg/day (n=235), 30 mg/day (n=4,532), and 60 mg/day (n=1,495). We evaluated patient characteristics, recurrent VTEs, and a composite endpoint of intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding. Patient characteristics among the 15-, 30-, and 60-mg edoxaban groups varied widely regarding several aspects, including age (mean 81.0, 76.2, and 65.0 years, respectively) and body weight (mean 49.5, 51.8, and 70.3 kg, respectively). At 180 days, the cumulative incidence of recurrent VTEs in the 15-, 30-, and 60-mg edoxaban groups was 4.4%, 2.6%, and 1.8%, respectively, whereas that of ICH or GI bleeding was 7.3%, 5.4%, and 3.3%, respectively. Subgroup analyses showed that the cumulative incidence of ICH or GI bleeding in patients in the 15-mg edoxaban group was 3.6% for patients aged ≥80 years, 8.4% for those with a body weight <60 kg, and 31.3% for those with renal dysfunction. CONCLUSIONS: Only a minority of patients with VTEs received a super low dose (15 mg) of edoxaban, and these patients may be at higher risk of bleeding as well as VTE recurrence.

Frequency and determinants of serum calcium monitoring during eldecalcitol therapy in patients with osteoporosis.

INTRODUCTION: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. MATERIALS AND METHODS: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. RESULTS: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. CONCLUSION: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice.

Prediction models for in-hospital deaths of patients with COVID-19 using electronic healthcare data.

OBJECTIVE: Many models for predicting various disease prognoses have achieved high performance without laboratory test results. However, whether laboratory test results can improve performance remains unclear. This study aimed to investigate whether laboratory test results improve the model performance for coronavirus disease 2019 (COVID-19). METHODS: Prediction models were developed using data from the electronic healthcare record database in Japan. Patients aged ≥18 years hospitalized for COVID-19 after February 11, 2020, were included. Their age, sex, comorbidities, laboratory test results, and number of days from February 11, 2020, were collected. We developed a logistic regression, XGBOOST, random forest, and neural network analysis and compared the performance with and without laboratory test results. The performance of predicting in-hospital death was evaluated using the area under the curve (AUC). RESULTS: Data from 8,288 hospitalized patients (females, 46.5%) were analyzed. The median patient age was 71 years. A total of 6,630 patients were included in the training dataset, and 312 (4.7%) died. In the logistic regression model, the area under the curve was 0.88 (95% confidence interval [CI] = 0.83-0.93) and 0.75 (95% CI = 0.68-0.81) with and without laboratory test results, respectively. The performance was not fundamentally different between the model types, and the laboratory test results improved the performance in all cases. The variables useful for prediction were blood urea nitrogen, albumin, and lactate dehydrogenase. CONCLUSIONS: Laboratory test results, such as blood urea nitrogen, albumin, and lactate dehydrogenase levels, along with background information, helped estimate the prognosis of patients hospitalized for COVID-19.

Real-world practice of estrogen and progestogen prescriptions in menopausal women in Japan: A descriptive study using a Japanese claims database.

AIM: This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women. METHODS: Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed. RESULTS: In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021. CONCLUSIONS: This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women.

Are Dental Procedures Associated With Pyogenic Vertebral Osteomyelitis?

BACKGROUND: Dental procedures can lead to bacteremia and have been considered a potential risk factor for pyogenic vertebral osteomyelitis (PVO). However, data on the association between dental procedures and PVO are limited. QUESTIONS/PURPOSES: (1) After controlling for relevant confounding variables, are dental procedures associated with an increased risk of PVO? (2) Does antibiotic prophylaxis before dental procedures effectively decrease the risk of PVO? METHODS: A case-crossover study was conducted to investigate the association between dental procedures and PVO using a Japanese claims database. The advantage of this study design is that confounding factors that do not vary over time are automatically adjusted for, because cases act as their own controls. From April 2014 to September 2021, the database included 8414 patients who were hospitalized for PVO. Of these, 50% (4182 of 8414) were excluded because they had not undergone any dental procedures before the index date, a further 0.1% (10 of 8414) were excluded because they were younger than 18 years at the index date, and a further 7% (623 of 8414) were excluded because they did not have at least 20 weeks of continuous enrollment before the index date, leaving 43% (3599 of 8414) eligible for analysis here. The mean age was 77 ± 11 years, and 55% (1985 of 3599) were men. Sixty-five percent (2356 of 3599) of patients had a diagnosis of diabetes mellitus, and 42% (1519 of 3599) of patients had a diagnosis of osteoporosis. We compared the frequency of dental procedures between a 4-week hazard period before the admission date for PVO and two control periods, 9 to 12 weeks and 17 to 20 weeks before the admission date for PVO, within individuals. We calculated odds ratios and 95% confidence intervals using conditional logistic regression analysis. RESULTS: Comparing the hazard and matched control periods within individuals demonstrated that dental procedures were not associated with an increased risk of PVO (OR 0.81 [95% CI 0.72 to 0.92]; p < 0.001). Additional analysis stratified by antibiotic prophylaxis use showed that antibiotic prophylaxis was not associated with a lower OR of developing PVO after dental procedures (with antibiotic prophylaxis: OR 1.11 [95% CI 0.93 to 1.32]; p < 0.26, without antibiotic prophylaxis: OR 0.72 [95% CI 0.63 to 0.83]; p < 0.001). Our sensitivity analyses, in which the exposure assessment interval was extended from 4 to 8 or 12 weeks and exposure was stratified by whether the dental procedure was invasive, demonstrated results that were consistent with our main analysis. CONCLUSION: Dental procedures were not associated with an increased risk of subsequent PVO in this case-crossover study. The effectiveness of antibiotic prophylaxis was not demonstrated in the additional analysis that categorized exposure according to the use of antibiotic prophylaxis. Our results suggest that the association between dental procedures and PVO may have been overestimated. Maintaining good oral hygiene may be important in preventing the development of PVO. The indications for antibiotic prophylaxis before dental procedures should be reconsidered in view of the potential risk of adverse drug reactions to antibiotic prophylaxis and the emergence of drug-resistant pathogens. Larger randomized controlled trials are needed to confirm these findings and assess the role of antibiotic prophylaxis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Acute Coronary Spasm Following Pelvic Fracture, Bleeding, and Shock in a Trauma Patient.

We report a case of a patient with severe pelvic fracture who showed concurrent ST elevation on electrocardiogram. A 70-year-old man incurred an unstable pelvic fracture from a motorcycle accident. On admission, he was hemodynamically unstable, and massive transfusion and noradrenaline were administered immediately. Although ST elevation was present in leads II, III, aVF, V5, and V6, cardiac function was preserved; thus, trans-arterial embolization and external fixation for pelvic fracture were given priority. Four days after the injury, he suffered a cardiac arrest, and coronary angiography revealed that the cause of ST elevation and cardiac arrest was coronary vasospasm. Physicians should be aware that pain-related stress and platelet activation as well as use of noradrenaline in severe trauma cases can induce coronary vasospasm.

Association between dental procedures and periprosthetic joint infection: A case-crossover study.

BACKGROUND: Although the risk of dental procedures as a cause of bacteremia has been recognized, evidence regarding the association between dental procedures and late periprosthetic joint infection (LPJI) is scarce. We sought to determine whether dental procedures are associated with an increased risk of LPJI. METHODS: The study was conducted under a case-crossover design using a large claims database in Japan. We identified adult patients who had undergone dental procedures and were hospitalized for LPJI between April 2014 and September 2021. Exposure to dental procedures was assessed during a case period of 1-4 weeks, with two control periods of 9-12 weeks and 17-20 weeks, preceding LPJI hospital admission. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of LPJI associated with dental procedures in the case period compared with the two control periods. RESULTS: In total, 241 patients with LPJI were included in the case-crossover study. At least one dental procedure was performed in 46 patients (19.1%) in the hazard period and in 75 patients (31.1%) in the control periods. The OR for LPJI with dental procedures was 0.96 (95% CI, 0.61-1.53; p = 0.88). Findings were robust in several sensitivity analyses, including stratification by whether the dental procedure included antibiotic prophylaxis. CONCLUSIONS: This study suggests that dental procedures are not associated with increased risk of LPJI, and will raise questions about the recommendation for antibiotic prophylaxis before dental procedures.

Effectiveness of Specific Health Check-ups in Japan for the primary prevention of obesity-related diseases: a protocol for a target trial emulation.

INTRODUCTION: Concerns about public health threats have shifted towards obesity-related, non-communicable diseases in both developed and developing countries. Since 2008, Japan has adopted a nationwide universal screening programme called Specific Health check-ups (SHC) for the primary prevention of obesity-related, non-communicable diseases, namely, diabetes, hypertension and hyperlipidaemia. The effectiveness of SHC has not been systemically evaluated to date. METHODS AND ANALYSIS: We will use the employment-based health insurance database, which includes both records of receipt versus non-receipt of SHC and healthcare claims. The study design adopts the target trial emulation framework to minimise the bias inherent to the observational study (eg, time-related bias and its consequences). The key components of trial emulation-eligibility criteria, treatment strategy, assignment procedure, follow-up period, outcome, causal contrast of interest and analysis plan-are detailed, along with the ideal target trial protocol. Briefly, we will conduct the nested-trial emulation approach that allows multiple trial entries. Persons aged 40-74 years will be eligible if they do not have a documented diagnosis of hypertension and diabetes and a history of receiving SHC at baseline. Participants will be classified according to the receipt or non-receipt of SHC service and followed for a maximum of 10 years until the withdrawal from the insurance plan, the outcome occurrence or the administrative censoring (the end of the available data, expected to be March 2022), whichever comes first. The 10-year incidence of diabetes/hypertension will be compared between SHC recipients and non-recipients using pooled logistic regression with adjustments for baseline confounders. Five sensitivity analyses are employed, including per-protocol analysis, changing eligibility criteria and negative outcome control analysis. ETHICS AND DISSEMINATION: This protocol obtained the approval from Kyoto University Graduate School and Faculty of Medicine, Ethics Committee (R2448). The findings will be disseminated to academic conferences, and published in a peer-reviewed journal.

Does nutritional guidance reduce cardiovascular events in patients with type 2 diabetes mellitus? A retrospective cohort study using a nationwide claims database.

AIM: To examine the effect of nutritional guidance (NG) provided by a registered dietitian under the direction of a physician on the development of subsequent cardiovascular events in patients with early-stage type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This retrospective cohort study used the JMDC claims database to explore patients aged 18 years or older who first met the diagnostic criteria for T2DM at a health checkup between January 2011 and January 2019. The last day of the observation period was set for 28 February, 2021. Exposure was defined as receiving NG within 180 days of diagnosis of T2DM. The primary outcome was a composite endpoint of coronary artery disease (CAD) and cerebrovascular disease, and the secondary outcomes were each event, and time to event was compared. The propensity score weighting method was used for adjusting the distribution of confounding variables. Cox regression was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Overall, 31,378 patients met the eligibility criteria at an annual health checkup. 9.6% received NG (n = 3013). Patients who attended ≥ 1 NG after diagnosis had significantly reduced risk of cardiovascular composite (adjusted HR 0.75, 95% CI 0.58-0.97) and cerebrovascular disease (adjusted HR 0.65, 95% CI 0.47-0.90) during approximately 3.3 years of follow-up. In contrast, no difference was observed for CAD. CONCLUSIONS: Receiving NG in early-stage diabetes may reduce the incidence of cardiovascular events, especially cerebrovascular events.

Association between urate-lowering therapy and cardiovascular events in patients with asymptomatic hyperuricemia.

INTRODUCTION/OBJECTIVES: To investigate the role of urate-lowering therapy (ULT) in the prevention of cardiovascular disease (CVD) in patients with asymptomatic hyperuricemia using the Japanese healthcare record database. METHODS: This retrospective cohort study used data from the JMDC Claims Database, which includes records of medical check-ups and Japanese health insurance claims. Subjects aged at least 18 years with a serum uric acid (sUA) level ≥ 7.0 mg/dL and at least one medical check-up from January 2007 to August 2021 were included in this study. The exposure was any ULT prescription, and the primary outcome included composite CVD outcomes, including coronary artery disease, stroke, and atrial fibrillation. Analysis was performed with a new-user design and overlap weighting to balance the baseline characteristics of the subjects. Cox proportional hazards models were used to investigate the association between ULT and the development of CVD. RESULTS: In total, 152,166 patients were included in the main analysis before overlap weighting in this retrospective cohort study. The number of subjects in the ULT group was 5,270, and there were 146,896 subjects in the control group. Composite CVD outcomes were observed in a total of 7,703 patients. The risk of developing composite CVD outcomes was not different between the ULT group and the control group (HR: 1.01, 95% CI: 0.89 to 1.13). CONCLUSIONS: ULT for patients with asymptomatic hyperuricemia did not prevent the development of CVD based on the Japanese claims database. Key points • Among subjects with asymptomatic hyperuricemia, ULT was not associated with a lower risk of CVD • There was no appropriate cutoff for initiating ULT in patients with asymptomatic hyperuricemia • There was no appropriate cutoff as the therapeutic goal of ULT in patients with asymptomatic hyperuricemia.