Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial.

BACKGROUND: Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. Clinically, SP/MC has a slower post-dose defaecation response than PEG and is perceived as less cleansing; therefore, it is not currently used for major bowel cancer screening preparation. The standard formulation for bowel preparation is PEG; however, a large dose is required, and it has a distinctive flavour that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical trials have shown that SP/MC is superior to PEG in terms of acceptability. We aim to compare the novel bowel cleansing method (test group) comprising SP/MC with elobixibat hydrate and the standard bowel cleansing method comprising PEG plus ascorbic acid (standard group) for patients preparing for outpatient colonoscopy. METHODS: This phase III, multicentre, single-blind, noninferiority, randomised, controlled, trial has not yet been completed. Patients aged 40-69 years will be included as participants. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction will be excluded. The target number of research participants is 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint is the degree of bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥ 6). The secondary endpoints are patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to the BBPS (BBPS score ≥ 8), degree of bowel cleansing according to the Aronchik scale, and bowel cleansing time. DISCUSSION: This trial aims to develop a "patient-first" colon cleansing regimen without the risk of inadequate bowel preparation by using both elobixibat hydrate and SP/MC. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; no. s041210067; 9 September 2021; https://jrct.niph.go.jp/ ), protocol version 1.5 (May 1, 2023).

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Venous thromboembolism in patients undergoing surgery for lung cancer: a post hoc analysis of the Cancer-VTE Registry.

The relationship between lung cancer surgery and venous thromboembolism (VTE) in Japan has not been elucidated. This was a post hoc analysis of the Cancer-VTE Registry. The 1057 patients who underwent surgery for lung cancer were divided into the surgery alone (SA) group (n = 598) and the surgery plus chemotherapy (SC) group (n = 459), and the 1-year incidences of VTE and cerebral ischemia were analyzed. In the SA and SC groups, composite VTE was observed in one (0.2%) and 15 (3.3%) patients, respectively, and cerebral ischemia was observed in eight (1.3%) and four (0.9%) patients, respectively. Lymph node metastasis was more common in patients with D-dimer >1.2 µg/ml (odds ratio: 1.781, P = .004). SA had a low risk of VTE but a high risk of cerebral ischemia. Chemotherapy increases the risk of VTE. The D-dimer level was related to VTE and advanced cancer.

Association of D-dimer level with thrombotic events, bleeding, and mortality in Japanese patients with solid tumors: a Cancer-VTE Registry subanalysis.

BACKGROUND: The D-dimer test is a simple test frequently used in routine clinical screening for venous thromboembolism (VTE). The Cancer-VTE Registry was a large-scale, multicenter, prospective, observational study in Japanese patients with cancer. This study aimed to clarify the relationship between D-dimer level at cancer diagnosis (baseline) and the incidence of events during cancer treatment (1-year follow-up period). METHODS: This was a post hoc sub-analysis of patients from the Cancer-VTE Registry whose D-dimer levels were measured at baseline. The incidence of events during the 1-year follow-up period was evaluated stratified by baseline D-dimer level. Adjusted hazard ratios for D-dimer level and events during the follow-up period were evaluated. RESULTS: Among the total enrolled patients, baseline D-dimer level was measured in 9020 patients. The mean ± standard deviation baseline D-dimer level was 1.57 ± 3.94 µg/mL. During the follow-up period, the incidence of VTE, cerebral infarction/transient ischemic attack (TIA)/systemic embolic events (SEE), bleeding, and all-cause death increased with increasing baseline D-dimer level. The incidence of all-cause death increased with increasing D-dimer level regardless of cancer stage. The adjusted hazard ratio of all-cause death was 1.03 (95% confidence interval: 1.02-1.03) per 1.0-µg/mL increase in baseline D-dimer level. CONCLUSIONS: Increases in D-dimer levels were associated with a higher risk of thrombotic events, such as VTE and cerebral infarction/TIA/SEE, during cancer treatment. Furthermore, higher D-dimer levels at cancer diagnosis were associated with a higher mortality rate, regardless of cancer stage.

Fulvestrant plus palbociclib in advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer after fulvestrant monotherapy: Japan Breast Cancer Research Group-M07 (FUTURE trial).

PURPOSE: The combination of cyclin-dependent kinase 4/6 inhibitors and endocrine therapy is a standard treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC); however, their toxicities and financial burden are major issues, especially for prolonged treatment. We investigated fulvestrant plus palbociclib in patients with HR-positive MBC resistant to fulvestrant monotherapy. METHODS: Patients who initially received fulvestrant as their first- or second-line endocrine therapy were assigned to group A. Patients with disease progression during fulvestrant monotherapy who subsequently received fulvestrant plus palbociclib were assigned to group B. The primary endpoint was progression-free survival (PFS1) in group B. We set the threshold median PFS of 5 months (null hypothesis). RESULTS: Between January 2018 and February 2020 we enrolled 167 patients in group A (January 2018-February 2020) from 55 institutions, of whom 72 subsequently received fulvestrant plus palbociclib and were enrolled in group B. The median follow-up was 23.8 and 8.9 months in groups A and B, respectively. The median PFS in group B (combination therapy) was 9.4 (90% confidence interval [CI]: 6.9-11.2) months (p < 0.001). This was 25.7 (90% CI: 21.2-30.3) months in group A (fulvestrant monotherapy). The TTF in group B was 7.2 (90% CI: 5.5-10.4) months. In the post-hoc analysis, the median PFS1 in group B among patients with longer-duration fulvestrant monotherapy (> 1 year) was longer than that of patients with shorter-duration monotherapy (≤ 1 year) (11.3 vs. 7.6 months). No new toxicities were observed. CONCLUSION: Our findings suggest that palbociclib plus fulvestrant after disease progression despite fulvestrant monotherapy is potentially safe and effective in patients with HR-positive/HER2-negative advanced MBC.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry stomach cancer subcohort.

BACKGROUND: The Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry. METHODS: Stage II-IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled. RESULTS: Of 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 µg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21-2.32; p = 0.002). CONCLUSIONS: VTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy. TRIAL REGISTRATION: UMIN000024942.

Impact of renal and hepatic function on first opioid prescriptions in cancer patients: an acute care hospital database study linked to medical claims data and laboratory data.

BACKGROUND: Cancer patients often have impaired renal and hepatic function. Opioids are essential to relieve painful symptoms in cancer patients. However, it is unknown which opioids are first prescribed for cancer patients with renal and hepatic impairment. The objective is to investigate the association between the type of first prescribed opioids and the renal/hepatic function of cancer patients. METHODS: We used a multicenter database from 2010 to 2019. The number of days from the first opioid prescription to the death was defined as the prognostic period. This period was divided into six categories. The prevalence of opioid prescriptions was calculated for each assessment of renal and hepatic function, divided into prognostic periods. Multinomial logistic regression analysis was used to explore the influence of renal and hepatic function on the first opioid choice. RESULTS: The study included 11 945 patients who died of cancer. In all prognostic period categories, the patients with worse renal function received fewer morphine prescriptions. No trend was observed in hepatic function. The odds ratio of oxycodone to morphine with reference to estimated glomerular filtration rate (eGFR) ≥90 was 1.707 (95% confidence interval: 1.433-2.034) for estimated glomerular filtration rate <30. The odds ratio of fentanyl to morphine with reference to estimated glomerular filtration rate ≥90 was 1.785 (95% confidence interval: 1.492-2.134) for estimated glomerular filtration rate <30. No association was identified between hepatic function and the choice of prescribed opioids. CONCLUSION: Cancer patients with renal impairment tended to avoid morphine prescriptions, and no specific trend was observed in cancer patients with hepatic impairment.

Maintenance repetitive transcranial magnetic stimulation (rTMS) therapy for treatment-resistant depression: a study protocol of a multisite, prospective, non-randomized longitudinal study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a widely used treatment for major depressive disorder (MDD), and its effectiveness in preventing relapse/recurrence of MDD has been explored. Although few small sample controlled studies exist, the protocols of maintenance rTMS therapy were heterogeneous and evidence of its effectiveness is not sufficient. Thus, this study aims to evaluate whether maintenance rTMS is effective in maintaining the treatment response in patients with MDD with a large sample size and feasible study design. METHODS: In this multicenter open-labelled parallel-group trial we plan to recruit 300 patients with MDD who have responded or remitted to acute rTMS therapy. Participants would be classified into two groups according to their preference; the maintenance rTMS and pharmacotherapy group, and the pharmacotherapy only group. The protocol of maintenance rTMS therapy is once a week for the first six months and once biweekly for the second six months. The primary outcome is the relapse/recurrence rates during 12 months following enrollment. Other measures of depressive symptoms and recurrence/relapse rates at different time points are the secondary outcomes. The primary analysis is the between-group comparison adjusted for background factors using a logistic regression model. We will perform the group comparison with inverse probability of treatment weighting as the sensitivity analysis to ensure the comparability of the two groups. DISCUSSION: We hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering the limitation of potential bias owing to the study design, we plan to use statistical approaches and external data to avoid overestimation of the efficacy. TRIAL REGISTRATION: Japan Registry of Clinical Trials, ID: jRCT1032220048 . Registered 1 May 2022.

Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome.

BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

Incidence and risk factors for venous thromboembolism, bleeding, and death in colorectal cancer (Cancer-VTE Registry).

The impact of venous thromboembolism in Japanese colorectal cancer patients has not been elucidated. This prespecified subanalysis of the Cancer-VTE Registry aimed to report venous thromboembolism and event data after 1 year of follow-up in 2477 patients with colorectal cancer and investigate risk factors of venous thromboembolism. Of 2477 patients, 158 (6.4%) had venous thromboembolism in venous thromboembolism screening at enrollment. Asymptomatic distal deep-vein thrombosis accounted for 123/158 (77.8%) of venous thromboembolism cases. During the follow-up period, symptomatic, incidental events requiring treatment and composite venous thromboembolism incidences were 0.3%, 0.8%, and 1.0%, respectively. The incidence of bleeding events, cerebral infarction/transient ischemic attack/systemic embolic event, and all-cause death were 1.0%, 0.3%, and 4.8%, respectively. These results were consistent with the main study results. In multivariable analysis, venous thromboembolism at baseline was a risk factor of composite venous thromboembolism during the follow-up period. Japanese patients with colorectal cancer and advancing cancer stage before treatment had more frequent venous thromboembolism complications at baseline, higher incidence of venous thromboembolism events during cancer treatment, and higher mortality.

Trends in strong opioid prescription for cancer patients in Japan from 2010 to 2019: an analysis with large medical claims data.

BACKGROUND: Consumption of opioids, essential drugs for pain relief, has seen rapid growth worldwide. In Japan, where total opioid consumption still remains low among developed countries, little is known about trends in the clinical patterns of opioids in terminally ill cancer patients. METHODS: Patients who died of cancer from 2010 to 2019 were included in this study. Morphine, oxycodone, fentanyl, tapentadol, methadone and hydromorphone were examined as opioids for cancer pain. We calculated the prevalence of prescribed opioids prior to death by year and age group and the average opioid dose 30 days before death. RESULTS: The total number of patients was 221 598. We found that the prescription prevalence of opioids increased from 60.8 to 65.9% (5.1%). Morphine was most prescribed in 2010 but had decreased prevalence (-9.0%) during the 10-year period. Oxycodone had the highest increase in prescription prevalence (13.7%), and fentanyl prevalence decreased (-4.9%). In the subgroup comparison, the prescription prevalence of opioids in the elderly was lower than that in the younger group; however, the increasing trend in the elderly was greater than that in the younger group. The percentage of patients prescribed low-dose opioids (<60 mg/day) during the 30 days before death increased by 4.9% and was the highest throughout the study period. CONCLUSION: The prevalence of opioid prescriptions for terminally ill cancer patients has increased from 2010 to 2019 in Japan. The opioid-specific trends were similar to the global trend but differed by palliative care specialty.

The effects of post-frozen-thawed embryo transfer pregnancy on early fetal development.

AIM: Frozen-thawed embryo transfer (FET) has gained popularity as an assistive reproductive technology despite its increased risk of large-for-gestational-age offspring. This study aimed to analyze the effect of FET on fetal development, particularly the growth rate and estimated fetal weight (EFW) throughout pregnancy. METHODS: This was a single-center, retrospective study that examined 97 patients with FET conception and 477 patients with natural conception (NC) who underwent labor and delivery at our clinic between December 2015 and June 2019. Crown-rump length (CRL) in the first trimester and EFW measurements in the second and third trimesters were obtained from transabdominal ultrasound records. Birthweight was adjusted for sex, parity, and gestational age. Regression coefficients of CRL, EFW, and birthweight were compared between the FET and NC groups to examine the growth rate. Multiple regression analysis was performed to determine the relationship between birth size and baseline characteristics. RESULTS: The growth rate was higher in the first trimester in the FET group than in the NC group (difference: 0.19 mm/day, p = 0.018). CRL, EFW, and adjusted birthweight were higher in the FET group than in the NC group throughout pregnancy. The factors associated with the development of larger offspring through FET than through NC were advanced maternal age, primiparity, cesarean section delivery, and high birthweight. CONCLUSIONS: Throughout pregnancy, FET resulted in a larger offspring than in NC, with accelerated growth observed only during the first trimester. Thus, FET highly affects early fetal development.

Estimated Prevalence of Cronkhite-Canada Syndrome, Chronic Enteropathy Associated With SLCO2A1 Gene, and Intestinal Behçet's Disease in Japan in 2017: A Nationwide Survey.

BACKGROUND: Cronkhite-Canada syndrome (CCS), chronic enteropathy associated with SLCO2A1 gene (CEAS), and intestinal Behçet's disease (BD) are classified as intractable intestinal disorders in Japan. However, the national prevalence of these diseases remains unknown. We performed a nationwide survey to estimate the patient numbers and prevalence rates of these diseases throughout Japan in 2017. METHODS: We conducted a mail-based survey targeting hospitals across Japan to estimate the annual numbers of patients with CCS, CEAS, and intestinal BD in 2017. Using a stratified random sampling method, we selected 2,979 hospital departments and asked them to report the number of patients who met specific diagnostic criteria. The total number of patients for each disease was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. The corresponding prevalence rates per 1,000,000 population were calculated based on the mid-year population of Japan in 2017. RESULTS: The overall survey response rate was 68.1% (2,029 departments). The estimated numbers of patients with CCS, CEAS, and intestinal BD were 473 (95% confidence interval [CI], 357-589), 388 (95% CI, 289-486), and 3,139 (95% CI, 2,749-3,529), respectively; the prevalence rates per 1,000,000 population were 3.7 (male: 4.0; female: 3.5), 3.1 (male: 3.0; female: 3.1), and 24.8 (male: 24.5; female: 25.0), respectively. The male-to-female ratios were 1.10, 0.94, and 0.93 for patients with CCS, CEAS, and intestinal BD, respectively. CONCLUSIONS: Estimates of the national prevalence of CCS, CEAS, and intestinal BD in Japan were generated and found to be higher than those previously reported.

Predicting short-term life expectancy of patients with end-stage gastric cancer using Onodera's prognostic nutritional index.

BACKGROUND: Although the Onodera's prognosis nutritional index (O-PNI) has been used to predict long-term life expectancy, its use to predict life expectancy within 12 weeks has not been discussed. In this study, we examined the usefulness of the O-PNI to predict short-term life expectancy in patients with end-stage gastric cancer. METHODS: Blood samples from 425 patients who underwent surgery for gastric cancer at Toho University Omori Hospital from January 2001 to the end of December 2018 were analyzed. In 184 of 425 patients, a complete set of four blood sampling data were available at 12, 8, 4, and 1 week before death. The cutoff values and c-indices of O-PNI for predicting short-term life expectancy was calculated using the receiver operating characteristic curve. RESULTS: The shorter the life expectancy, the lower the O-PNI. For life expectancy of 8, 4, and 1 week, the optimal cutoff values for O-PNI were 40.4 (sensitivity 80.1%, specificity 44.6%); 38.3 (sensitivity 80.2%, specificity 54.1%); and 35.5 (sensitivity 80.4%, specificity 55.3%), respectively. CONCLUSIONS: In most patients, the O-PNI was below 40.4, 38.3, and 35.5 at 8, 4, and 1 week, respectively, before death, with 80% sensitivities. The O-PNI may be useful for predicting the short-term life expectancy in patients with end-stage gastric cancer.

Neoadjuvant Chemotherapy With Anthracycline-Based Regimen for BRCAness Tumors in Triple-Negative Breast Cancer.

BACKGROUND: A subgroup of triple-negative breast cancer (TNBC) shows impaired BRCA1 function owing to causes other than mutation, which is called "BRCAness." DNA-damaging agents are known to have more efficacy in BRCA1-mutant tumors than mitotic poisons. We conducted a prospective single-arm clinical trial of neoadjuvant chemotherapy (NAC) using an anthracycline-based regimen without taxanes for BRCAness TNBCs. MATERIALS AND METHODS: BRCAness was examined using the multiplex ligation-dependent probe amplification (MLPA) method in TNBC cases. For BRCAness cases, NAC was performed with anthracycline-based regimens without additional taxanes. RESULTS: A total of 30 patients with TNBC were enrolled. MLPA was successfully performed in 25 patients. Eighteen patients (72%) showed BRCAness. Twenty-three patients received NAC as per the protocol. On analysis, the clinical response rate (complete response plus partial response) was 76.4%, and the pathological complete response rate was 35.3%. CONCLUSIONS: The interim analysis revealed that the pathological complete response rate was lower than estimated. Therefore, BRCAness by MLPA was not sufficient to predict the therapeutic response to anthracycline-based regimens in TNBC.

Estimating nationwide cases of sexually transmitted diseases in 2015 from sentinel surveillance data in Japan.

BACKGROUND: The rates of newly diagnosed cases of sexually transmitted diseases, including genital chlamydial infection and gonorrhea, are important for prevention and control of these diseases. However, nationwide rates are not reported in Japan. METHODS: We used the number of cases of sexually transmitted diseases reported by nationwide sentinel surveillance in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions, drawn from the Survey of Medical Institutions of Japan. The number of cases of sexually transmitted diseases in the total population was estimated using the ratio estimation method with the number of all disease outpatients as auxiliary information. This method is currently used for estimating influenza cases from sentinel surveillance data in Japan. RESULTS: The estimated number of newly diagnosed cases per 100,000 population in 2015 in Japan was 244 (95% confidence interval 211-277) for genital chlamydial infection, 87 (95% confidence interval 74-100) for genital herpes, 61 (95% confidence interval 29-93) for condyloma acuminatum, and 89 (95% confidence interval 64-113) for gonorrhea. CONCLUSION: We estimated the nationwide number of newly diagnosed cases of sexually transmitted diseases in Japan from sentinel surveillance data. This provides useful information for public health policy-making.

Venous thromboembolism in cancer patients: report of baseline data from the multicentre, prospective Cancer-VTE Registry.

BACKGROUND: The Cancer-VTE Registry evaluates the occurrence and management of venous thromboembolism in Japanese participants with major solid tumors. Using Registry data, we evaluated the frequency of concurrent venous thromboembolism in cancer patients prior to treatment initiation by cancer type. METHODS: The Cancer-VTE Registry is an ongoing (March 2017-September 2020) prospective cohort study using a nationwide, multicentre clinical registry. Participants aged ≥20 years with colorectal, lung, stomach, pancreatic, breast or gynecologic cancer, confirmed staging, ≥6 months life expectancy post-registration and who had undergone venous thromboembolism screening were managed with routine clinical care. Venous thromboembolism frequency at registration was evaluated. RESULTS: Of 9735 participants, 571 (5.9%) had venous thromboembolism at baseline, including asymptomatic [5.5% (n = 540)] and symptomatic venous thromboembolism [0.3% (n = 31)]. Most participants with venous thromboembolism (n = 506, 5.2%) had deep vein thrombosis only; 65 (0.7%) had pulmonary embolism with/without deep vein thrombosis. The prevalence of distal and proximal deep vein thrombosis was 4.8% (n = 466) and 0.9% (n = 83), respectively. The highest prevalence of venous thromboembolism was for pancreatic cancer (8.5%) and the lowest for breast cancer (2.0%). Venous thromboembolism prevalence increased as cancer stage advanced. CONCLUSIONS: Although there was a marked difference in venous thromboembolism by cancer type, the data suggest that cancer stage is an important risk factor for venous thromboembolism. Thus, metastasis seems a critical risk factor for venous thromboembolism. This is the first demonstration of venous thromboembolism prevalence and risk factors in Japanese cancer patients prior to treatment. TRIAL REGISTRATION: UMIN000024942.

Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study).

BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

Efficacy and safety of insulin degludec U100 and insulin glargine U100 in combination with meal-time bolus insulin in hospitalized patients with type 2 diabetes: an open-label, randomized controlled study.

The short-term efficacy and safety of insulin degludec U100 (IDeg) in patients with type 2 diabetes have not been reported widely. We compared insulin IDeg and insulin glargine U100 (IGla) for glycemic control and glucose variability in hospitalized patients with type 2 diabetes. In an open-label, multicenter, randomized controlled trial, 74 patients were randomly assigned to either the IDeg (36 patients) or IGla (38 patients) group and were administered with basal-bolus therapy during hospitalization. Following the start of the treatment, on day 11, glucose variability was assessed by continuous glucose monitoring. A fasting blood glucose level of 110 mg/dL and 2-hour postprandial blood glucose level of 180 mg/dL throughout at least one day during the observation period were achieved in 31.3% (10/32) and 30.6% (11/36) of the patients in the IDeg and IGla groups, respectively. The 6-point self-monitoring of blood glucose profiles showed a significant difference between the two groups. On day 7, the intra-day variation was larger in the IDeg group than in the IGla group. The incidence of hypoglycemia or glucose variability was comparable in the two groups. This study suggests that short-term efficacy and safety of IDeg and IGla in patients with type 2 diabetes during the initial phase of basal-bolus therapy were comparable, and these results can help in deciding which treatment to opt for.

Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind, randomized controlled trial.

BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 µg/kg/h) or salbutamol (500 µg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.