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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.

Zinc is an essential micronutrient that promotes normal growth, development and immune function. In the context of persistent dietary zinc inadequacies, large-scale food fortification can help fill the gap between intake and requirements. Burkina Faso mandates wheat flour fortification with iron and folic acid. We used activity-based cost modelling to estimate the cost of adding zinc to the country's wheat flour fortification standard assuming (1) no change in compliance with the national standard, and (2) a substantial improvement in compliance. We used household food consumption data to model effective coverage, that is, the number of women of reproductive age (WRA) predicted to achieve adequate zinc density (zinc intake/1000 kcal) with the addition of fortification to diets. Without interventions, the prevalence of inadequate dietary zinc density was ~35.5%. With no change in compliance, the annual average incremental cost of adding zinc to fortified wheat flour was $10,347, which would effectively cover

Introduction Many adult cigarette smokers use electronic cigarettes (e-cigarettes) to cut down on or quit smoking cigarettes. E-cigarettes with higher abuse potential and appeal might facilitate complete switching. E-liquid nicotine concentration and flavor are two of the characteristics that may affect the abuse potential and appeal of e-cigarettes. The objective of this systematic review was to compile results from survey, animal, human laboratory, and clinical studies to understand the possible effects of nicotine concentration and flavor on abuse potential and appeal of e-cigarettes in adult current and former cigarette and e-cigarette users. Aims and Methods A comprehensive literature search was conducted in Ovid Medline and PsycINFO followed by citation tracking in Web of Science Core Collection. Peer-reviewed studies published in English between 2007 and August 2020 were selected that analyzed differences between e-liquid nicotine concentration and/or flavors, had outcome measures related to abuse potential and/or appeal, and included adult humans (18+) or animals. A total of 1624 studies were identified and screened. A qualitative synthesis of results was performed. Results Results from 104 studies included in this review suggest that higher nicotine concentration and access to a variety of flavors are likely to be associated with higher abuse potential and appeal of e-cigarettes for adult current and former cigarette and e-cigarette users. Conclusions Higher nicotine concentrations and the availability of a variety of flavors in e-cigarettes might facilitate complete substitution for cigarettes. Future e-cigarette regulations should take into account their impact on smokers, for whom e-cigarettes may be a cessation tool or reduced-harm alternative. Implications E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 μg/dL; 95% CI: 2.62–6.75; effectiveness, n = 13: 6.28 μg/dL; 95% CI: 5.03–7.77 μg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60–0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31–0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11–0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13–0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68–0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74–0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea., Zinc fortification increased plasma/serum zinc concentrations and reduced the prevalence of zinc deficiency; limited evidence indicated that MMN + zinc-fortified food increased body weight and reduced the incidence of fever and diarrhea.

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlappingmir-663correlated with maternal obesity, metabolic and immune markers, and infant behavior. ADUX4hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements ofDUX4cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.

ObjectivesLupron 11.25 mg has both a narrow indication and a high cost compared to other Lupron presentations. Prior to our study initiation there was no clear distinction between presentations when ordering within the health-system’s Electronic Health Record (EHR). This resulted in inappropriate product selection, payment and billing errors that negatively impact our healthcare system. To reinforce prior education efforts, a new approach was considered leveraging the EHR with information to steer prescribers to the proper Lupron presentation based on indication. This study aimed to reduce off-label prescribing for Lupron 11.25 mg (NDC 00074-3663-03) by 25% by 02/28/2022 without negatively impacting the insurance collection rate.MethodsBaseline Lupron 11.25 mg adult kit administrations one year prior to intervention and off-label prescribing was found to account for 22.7% of administrations. In December 2021 intervention order questions were added to Lupron 11.25 mg in the EHR. One and two-month data was obtained after implementing order questions within the EHR. Lupron 11.25 mg administrations were classified into one of four categories to determine impact on off-label prescribing.ResultsIn the one- and two-month post-implementation periods off-label prescribing was 0% and 15.3% respectively, a reduction of 22.7% to and 7.4% respectively from the baseline assessment. There were no clinical denials found in either post-implementation reporting period.ConclusionThis report adds to the body of evidence that leveraging the EHR can lead to healthcare savings and illustrates how patient and healthcare system burden can be reduced by prompting thought and direction when a medication has indication specific dose requirements.

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 ( 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.

Concern that synthetic food dyes may impact behavior in children prompted a review by the California Office of Environmental Health Hazard Assessment (OEHHA). OEHHA conducted a systematic review of the epidemiologic research on synthetic food dyes and neurobehavioral outcomes in children with or without identified behavioral disorders (particularly attention and activity). We also conducted a search of the animal toxicology literature to identify studies of neurobehavioral effects in laboratory animals exposed to synthetic food dyes. Finally, we conducted a hazard characterization of the potential neurobehavioral impacts of food dye consumption. We identified 27 clinical trials of children exposed to synthetic food dyes in this review, of which 25 were challenge studies. All studies used a cross-over design and most were double blinded and the cross-over design was randomized. Sixteen (64%) out of 25 challenge studies identified some evidence of a positive association, and in 13 (52%) the association was statistically significant. These studies support a relationship between food dye exposure and adverse behavioral outcomes in children. Animal toxicology literature provides additional support for effects on behavior. Together, the human clinical trials and animal toxicology literature support an association between synthetic food dyes and behavioral impacts in children. The current Food and Drug Administration (FDA) acceptable daily intakes are based on older studies that were not designed to assess the types of behavioral effects observed in children. For four dyes where adequate dose-response data from animal and human studies were available, comparisons of the effective doses in studies that measured behavioral or brain effects following exposure to synthetic food dyes indicate that the basis of the ADIs may not be adequate to protect neurobehavior in susceptible children. There is a need to re-evaluate exposure in children and for additional research to provide a more complete database for establishing ADIs protective of neurobehavioral effects.

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.

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. 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. 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. 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.

Primary healthcare (PHC) clinics are the point of access for many COVID-19 patients; however, the focus of crisis response work has been in securing hospital capacities. The purpose of this study was to describe the early nurse management experiences from PHC clinics within Greater Helsinki dedicated to caring for all ambulatory patients with possible COVID-19 symptoms. The study objectives were to make PHC crisis response contributions known and to provide an in-action review (IAR) of crisis response efforts. Nurse managers from the four COVID-19 hubs in Greater Helsinki were interviewed using thematic pair interviews. The data were analyzed inductively using thematic analysis, by which four main themes emerged: (1) capacity development led to a state of flux, (2) infection prevention control (IPC) was critical, (3) management of staff was essential in facilitating crisis response, and (4) respondents' personal experiences. The state of flux stressed the provision of PHC services, but quick developments in telemedicine eased that burden. Conversation surrounding IPC was extensive, though discrepancies suggest that global efforts to standardize IPC practices must begin locally. Leadership was adjusted to accommodate for the crisis, especially regarding the motivation of staff. A vision to aspire toward in crisis recovery is needed.

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.

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.

Low gestational weight gain (GWG) is a known risk factor of low birthweight. Although studies have previously examined the associations between GWG and birthweight, the period-specific effects of low GWG in each trimester remain unclear. This study aimed to quantify the trimester-specific direct effects of low GWG in Japanese women on birthweight. Using perinatal data from a cohort study, we analyzed pregnant women delivered at an obstetrics/gynecology hospital between October 2006 and May 2010. We focused on women with a pre-pregnancy body mass index (BMI) below 25 kg/m2. The exposure was low GWG. The gestation period was subdivided into trimesters, and the direct effects of low trimester-specific GWG on birthweight were estimated using marginal structural models. These models were guided by a direct acyclic graph that incorporated potential confounders, including pre-pregnancy BMI, age, smoking during pregnancy, height, and parity. We analyzed 563 women and their families. The mean cumulative GWG by the end of the first, second, and third trimesters was 0.9, 6.2, and 10.7 kg, respectively. Approximately 14.0% of the women gained total weight below the range recommended by Japanese Ministry of Health, Labour and Welfare. The direct effects of low GWG on birthweight were 65.9 g (95% confidence interval: 11.4, 120.5), −195.4 g (−263.4, −127.4), and −188.8 g (−292.0, −85.5) for the first, second, and third trimesters, respectively. Insufficient weight gain in the second and third trimesters had a negative impact on birthweight after adjusting for pre-pregnancy BMI and other covariates.

BACKGROUNDThe precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility.OBJECTIVE AND RATIONALEThis review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility.SEARCH METHODSRelevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis.OUTCOMESSpermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility.WIDER IMPLICATIONSA greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

This study investigated the association between maternal home blood pressure (HBP) trajectory during pregnancy and infant birth weight. A total of 755 pregnant women were included in this prospective cohort study. A group-based trajectory model identified six trajectory groups for home systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Next, the association of HBP trajectory groups with infant birth weight was evaluated using a general linear model considering potential confounding factors. For home SBP and MAP, the trajectory groups with a low-steep J-curve, moderate J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the low-J-curve group. Among the trajectory groups for home DBP, the moderate-steep J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the group with low-J-curve. The effect sizes of the trajectory groups varied in infant birth weight from -0.21 standard deviations (SDs) (95% confidence interval (CI): -0.42 to -0.01 SD) to -1.13 SD (95% CI: -1.54 to -0.72 SD). In the analyses of infant birth weight in grams, effect sizes that were significantly associated with infant birth weight varied from -84 g (95% CI: -167 to -1 g) to -567 g (95% CI: -732 to -402 g). Trajectory groups with a moderate-reverse J-curve for home SBP, DBP, and MAP were not significantly associated with infant birth weight. Maternal HBP trajectory during pregnancy was an indicator of infant birth weight. Further studies evaluating the associations between HBP during pregnancy and other perinatal outcomes are needed.

This N=173,426 social science dataset was collected through the collaborative COVIDiSTRESS Global Survey – an open science efort to improve understanding of the human experiences of the 2020 COVID-19 pandemic between 30th March and 30th May, 2020. The dataset allows a cross-cultural study of psychological and behavioural responses to the Coronavirus pandemic and associated government measures like cancellation of public functions and stay at home orders implemented in many countries. The dataset contains demographic background variables as well as measures of Asian Disease Problem, perceived stress (PSS-10), availability of social provisions (SPS-10), trust in various authorities, trust in governmental measures to contain the virus (OECD trust), personality traits (BFF-15), information behaviours, agreement with the level of government intervention, and compliance with preventive measures, along with a rich pool of exploratory variables and written experiences. A global consortium from 39 countries and regions worked together to build and translate a survey with variables of shared interests, and recruited participants in 47 languages and dialects. Raw plus cleaned data and dynamic visualizations are available., Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) JP17H00875 JP18K12015 JP20H04581 JP20K14222, Grant Agency of the Czech Republic GC19-09265J, Consejo Nacional de Ciencia y Tecnologia (CONACyT) CVU: 613905, FWO, HSE University Basic Research Program

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost‐effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low‐ and middle‐income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy‐three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC., The specific aim of this research prioritization exercise was to inform the direction of research and investments needed to support the implementation of multiple micronutrient supplementation (MMS) interventions for pregnant women in low‐ and middle‐income countries (LMIC) using the Child Health and Nutrition Research Initiative methodology. This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

Background It is important to determine whether anthracycline-containing regimens or taxane-containing regimens are more effective in individual patients. The present study compared the efficacy of six cycles of docetaxel and cyclophosphamide (TC6) with that of three cycles of 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel (FEC-D) in Japanese patients with hormone receptor (HR)-negative breast cancer (BC) to identify subtypes requiring anthracycline treatment. Methods The study included 103 patients with operable HR-negative BC. Of these patients 53 received FEC-D and 50 received TC6. The primary endpoint was pathological complete response (pCR). The secondary endpoints were safety, breast-conserving surgery, disease-free survival (DFS) and overall survival (OS). The predictive factors for each regimen were evaluated. Results Of the 103 patients, 97 completed the study (FEC-D, 50 patients; TC6, 47 patients). The pCR rate was higher with FEC-D (36%) than with TC6 (25.5%); however, the difference was not significant (P = 0.265). TC6 was safer than FEC-D, as the adverse events with docetaxel in the FEC-D regimen were similar to those with the TC6 regimen. Among patients with basal BC, the pCR rate was significantly higher with FEC-D (42.9%) than with TC6 (13.6%; P = 0.033). Among patients with triple-negative breast cancer (TNBC), the DFS and OS were significantly better with FEC-D than with TC6 (P = 0.016 and P = 0.034, respectively). Conclusion TC6 was not as effective as FEC-D for treating HR-negative BC, as TC6 was not sufficient to treat TNBC, particularly the basal subtype. Our findings suggest that anthracyclines are better treatment options than taxanes for basal BC.

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.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.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.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.

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support.

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.

Although many publications have reported the incidence of venous thromboembolism (VTE) in patients with cancer from Western countries, to date, no prospective East Asian studies have been published, and potential racial differences remain unclear. The multicenter, prospective, observational Cancer-VTE Registry aimed to clarify the incidence of VTE and bleeding and identify risk factors in Japanese patients with solid tumors after one year of follow-up.Patients with colorectal, lung, stomach, pancreatic, breast, or gynecologic cancer were enrolled after VTE screening and before starting cancer treatment. The follow-up period was one year. The main outcomes were the incidences of symptomatic VTE, bleeding events (major or clinically relevant non-major), and all-cause death, evaluated according to VTE presence/absence at baseline. Multivariate analyses were conducted to identify risk factors for events.Among 9630 patients, the one-year cumulative incidences of symptomatic VTE, bleeding events, and all-cause death were 0.5%, 1.4%, and 12.2%, respectively. The majority of VTEs identified at baseline were asymptomatic distal deep vein thromboses; however, affected patients had higher event rates during the follow-up period. The most important independent risk factor for developing symptomatic VTE, bleeding events, and death during the follow-up period was the presence of symptomatic or asymptomatic VTE at baseline.These data have revealed the incidence of symptomatic VTE in Japanese patients with solid tumors during one year of follow-up. The presence of any VTE before initiating cancer treatment was an independent risk factor for symptomatic VTE, bleeding events, and death during subsequent treatment.

ObjectiveTo clarify the impact of Japan’s Clinical Trials Act (CTA), which was enacted in April 2018, on subsequent clinical trial activity through an analysis of Japanese registry data.DesignRetrospective database study.SettingWe extracted information on clinical intervention studies registered between 1 April 2018 and 30 September 2020 in the conventional University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) and the new Japan Registry of Clinical Trials (jRCT). We collected and analysed information on registration dates, intervention types, funding, secondary sponsors and use of designated staff in multidisciplinary roles (research planning support, research administration, data management, statistical analysis, monitoring and auditing). The temporal trends in clinical trial activity after CTA enactment were examined.ResultsA total of 577 CTA-compliant specified clinical trials (ie, studies funded by pharmaceutical companies or studies evaluating the efficacy and safety of off-label drugs or devices in humans) were registered in the jRCT. During the same period, 5068 clinical trials were registered in the UMIN-CTR. The number of specific clinical trials increased immediately after the implementation of the CTA and stabilised in late 2019, whereas the number of clinical trials registered in the UMIN-CTR generally declined over time. Specified clinical trials that received industry funding and public grants were more likely to use designated staff in multidisciplinary roles.ConclusionsThe implementation of the CTA has not reduced the number of specified clinical trials, but has reduced the total number of intervention trials. The use of designated staff in multidisciplinary roles is associated with funding, secondary sponsors and multicentre studies. It was inferred that funding was needed to establish research infrastructure systems that support high-quality research.

Background Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1–7 lead to Dent disease-2, whereas those in exons 8–24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms. Methods Messenger RNA samples extracted from cultured urine-derived cells from a healthy control and a Dent disease-2 patient were examined to detect the 5′ end of the OCRL isoform. For protein expression and functional analysis, vectors containing the full-length OCRL transcripts, the isoform transcripts and transcripts with truncating mutations detected in Lowe syndrome and Dent disease-2 patients were transfected into HeLa cells. Results We successfully cloned the novel isoform transcripts from OCRL exons 6–24, including the translation-initiation codons present in exon 8. In vitro protein-expression analysis detected proteins of two different sizes (105 and 80 kDa) translated from full-length OCRL, whereas only one protein (80 kDa) was found from the isoform and Dent disease-2 variants. No protein expression was observed for the Lowe syndrome variants. The isoform enzyme activity was equivalent to that of full-length OCRL; the Dent disease-2 variants retained >50% enzyme activity, whereas the Lowe syndrome variants retained Conclusions We elucidated the molecular mechanism underlying the two different phenotypes in OCRL-related diseases; the functional OCRL isoform translated starting at exon 8 was associated with this mechanism.

Adequate zinc nutrition is important for child growth, neurodevelopment, immune function, and normal pregnancy outcomes. Seventeen percent of the global population is estimated to be at risk for inadequate zinc intake. However, zinc is not included in the fortification standards of several low- and middle-income countries with mandatory fortification programs, despite data suggesting a zinc deficiency public health problem. To guide policy decisions, we investigated the factors enabling and impeding the inclusion of zinc as a fortificant by conducting in-depth interviews with 17 key informants from 10 countries. Findings revealed the decision to include zinc was influenced by guidance from international development partners and enabled by the assessment of zinc deficiency, mandatory regional food fortification standards which included zinc, the World Health Organization (WHO) guidelines for zinc fortification, and the low cost of zinc compound commonly used. Barriers included the absence of zinc from regional fortification standards, limited available data on the efficacy and effectiveness of zinc fortification, and the absence of national objectives related to the prevention of zinc deficiency. To promote zinc fortification there is a need to put the prevention of zinc deficiency higher on the international nutrition agenda and to promote large-scale food fortification as a key deficiency mitigation strategy.

Almost a quarter century has passed since the first nationwide survey on ulcerative colitis (UC) and Crohn’s disease (CD) was conducted in Japan. In this study, we used a nationwide survey to estimate the number of patients and prevalence of these diseases in Japan in 2014. We conducted a mail-based survey targeting hospitals to estimate the annual numbers of patients with UC and CD in 2014. Respondents were asked to report the numbers of patients who met specific diagnostic criteria for these two conditions. A stratified random sampling method was used, and a total of 3712 departments (internal medicine, surgery, pediatrics, and pediatric surgery) were selected for analysis. The overall and sex-specific annual numbers of UC and CD patients were estimated. The corresponding prevalence rates per 100,000 population were calculated by dividing the number of patients with each disease by the mid-year population of Japan in 2014. The overall survey response rate was 56.7% (2016 departments). The estimated numbers of patients with UC and CD were 219,685 (95% confidence interval: 183,968–255,403) and 70,700 (56,702–84,699), respectively. The annual prevalence rates of UC and CD per 100,000 population were 172.9 (men: 192.3; women: 154.5) and 55.6 (men: 79.5; women: 33.1), respectively. These numbers are almost tenfold increase in comparing the previous survey (22,300 in UC and 7,400 in CD). The male-to-female ratios were 1.24 for UC and 2.40 for CD, and the UC-to-CD ratio was 3.11. The prevalence of UC and CD in Japan has risen substantially over the past two decades, and their disease burden requires further examination.

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

Background Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies. Methods We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype. Results We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered. Conclusions Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774

Background: Low fertility persists but remains unexplained in Japan. We examined whether the probability of pregnancy was influenced by coital frequency, age, reproductive age (assessed by antim&uuml, llerian hormone, AMH), and BMI. Methods: We established a two-year prospective study with a sample of hormonally monitored Japanese women aged 23&ndash, 34 years wanting to conceive their first child. For a maximum of 24 weeks participants recorded menstrual bleeding, sexual intercourse, ovulation, and pregnancy. Additional information on pregnancy and infertility treatment was collected one and two years after intake. Results: The natural conception rate and coital frequency were both low in this sample. Among 80 participants, 44% (35) naturally conceived in 24 weeks. After two years, 74% (59) of women had delivered or were currently pregnant, 50% (40) due to natural and 24% (19) due to assisted conception, and 5% (4) were lost to follow-up. By two years, 56% (45) of women had sought fertility treatment. In 18% (58/319) of the observed ovarian cycles across 24 weeks there was no intercourse in a fertile period. Higher coital frequency at intake was associated with increased probability of conception by 24 weeks of follow-up (OR 1.23, 95%CI 1.02, 1.47). Chronological age, reproductive age, and BMI were not associated with the probability of pregnancy at 24 weeks. Conclusions: Our results suggest that first, natural conception rates could potentially increase with more frequent and well timed intercourse, and second that further work is needed to understand why even in a motivated sample of women monitoring their fertile periods, both the conception and coitus rates were low.

Background Pathological complete response (pCR) is often achieved by neoadjuvant chemotherapy (NAC), particularly in hormone receptor-negative breast cancer. Contrast-enhanced magnetic resonance imaging (cMRI) is the most reliable imaging modality to evaluate the pathological effect of NAC. Ultrasonography is indispensable to collect representative specimens from the target lesion by core needle biopsy (CNB). This study aimed to evaluate the accuracy of predicting pCR by adding CNB after NAC, in cases with complete clinical response (cCR) diagnosed by cMRI. Methods In this prospective multicentre study, we evaluated patients diagnosed with cCR by cMRI after NAC. Ultrasound-guided CNB (uCNB) using a 14G needle was performed without clip markers under general anaesthesia as planned surgery. Specimens collected by uCNB were compared to those resected surgically and were categorized as (i) no carcinoma (ypT0), (ii) no invasive carcinoma and only residual carcinoma in situ (ypTis) and (iii) residual invasive carcinoma. The concordance of pathological results between the uCNB and surgical specimens was evaluated. Results Of the 83 patients evaluated, 41 (49.4%) and 17 (20.5%) of them had ypT0 and ypTis, respectively. The false negative rates (FNR), sensitivity and specificity for predicting ypT0 by uCNB were 50.0%, 50.0%, 100%, respectively, and those for predicting ypT0+ypTis were 28.0%, 72.0% and 98.3%, respectively. The concordance rates were 74.7% (62/83) for ypT0 and 90.4% (75/83) for ypT0+ypTis. Conclusion In cCR cases diagnosed by cMRI, uCNB was not accurate enough to predict pCR. Additional modalities like clip placements and/or thicker core needles may be required for better prediction.

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.

Background: Human milk vitamin B12 (B12) concentrations depend on maternal status and intake; only few data are available in high-income countries. Objective: We assessed human milk B12 concentrations during the first 6 months postpartum in Norwegian women and its association with maternal dietary B12 intake and maternal urinary methylmalonic acid (MMA) concentration. Methods: In this cross-sectional study, 175 mothers, exclusively (80%) or partially (20%) breastfeeding, were included. Milk B12 was measured by IMMULITE®/IMMULITE® 1000 B12 competitive protein binding assay and urinary MMA relative to creatinine (MMA/Cr) by liquid chromatography-tandem-mass spectrometry. Maternal habitual B12 intake and supplement use were estimated using a food frequency questionnaire. Results: Mean human milk B12 concentration was 327 pmol/L (range 140-1089), with 402 pmol/L at 1 month (n = 21), 333 pmol/L at four months (n = 32), and 299 pmol/L at 6 months (n = 21). Maternal B12 intake was 5 µg/d, 89% met the Estimated Average Requirement, and supplement use did not affect milk B12 concentrations. MMA/Cr was low in all women compared with published data. In exclusively breastfeeding women, MMA/Cr (beta (95% CI) -42.5 (-82.5, -2.5) and time since birth (-4.9 (-9.6, -0.3)) were significant predictors of human milk B12 concentrations. There was no association between total B12 intake and milk B12 concentration or between total B12 intake and MMA/Cr. Conclusions: Maternal B12 status and human milk B12 concentrations are likely sufficient, based on adequate maternal B12 dietary intake combined with low urinary MMA concentrations. Nevertheless, milk B12 concentration fell during 6 months postpartum while maternal B12 status did not change. This study was funded by Oslo Metropolitan University.

Author(s): Sato, Kei; Mori, Ryutaro; Hiroshima, Yukihiko; Oba, Mari S; Matsuyama, Ryusei; Bouvet, Michael; Hoffman, Robert M; Endo, Itaru | Abstract: BACKGROUND:Peritoneal recurrence of pancreatic cancer is a frequent and lethal outcome after R0 resection. A method to predict peritoneal recurrence could be helpful in its prevention. MATERIALS AND METHODS:Peritoneal washings were prospectively obtained from 29 patients in whom R0 resection was performed. Cytological examination (CY) and real-time reverse transcription polymerase chain reaction (RT-PCR) of the peritoneal washing for the detection of cancer-related genes, CEACAM5, KRT7, KRAS, and MUC1, were performed. Clinicopathological characteristics and real-time RT-PCR results of the peritoneal washing were compared between patients whose pancreatic cancer recurred peritoneally (nn=n7) and those patients who it did not recur (nn=n22). RESULTS:Only one CY-positive (CY+) case was detected, and that patient recurred. MUC1 mRNA expression was significantly higher in the recurrence group (Pn=n0.015). Cumulative incidence-function analysis demonstrated that peritoneal recurrence rate was significantly higher in MUC1-positive (MUC1+) patients (Pn=n0.044). MUC1+ patients had significantly decreased disease-free survival (Pn=n0.009) and disease-specific survival (Pn=n0.031). MUC1 protein was detected in the primary tumor in 18 of 29 patients. However, no significant difference was observed in the expression of MUC1 protein in peritoneal washings from the primary tumor (Pn=n0.579). CONCLUSIONS:High expression of MUC1 mRNA in peritoneal washings is a significant risk factor for peritoneal recurrence of pancreatic cancer after R0 resection along with poor disease-specific survival. RT-PCR of MUC1 mRNA in peritoneal washing may be useful for individualization of adjuvant chemotherapy.

Background Dasatinib has shown promising anti-leukemic activity against chronic myeloid leukemia (CML). However, patients receiving dasatinib frequently require dose reductions and treatment interruptions (treatment alteration). Methods We prospectively analyzed the frequency and significance of treatment alteration during dasatinib therapy in patients with CML. In all patients, trough plasma concentrations of dasatinib (Cmin) at steady state were assessed on day 28 of therapy. Results 28% of patients had their doses reduced at a median of 42 days, and 25% of patients had temporarily interrupted at a median of 54 days after treatment initiation. The overall dasatinib treatment alteration-free rate at 1 year was 66%. Age was significantly correlated with Cmin on day 28 (p = 0.014), and the correlation remained significant after adjusting dasatinib dose (g), body weight (kg) (Cmin/D/W) (p = 0.026). In the univariate analysis, deep molecular response, advanced PS, higher Cmin/D/W were associated with a significantly higher risk of treatment alteration (HR 4.19, 95% CI: 1.06–16.60, p = 0.041; HR 5.26, 95% CI: 1.33–20.80, p = 0.018; and HR 10.15, 95% CI: 2.55–40.48, p = 0.001, respectively). In the multivariate analysis, advanced PS and higher Cmin/D/W were correlated with the incidence of treatment alteration (HR 4.78, 95% CI: 1.01–22.70, p = 0.049; HR 6.17, 95% CI: 1.17–32.50, respectively). Conclusion Current data demonstrate that patients treated with dasatinib who displayed a high Cmin/D/W value and/or advanced PS were at a high risk for altered treatment.

Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.

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.

ObjectivesThe 23-valent pneumococcal polysaccharide vaccine (PPSV23) was included in Japan’s national immunisation programme for older adults in 2014. While vaccination coverage has increased following the implementation of the national immunisation programme, little is known about the factors that have influenced changes in PPSV23 uptake in Japan. This study aimed to investigate the effects of municipality-level activities implemented to improve vaccine uptake during the fiscal year 2015 (April 2015–March 2016).DesignCommunity-based national survey. A postal and web-based nationwide survey was sent to all municipalities in Japan in June 2016 (n=1741). The survey included questions regarding PPSV23 coverage, out-of-pocket costs by individuals for vaccination and community-level activities implemented to improve and promote PPSV23 uptake. Municipality-level and prefecture-level variables (eg, unemployment rates, average per capita income) retrieved from published sources were also incorporated to explore the impact of social determinants on vaccine uptake.SettingJapan.ParticipantsMunicipal vaccination officers.Primary and secondary outcome measuresThe primary study outcome was PPSV23 coverage among adults aged 65 years in Japanese municipalities.ResultsA total of 1010 municipalities (58.0%) responded to the survey. The median PPSV23 coverage among responding municipalities was 41.8%. Vaccine coverage increased by 18.7% (16.7%–20.7%)%) in municipalities that sent a direct mail notification to the target population of adults compared with municipalities that did not send any notification. Vaccine coverage decreased by 3.02% (2.4%–3.6%)%) for every 1000 JPY increase in out-of-pocket costs. Municipality-level unemployment rates and average per capita income were negatively associated with PPSV23 coverage.ConclusionsThis nationwide survey provides insight into factors that may influence PPSV23 coverage in Japanese municipalities. Reduced out-of-pocket costs and direct mail notifications to the target population were associated with higher PPSV23 coverage in Japanese municipalities.