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The peptide mimetic, NC114, is a promising anticancer compound that specifically kills colorectal cancer cells without affecting normal colon epithelial cells. In our previous study, we observed that NC114 inhibited the Wnt/β‐catenin pathway, with significant downregulation of both Ser 675‐phosphorylated β‐catenin and its target genes, cyclin D1 and survivin. However, the molecular mechanism responsible for its cytotoxic effect has not yet been fully characterized. In the present study, we demonstrated that NC114 prevented cell cycle progression from S to G2/M phase by downregulating cell cycle‐related gene expression, and also induced growth arrest in SW480 and HCT‐116 colorectal cancer cells. A novel covariation network analysis combined with transcriptome analysis revealed a series of signaling cascades affected by NC114 treatment, and identified protein kinase C‐δ (PKCδ) and forkhead box protein M1 (FOXM1) as important regulatory factors for NC114‐induced growth arrest. NC114 treatment inhibits the activation of PKCδ and its kinase activity, which suppresses MEK/ERK signaling. Attenuated MEK/ERK signaling then results in a reduction in FOXM1 phosphorylation and subsequent nuclear translocation of FOXM1 and β‐catenin. Consequently, formation of a T‐cell factor‐4 (TCF4)/β‐catenin transcription complex in the nucleus is inhibited and transcription of its target genes, such as cell cycle‐related genes, is downregulated. The efficacy of NC114 on tumor growth was confirmed in a xenograft model. Collectively, elucidation of the mechanism by which NC114 induces growth arrest in colorectal cancer cells should provide a novel therapeutic strategy for colorectal cancer treatment.

Heart fibrosis involves a feedback loop where stiffening increases fibrosis-related gene expression in myofibroblasts. Here authors reveal the mechanosensitive nuclear translocation of VGLL3, where it phase separates and promotes collagen production, and show that its knock-out is protective after myocardial infarction.

We describe a patient with bilateral cystic tumors of the pelvis. The left one rapidly grew during pregnancy and combined with the right one, whose clinical course made diagnosis difficult. A pregnant woman with a history of laparotomy was referred to us due to suspected bilateral pelvic cysts. The left-sided cyst had rapidly grown to 27 cm in diameter and merged with the right cyst, forming a large cyst occupying the entire pelvic cavity in the third trimester. Considering this rapid growth, cesarean section and resection of the cyst were performed at 37th week. The resected cyst consisted of two components: a large unilocular cyst containing serous fluid and a multilocular cyst suggestive of ovarian mucinous cystadenoma in the right ovary. The wall of the former largely lacked lining epithelium, but it was partly continuous with the latter mucinous epithelium. Immunohistochemically, estrogen and progesterone receptors were focally positive in the cyst wall, suggesting that pregnancy-associated sex-hormones may have contributed to the rapid growth of the cyst. We diagnosed this condition as a peritoneal inclusion cyst margining with a right ovarian mucinous cystadenoma. Peritoneal inclusion cyst should be considered in the differential diagnosis of a rapidly growing pelvic mass during pregnancy.

We experienced the giant seminoma with 18 × 10 × 10 cm sized and about 2.6 kg weight of 25 year old patient. We intensively examined the histological tissue type distributions in this giant seminoma. Most of the tumor consisted of seminoma components. In addition, the tumor included the very small fragments of yolk sac tumor and embryonal carcinoma component at the root part of the seminoma mass. This shows that intensive histological examination may contribute to the finding of other embryonic component of the large seminoma. This may show that leaving the seminoma growing may generate the other embryonic tumor component, not always big enough to find out in a routine procedure, during the growth, in the different way from the original mixed cell germ tumor.

Apical neural progenitors (aNPs) drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600) in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

p600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development.

Abstract Background Ventilator-associated pneumonia (VAP) is a challenging nosocomial problem in low- and middle-income countries (LMICs) that face barriers to healthcare delivery and resource availability. This study aimed to examine the incidence and predictors of VAP in Egypt as an example of an LMIC while considering death as a competing event. Methods The study included patients aged ≥ 18 years who underwent mechanical ventilation (MV) in an intensive care unit (ICU) at a tertiary care, university hospital in Egypt between May 2020 and January 2023. We excluded patients who died or were transferred from the ICU within 48 h of admission. We determined the VAP incidence based on clinical suspicion, radiological findings, and positive lower respiratory tract microbiological cultures. The multivariate Fine-Gray subdistribution hazard model was used to examine the predictors of VAP while considering death as a competing event. Results Overall, 315 patients were included in this analysis. Sixty-two patients (19.7%) developed VAP (17.1 per 1000 ventilator days). The Fine-Gray subdistribution hazard model, after adjustment for potential confounders, revealed that emergency surgery (subdistribution hazard ratio [SHR]: 2.11, 95% confidence interval [CI]: 1.25–3.56), reintubation (SHR: 3.74, 95% CI: 2.23–6.28), blood transfusion (SHR: 2.23, 95% CI: 1.32–3.75), and increased duration of MV (SHR: 1.04, 95% CI: 1.03–1.06) were independent risk factors for VAP development. However, the new use of corticosteroids was not associated with VAP development (SHR: 0.94, 95% CI: 0.56–1.57). Klebsiella pneumoniae was the most common causative microorganism, followed by Pseudomonas aeruginosa. Conclusion The incidence of VAP in Egypt was high, even in the ICU at a university hospital. Emergency surgery, reintubation, blood transfusion, and increased duration of MV were independently associated with VAP. Robust antimicrobial stewardship and infection control strategies are urgently needed in Egypt.

IntroductionCleft lip and/or palate (CL/P), the most prevalent congenital anomaly, has been associated with higher rates of child maltreatment. In particular, the presence of cleft lip has more of an impact on external appearance and may increase the risks of negative health outcomes such as parental postpartum depression; however, this concept remains controversial. Item #10 of the Edinburgh Postpartum Depression Scale is the assessment of parental self-harm ideation, and its presence in postpartum mothers merits risk assessments as an emergent issue that may affect the health of both mothers and infants. This study focused on the impact of CL/P on maternal self-harm ideation.MethodsOf 100,300 live births from a nationwide birth cohort in Japan, 238 mothers of infants with CL/P [186 children born with cleft lip (CL ± P) and 52 born with isolated cleft palate (CP)] were included in the analyses. The prospective association of children with CL/P and maternal self-harm ideation, which were acquired using item #10 in the Edinburgh Postpartum Depression Scale at 1 and 6 months postpartum, was examined using binomial logistic regression analyses after multiple imputations and with adjustments for several maternal (age at delivery, smoking habit, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables.ResultsThe prevalence of self-harm ideation in 238 mothers of infants with CL/P at 1 and 6 months were 14.7% (35/238) and 18.8% (45/238) [8.2% (8,185/100,062) and 12.9% (12,875/100,062) in the control group], respectively. The odds ratio (95% confidence interval) for maternal self-harm ideation increased with CL/P prevalence [1.80 (1.22–2.65) and 1.47 (0.98–2.18)] at 1 and 6 months of age, respectively. After stratified by the prevalence of cleft lip, we found significant differences in the CL ± P group but not in the CP group. Furthermore, persistent self-harming ideation was associated with a higher risk in the CL ± P group [2.36 (1.43–3.89)].ConclusionCL/P, particularly cleft lip, which is more noticeable externally, was associated with an increased prevalence of maternal self-harm ideation. The findings in this study indicate some potential benefits of increasing support for mothers who have infants with CL/P.

Objectives To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study.Design This study was a prospective birth cohort study.Setting This study population included 104 059 fetal records who participated in The Japan Environment and Children’s Study from 2011 to 2014.Participants Pregnant women whose children had undergone developmental testing were included in this analysis.Primary and secondary outcome measures Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development.Results Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers.Conclusion An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world.

Background: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. Methods: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. Results: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-

Objectives: Smoking is a significant risk factor for gingivitis and has detrimental effects on both oral health and the cardiovascular system. This study aimed to evaluate the association between cardiovascular biomarkers and gingival bleeding among smokers. Materials and Methods: This cross-sectional study comprising 60 smokers (mean age, 59.9±13.7 years) was conducted at an outpatient smoking cessation clinic. The smokers were divided into two groups based on the presence or absence of gingival bleeding, which was assessed by probing. α1-antitrypsin low-density lipoprotein complex (AT-LDL), an oxidatively modified LDL complex, causes progressive atherosclerosis. The clinical characteristics and blood markers including AT-LDL levels were measured in these patients. Results: Significantly higher (p=0.03) levels of AT-LDL, an oxidized LDL complex that promotes atherosclerosis, were observed among smokers with no gingival bleeding on probing when compared to that among smokers with gingival bleeding. The pocket depths in smokers without gingival bleeding were significantly (p=0.04) lower than those among smokers with gingival bleeding. Conclusion: The absence of gingival bleeding among smokers was associated with higher levels of AT-LDL. These findings could indicate reduced blood flow due to atherosclerosis among smokers with no gingival bleeding.

Abstract Background Although the Philippines targets malaria elimination by 2030, it remains to be a disease that causes considerable morbidity in provinces that report malaria. Pregnant women residing in endemic areas are a vulnerable population, because in addition to the risk of developing severe malaria, their pregnancy is not followed through, and the outcome of their pregnancy is unknown. This study determined the utility of real-world data integrated with disease surveillance data set as real-world evidence of pregnancy and delivery outcomes in areas endemic for malaria in the Philippines. Methods For the period of 2015 to 2019, electronic data sets of malaria surveillance data and Ospital ng Palawan hospital admission log of pregnant women residing in the four selected barangays of Rizal, Palawan were merged using probabilistic linkage. The source data for record linkage were first and last names, birth date, and address as the mutual variable. The data used for characteristics of the pregnant women from the hospital data set were admission date, discharge date, admitting and final diagnosis and body weight on admission. From the malaria surveillance data these were date of consultation, and malaria parasite species. The Levenshtein distance formula was used for a fuzzy string-matching algorithm. Chi-square test, and Mann–Whitney U test were used to compare the means of the two data sets. Results The prevalence of pregnant women admitted to the tertiary referral hospital, Ospital ng Palawan, was estimated to be 8.34/100 overall, and 11.64/100 from the four study barangays; that of malaria during pregnancy patients was 3.45/100 and 2.64/100, respectively. There was only one true-positive matched case from 238 women from the hospital and 54 women from the surveillance data sets. The overall Levenshstein score was 97.7; for non-matched cases, the mean overall score was 36.6 (35.6–37.7). The matched case was a minor who was hospitalized for severe malaria. The outcome of her pregnancy was detected from neither data set but from village-based records. Conclusions This proof-of-concept study demonstrated that probabilistic record linkage could match real-world data in the Philippines with further validation required. The study underscored the need for more integrated and comprehensive database to monitor disease intervention impact on pregnancy and its outcome in the Philippines.

BackgroundDuring the COVID-19 pandemic, much misinformation and disinformation emerged and spread rapidly via the internet, posing a severe public health challenge. While the need for eHealth literacy (eHL) has been emphasized, few studies have compared the difficulties involved in seeking and using COVID-19 information between adult internet users with low or high eHL. ObjectiveThis study examines the association between eHL and web-based health information–seeking behaviors among adult Japanese internet users. Moreover, this study qualitatively shed light on the difficulties encountered in seeking and using this information and examined its relationship with eHL. MethodsThis cross-sectional internet-based survey (October 2021) collected data from 6000 adult internet users who were equally divided into sample groups by gender, age, and income. We used the Japanese version of the eHL Scale (eHEALS). We also used a Digital Health Literacy Instrument (DHLI) adapted to the COVID-19 pandemic to assess eHL after we translated it to Japanese. Web-based health information–seeking behaviors were assessed by using a 10-item list of web sources and evaluating 10 topics participants searched for regarding COVID-19. Sociodemographic and other factors (eg, health-related behavior) were selected as covariates. Furthermore, we qualitatively explored the difficulties in information seeking and using. The descriptive contents of the responses regarding difficulties in seeking and using COVID-19 information were analyzed using an inductive qualitative content analysis approach. ResultsParticipants with high eHEALS and DHLI scores on information searching, adding self-generated information, evaluating reliability, determining relevance, and operational skills were more likely to use all web sources of information about COVID-19 than those with low scores. However, there were negative associations between navigation skills and privacy protection scores when using several information sources, such as YouTube (Google LLC), to search for COVID-19 information. While half of the participants reported no difficulty seeking and using COVID-19 information, participants who reported any difficulties, including information discernment, incomprehensible information, information overload, and disinformation, had lower DHLI score. Participants expressed significant concerns regarding “information quality and credibility,” “abundance and shortage of relevant information,” “public trust and skepticism,” and “credibility of COVID-19–related information.” Additionally, they disclosed more specific concerns, including “privacy and security concerns,” “information retrieval challenges,” “anxieties and panic,” and “movement restriction.” ConclusionsAlthough Japanese internet users with higher eHEALS and total DHLI scores were more actively using various web sources for COVID-19 information, those with high navigation skills and privacy protection used web-based information about COVID-19 cautiously compared with those with lower proficiency. The study also highlighted an increased need for information discernment when using social networking sites in the “Health 2.0” era. The identified categories and themes from the qualitative content analysis, such as “information quality and credibility,” suggest a framework for addressing the myriad challenges anticipated in future infodemics.

Objective The primary objective of this study was to investigate the parenting attitudes towards children with autism spectrum disorders in early childhood in Japan.Design This study was a cohort study. The participants were enrolled from January 2011 to March 2014. We obtained the prevalence of autism spectrum disorders at 3 years of age, parenting attitudes and other factors from questionnaires. We divided the participants into two groups, an autism spectrum disorders group and a non-autism spectrum disorders group, and compared the parenting attitudes.Setting This study used data from a Japanese birth cohort study: the Japan Environment and Children’s Study, conducted across 15 regional centres in Japan.Participants The full dataset of the Japan Environment and Children’s Study comprised 104 059 records. We excluded 17 889 records because the answer for the autism spectrum disorders in the questionnaire was blank. As a result, we analysed the remaining 82 411 mother–child pairs.Main outcome measures The primary outcome variable was parenting attitudes at 3.5 years of age, which was assessed using a questionnaire. We asked respondents 16 questions related to parenting attitudes, and they answered based on their behaviours. The independent variable was the prevalence of autism spectrum disorders at 3 years of age.Results Of the 82 411 participants, the children with autism spectrum disorders at 3 years of age were 372 (0.45%). In most questions about parenting attitudes, the autism spectrum disorders group had unfavourable responses. The difference was particularly noticeable when the parents taught their children social discipline. Unfavourable parenting attitudes were 16.6% in the autism spectrum disorders group and 0.8% in the non-autism spectrum disorders group in the question item with the largest difference between the two groups, a significant difference.Conclusions Parents of children with autism spectrum disorders tended to have unfavourable attitudes, suggesting the importance of parental training.

Background During the COVID-19 pandemic, numerous issues regarding end-of-life care for COVID-19 patients have been discussed. Among these issues, challenges related to the use of body bags following the death of COVID-19 patients have been suggested. This study aimed to identify the challenges faced by healthcare professionals (HCPs) when using body bags after the death of patients infected with COVID-19 in medical settings.Methods We conducted a qualitative descriptive study with semistructured in-depth interviews using inductive thematic analysis. From August to December 2021, we interviewed nurses and doctors who provided end-of-life care to COVID-19 patients focusing on their experiences with the use of body bags for the deceased.Results Of the 25 interviewees who mentioned body bag use, 14 were nurses (56%) and 13 were women (52%). The mean interview length was 52.0 min (SD 9.6 min). Challenges associated with body bag use were classified into four themes with eight categories: preserving the dignity of the deceased, consideration for the bereaved saying a final goodbye to a loved one in a body bag, the physical and emotional impact on HCPs, and diverse opinions on body bag use.Conclusion Our findings include ethical concerns about the dignity of the deceased, empathy for the grief of bereaved families, and the emotional and physical distress experienced by HCPs struggling with the recommendation to use body bags based on limited evidence. The diverse perspectives of HCPs in this study highlight potential issues that developers should consider when formulating more appropriate and acceptable guidelines/guidance and policies.

Objectives To evaluate the association between urinary 8-hydroxy-2′-deoxyguanosine (U8-OHdG) level—a marker of oxidative stress—and the incidence of preterm births (PTBs).Design Prospective cohort study.Setting The Japan Environment and Children’s Study (JECS).Participants Data from 92 715 women with singleton pregnancies at and after 22 weeks of gestation who were enrolled in the JECS, a nationwide birth cohort study, between 2011 and 2014 were analysed. U8-OHdG levels were assessed once in the second/third trimester using liquid chromatography–tandem mass spectrometry. Participants were categorised into the following three or five groups: low (

Abstract Background Swallowing/feeding difficulty is a serious hidden health problem in the older population. Although oral intake services based on the degree of this difficulty have been provided and revised in Japanese public long-term care (LTC) insurance since 2006, their implementation has not been examined. We evaluated the impact of policy changes on these services. Methods The nationwide database of LTC service uses in Japan was analysed for three oral intake services: Enhanced Oral Function in daycare facilities whose users were slightly disabled, Maintenance of Oral Ingestion and Transition to Oral Ingestion from tube feeding in residential facilities. Data were extracted for each June from 2015 to 2020 when monthly usage of these services was aligned and each June from 2009 to 2020 for the proportion of users according to LTC insurance certification. The major policy changes were the addition of municipal provision in Enhanced Oral Function and a requirement for multidisciplinary collaboration in Maintenance of Oral Ingestion in 2015. The impact of the medical fee reduction for developing percutaneous gastro-tubing to Transition to Oral Ingestion was also examined. Results Between 2015 and 2020, the use of Enhanced Oral Function and Maintenance of Oral Ingestion increased and Transition to Oral Ingestion decreased, resulting in a total increase in use of 275,000 times or approximately 5,000 times per 100,000 among all older adults with LTC insurance certification. Concerning the proportion of users’ disability status, the major users of Enhanced Oral Function in 2020 were slightly disabled and independent older adults (70%, up from 55% to 2009). Regarding the major users of Maintenance of Oral Ingestion between 2013 and 2020, care-need level 5 (most severe) decreased by 11%, whereas the total of care-need levels 4 and 3 increased by 9%. The use of Transition to Oral Ingestion, which had been declining, showed a further decline after reduction of the medical fee for percutaneous gastro-tubing in 2014. Conclusions Due to policy changes, Enhanced Oral Function and Maintenance of Oral Ingestion have increased in the number of use among slightly disabled persons. However, this increase may be insufficient given the hidden swallowing/feeding difficulty.

Abstract Diagnostic image analysis for unruptured cerebral aneurysms using artificial intelligence has a very high sensitivity. However, further improvement is needed because of a relatively high number of false positives. This study aimed to confirm the clinical utility of tuning an artificial intelligence algorithm for cerebral aneurysm diagnosis. We extracted 10,000 magnetic resonance imaging scans of participants who underwent brain screening using the “Brain Dock” system. The sensitivity and false positives/case for aneurysm detection were compared before and after tuning the algorithm. The initial diagnosis included only cases for which feedback to the algorithm was provided. In the primary analysis, the sensitivity of aneurysm diagnosis decreased from 96.5 to 90% and the false positives/case improved from 2.06 to 0.99 after tuning the algorithm (P

Abstract Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment.

Abstract Purpose To identify the processes of cancer-related pain relief and exacerbation faced by outpatients in an acute care hospital and to examine the support needed for outpatient pain control. Methods We conducted semi-structured, in-depth interviews with patients from the outpatient department of Showa University Northern Yokohama Hospital in Kanagawa Prefecture, Japan. Participants were recruited by purposive sampling. From the recorded data, verbatim transcripts were made and used as textual data for analysis by consistent comparative method. Results Between April 2018 and April 2022, interviews were conducted with 30 participants. Analysis of the verbatim transcripts generated 13 categories from 27 concepts. Category relationships were examined, and a conceptual framework was developed. Outpatients went from being in a state of hesitation towards consultation with medical professionals to receiving individual consistent follow-ups by medical professionals in the hospital and community pharmacies, which led to patient teleconsultations when their physical condition changed, leading to an improvement of pain. Conclusion The process of relief and exacerbation of cancer-related pain experienced by outpatients in the acute care hospital reveals that the provision of consistent follow-up through remote or in-person interviews has an important role to play in pain management, as it helps to build relationships between patients and medical professionals. Alternatively, when outpatients exhibited endurance, their pain worsened, and they fell into a negative cycle of poor pain control.

Abstract Background Lung cancer is the primary cause of cancer mortality and non‐small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases. New drug treatments have been developed since 2010 but there are concerns about the increase in medical costs. This study aimed to compare survival and medical costs among patients with NSCLC according to their initial treatment to estimate the impact of early NSCLC detection. Methods Patients with primary NSCLC who filed insurance claims between April 2013 and March 2019 were identified using the Kyoto City Integrated Database. Patients were divided into two groups depending on their initial treatment: the resection group and drug or radiation group. The survival and medical costs were calculated. Results A total of 2609 patients with primary NSCLC were identified. Among them, 1035 patients underwent resection. The 5‐year survival was 75% for the resection group while below 25% for the drug or radiation group. At 6 months of survival, the median cumulative total cost was 2409 thousand yen (interquartile range [IQR] 1947–4012 thousand yen) in the resection group and 2951 thousand yen (IQR 1600–4706 thousand yen) in the drug or radiation group. At 4 years of survival, the cumulative median total cost was 5257 thousand yen (IQR 3808–8243 thousand yen) in the resection group and 10 202 thousand yen (IQR 4845–20 450 thousand yen) in the drug or radiation group. Conclusions As a first‐line therapy in newly diagnosed patients with NSCLC, surgical resection is associated with longer survival and lower medical costs than pharmacotherapy or radiotherapy.

BackgroundThe International Committee of Medical Journal Editors (ICMJE) has published Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. These provide a global standard for writing and editing medical articles, including research integrity. However, no study has examined the research integrity-related content of Japanese medical journals' Instructions for Authors. We therefore compared research integrity content in ICMJE member journals with those in the English- and Japanese-language journals of the Japanese Association of Medical Sciences (JAMS).Materials and methodsThis was a descriptive literature study. We obtained Instructions for Authors from English- and Japanese-language journals listed on the JAMS website and the ICMJE member journals listed on the ICMJE website as of September 1, 2021. We compared the presence of 20 topics (19 in the ICMJE Recommendations plus compliance with ICMJE) in the Instructions for Authors, and analyzed the content of the conflict of interest disclosure.ResultsWe evaluated 12 ICMJE member journals, and 82 English-language and 99 Japanese-language subcommittee journals. The median number of topics covered was 10.5 for ICMJE member journals, 10 for English-language journals, and three for Japanese-language journals. Compliance with ICMJE was mentioned by 10 (83%) ICMJE member journals, 75 (91%) English-language journals, and 29 (29%) Japanese-language journals. The ICMJE Conflicts of Interest Disclosure Form was requested by seven (64%) ICMJE member journals, 15 (18%) English-language journals, and one (1%) Japanese-language journal.ConclusionsAlthough the topics in the JAMS English-language journals resembled those in the ICMJE member journals, the median value of ICMJE-related topic inclusion was approximately one-third lower in JAMS Japanese-language journals than in ICMJE member journals. It is hoped that Japanese-language journals whose conflict of interest disclosure policies differ from ICMJE standards will adopt international standards to deter misconduct and ensure publication quality.

Objectives We examined literacy related to healthy gestational weight gain (GWG) in immigrant and native Japanese mothers and determined whether it is associated with children’s birth weight.Design Longitudinal cohort study.Setting As the baseline survey in the Japan Environment and Children’s Study (JECS), mothers completed self-administered questionnaires distributed by hand during pregnancy. The self-administered questionnaires used in this study were distributed by mail 6 months after delivery. Children’s birth weight, actual GWG and any complications during delivery were recorded by obstetricians collaborating with JECS.Participants Of 97 452 mothers who consented to participate in the JECS during pregnancy between January 2011 and March 2014, 67 953 were included in this study after exclusions for multiple births, multiple instances of consent by the same pregnant woman, miscarriages/stillbirths or withdrawal from the study within 3 years after participating. In total, 324 immigrant mothers and 963 native Japanese mothers were selected by propensity score matching for analysis.Primary and secondary outcome measures Data were collected on maternal literacy related to healthy GWG at the baseline survey, and data on actual GWG and children’s birth weight were collected by obstetricians. The associations of knowledge about healthy GWG and mothers’ actual GWG with maternal nativity status were examined using a χ2 or Student’s t-test.Results More native Japanese mothers than immigrant mothers knew the appropriate GWG and reason the for needing to know this. Actual GWG was significantly higher among the immigrant mothers, but was within the recommended range. The low birthweight (LBW) incidence was significantly higher among the native mothers.Conclusions Immigrant mothers to Japan had less knowledge about appropriate GWG, but their actual GWG was appropriate and they delivered fewer LBW infants than native Japanese mothers. These findings may indicate the presence of other protective factors for pregnancy or delivery among immigrant mothers.

PurposeThe study aimed to validate and compare coding algorithms for identifying people with migraine within the Japanese claims database.MethodsThis study used the administrative claim database provided by DeSC Healthcare, Inc., that was linked to the results of an online survey administered to adult users of the health app “kencom®.” The ability of the 12 algorithms to detect migraines using diagnostic records alone or with prescription records was evaluated based on sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). We used a migraine diagnosis judged based on respondents' self-reported symptoms according to the diagnostic criteria of the International Classification of Headache Disorders, version 3 (ICHD-3), as true.ResultsOf the 21,480 individuals, 691 had migraine according to the ICHD-3 criteria. The 12 algorithms had a sensitivity of 5.4–8.8%, specificity of 98.8–99.6%, PPVs of 19.2–32.5%, and NPVs of 96.9–97.0%. Algorithm 9 (migraine diagnostic records more than once AND at least one prescription record for migraine prophylaxis or triptans in the same month as diagnosis) produced the highest PPV, whereas Algorithm 2 (at least one diagnostic record of migraine or tension-type headache) had the highest sensitivity. Similar trends were observed when using the ID-Migraine or 4-item migraine screener, instead of the ICHD-3 criteria, for case ascertainment.ConclusionStrict algorithms, such as Algorithm 9, yielded a higher PPV but a lower sensitivity, and such algorithms may be suitable for studies estimating the relative risk. Conversely, algorithms based on a single diagnostic record, such as Algorithm 2, had a higher sensitivity and may be suitable for studies estimating the prevalence/incidence of disease. Our findings will help select a desirable algorithm for migraine studies using a Japanese claim database.

BackgroundPublic concern with regard to over-the-counter (OTC) drug abuse is growing rapidly across countries. OTC drug abuse has serious effects on the mind and body, such as poisoning symptoms, and often requires specialized treatments. In contrast, there is concern about people who potentially abuse OTC drugs whose symptoms are not serious enough to consult medical institutions or drug addiction rehabilitation centers yet are at high risk of becoming drug dependent in the future. ObjectiveConsumer-generated media (CGM), which allows users to disseminate information, is being used by people who abuse (and those who are trying to abuse) OTC drugs to obtain information about OTC drug abuse. This study aims to analyze the content of CGM to explore the questions of people who potentially abuse OTC drugs. MethodsThe subject of this research was Yahoo! Chiebukuro, the largest question and answer website in Japan. A search was performed using the names of drugs commonly used in OTC drug abuse and the keywords overdose and OD, and the number of questions posted on the content of OTC drug abuse was counted. Furthermore, a thematic analysis was conducted by extracting text data on the most abused antitussive and expectorant drug, BRON. ResultsThe number of questions about the content of overdose medications containing the keyword BRON has increased sharply as compared with other product names. Furthermore, 467 items of question data that met the eligibility criteria were obtained from 528 items of text data on BRON; 26 codes, 6 categories, and 3 themes were generated from the 578 questions contained in these items. Questions were asked about the effects they would gain from abusing OTC drugs and the information they needed to obtain the effects they sought, as well as about the effects of abuse on their bodies. Moreover, there were questions on how to stop abusing and what is needed when seeking help from a health care provider if they become dependent. It has become clear that people who abuse OTC drugs have difficulty in consulting face-to-face with others, and CGM is used as a means to obtain the necessary information anonymously. ConclusionsOn CGM, people who abused or tried to abuse OTC drugs were asking questions about their abuse expectations and anxieties. In addition, when they became dependent, they sought advice to quit their abuse. CGM was used to exchange information about OTC drug abuse, and many questions on anxieties and hesitations were posted. This study suggests that it is necessary to produce and disseminate information on OTC drug abuse, considering the situation of those who abuse or are willing to abuse OTC drugs. Support from pharmacies and drugstores would also be essential to reduce opportunities for OTC drug abuse.

Background: The association of maternal antibiotic exposure during pregnancy with childhood allergic diseases remains unclear. Objective: We aimed to evaluate the association of maternal exposure to antibiotic use during pregnancy with childhood allergic diseases up to the age of 3 years by using data from a large Japanese birth cohort. Methods: We analyzed data on 78,678 pregnant women and their offspring aged 0 to 3 years. Prenatal antibiotic exposure was defined as the use of any antimicrobial agent during pregnancy. Information was collected from maternal interviews and medical record transcripts. The outcome variables in this study included preschool asthma, wheezing, food allergy, atopic dermatitis, eczema, allergic rhinoconjunctivitis, and any allergic disease. We used logistic regression analysis to evaluate the association of antibiotic exposure during pregnancy with childhood allergic diseases. Results: Among the participating mothers, 28.5% used antibiotics during pregnancy. Antibiotic exposure during pregnancy was associated with preschool asthma (adjusted odds ratio [aOR] = 1.12 [95% CI = 1.06-1.19]), wheezing (aOR = 1.11 [95% CI = 1.07-1.15]), allergic rhinoconjunctivitis (aOR = 1.10 [95% CI = 1.03-1.17]) and any allergic disease (aOR = 1.09 [95% CI = 1.05-1.14]) in offspring up to age 3 years. In contrast, maternal antibiotic use was not associated with food allergies, atopic dermatitis, or eczema. Additionally, the significant associations were not influenced by the timing of antibiotic exposure, sex of the infants, or maternal history of allergies. Conclusion: Maternal antibiotic exposure during pregnancy is associated with an increased risk of childhood respiratory allergies.