Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

Increased risk of placenta previa and preterm birth in pregnant women with endometriosis/adenomyosis: A propensity-score matching analysis of a nationwide perinatal database in Japan.

AIM: We aimed to investigate the associations of endometriosis and adenomyosis with pregnancy complications by using a large-scale Japanese database. METHODS: We retrospectively analyzed 145 590 singleton pregnancies from the Japan Perinatal Registry Network Database. Pregnant women registered as having endometriosis or adenomyosis were designated as the case group (EA), whereas the control group (non-EA) was selected using propensity-score matching adjusted for variables such as age, parity, BMI, smoking history, and the use of assisted reproductive technology. The main outcomes included placental malposition, preterm birth, and hypertensive disorders of pregnancy (HDP). RESULTS: In total, 1203 patients from both the EA and non-EA groups were matched and evaluated. The EA group showed significantly higher rates of placenta previa (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.84-4.92), low-lying placenta (OR, 2.02; 95% CI, 1.06-3.86), and preterm birth (OR, 1.44; 95% CI, 1.13-1.84) than the non-EA group. However, no significant difference was observed in the incidence of HDP (OR, 1.22; 95% CI, 0.90-1.66). CONCLUSION: The use of propensity-score matching to analyze a nationwide perinatal database in Japan clarified that EA was associated with increased pregnancy complications, specifically placental malposition, including placenta previa and low-lying placenta, and preterm birth, but not with HDP.

Heterogeneous treatment effects of adjuvant therapy for patients with cervical cancer in the intermediate-risk group.

BACKGROUND: The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC-IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC-IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics. METHODS: We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB-IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score-matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non-adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs. RESULTS: Among the 1613 patients with CC-IR, 619 and 994 were in the non-treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3-year progression-free survival (PFS) rates were 88.1% and 90.3% in the non-treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3-year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors. CONCLUSION: Adjuvant therapy is optional for some patients with CC-IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors.

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer.

BACKGROUND: Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent. METHODS: Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage. RESULTS: A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev. CONCLUSIONS: This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.

Impact of lung function impairment after allogeneic hematopoietic stem cell transplantation.

Late-onset noninfectious pulmonary complications (LONIPC) are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). However, the clinical impact of lung function deterioration itself in long-term adult survivors of HSCT remains to be fully investigated. This retrospective, longitudinal study aimed to investigate pulmonary function following HSCT in terms of its change and the clinical significance of its decline. We examined 167 patients who survived for at least 2 years without relapse. The median follow-up period was 10.3 years. A linear mixed-effects model showed that the slope of pulmonary function tests values, including percent vital capacity (%VC), percent forced expiratory volume in one second (%FEV1), and FEV1/forced VC ratio (FEV1%), decreased over time. The cumulative incidence of newly obstructive and restrictive lung function impairment (LFI) at 10 years was 15.7% and 19.5%, respectively. Restrictive LFI was a significant, independent risk factor for overall survival (hazard ratio 7.11, P = 0.007) and non-relapse mortality (hazard ratio 12.19, P = 0.003). Our data demonstrated that lung function declined over time after HSCT and that the decline itself had a significant impact on survival regardless of LONIPC.

Acceptance, Barriers, and Facilitators to Implementing Artificial Intelligence-Based Decision Support Systems in Emergency Departments: Quantitative and Qualitative Evaluation.

BACKGROUND: Despite the increasing availability of clinical decision support systems (CDSSs) and rising expectation for CDSSs based on artificial intelligence (AI), little is known about the acceptance of AI-based CDSS by physicians and its barriers and facilitators in emergency care settings. OBJECTIVE: We aimed to evaluate the acceptance, barriers, and facilitators to implementing AI-based CDSSs in the emergency care setting through the opinions of physicians on our newly developed, real-time AI-based CDSS, which alerts ED physicians by predicting aortic dissection based on numeric and text information from medical charts, by using the Unified Theory of Acceptance and Use of Technology (UTAUT; for quantitative evaluation) and the Consolidated Framework for Implementation Research (CFIR; for qualitative evaluation) frameworks. METHODS: This mixed methods study was performed from March to April 2021. Transitional year residents (n=6), emergency medicine residents (n=5), and emergency physicians (n=3) from two community, tertiary care hospitals in Japan were included. We first developed a real-time CDSS for predicting aortic dissection based on numeric and text information from medical charts (eg, chief complaints, medical history, vital signs) with natural language processing. This system was deployed on the internet, and the participants used the system with clinical vignettes of model cases. Participants were then involved in a mixed methods evaluation consisting of a UTAUT-based questionnaire with a 5-point Likert scale (quantitative) and a CFIR-based semistructured interview (qualitative). Cronbach α was calculated as a reliability estimate for UTAUT subconstructs. Interviews were sampled, transcribed, and analyzed using the MaxQDA software. The framework analysis approach was used during the study to determine the relevance of the CFIR constructs. RESULTS: All 14 participants completed the questionnaires and interviews. Quantitative analysis revealed generally positive responses for user acceptance with all scores above the neutral score of 3.0. In addition, the mixed methods analysis identified two significant barriers (System Performance, Compatibility) and two major facilitators (Evidence Strength, Design Quality) for implementation of AI-based CDSSs in emergency care settings. CONCLUSIONS: Our mixed methods evaluation based on theoretically grounded frameworks revealed the acceptance, barriers, and facilitators of implementation of AI-based CDSS. Although the concern of system failure and overtrusting of the system could be barriers to implementation, the locality of the system and designing an intuitive user interface could likely facilitate the use of optimal AI-based CDSS. Alleviating and resolving these factors should be key to achieving good user acceptance of AI-based CDSS.

Prognosis of high-risk human papillomavirus-related cervical lesions: A hidden Markov model analysis of a single-center cohort in Japan.

INTRODUCTION: Previous studies have shown that individuals with human papillomavirus (HPV)-related cervical lesions have different prognoses according to the HPV genotype. However, these studies failed to account for possible diagnostic misclassification. In this retrospective cohort study, we aimed to clarify the natural course of cervical lesions according to HPV genotype to account for any diagnostic misclassification. MATERIALS AND METHODS: Our cohort included 729 patients classified as having cervical intraepithelial neoplasia (CIN). HPV was genotyped in all patients, who were followed up or treated for cervical lesions at the University of Tokyo Hospital from October 1, 2008 to March 31, 2015. Hidden Markov models were applied to estimate the diagnostic misclassification probabilities of the current diagnostic practice (histology and cytology) and the transitions between true states. We then simulated two-year transition probabilities between true cervical states according to HPV genotype. RESULTS: Compared with lesions in patients with other HPV genotypes, lesions in HPV 16-positive patients were estimated to be more likely to increase in severity (i.e., CIN3/cancer); over 2 years, 17.7% (95% confidence interval [CI], 9.3%-29.3%) and 27.8% (95% CI, 16.6%-43.5%) of those with HPV 16 progressed to CIN3/cancer from the true states of CIN1 and CIN2, respectively, whereas 55%-70% of CIN1/2 patients infected with HPV 52/58 remained in the CIN1/2 category. Misclassification was estimated to occur at a rate of 3%-38% in the current diagnostic practice. CONCLUSION: This study contributes robust evidence to current literature on cervical lesion prognosis according to HPV genotype and quantifies the diagnostic misclassification of true cervical lesions.

Risk factors of sepsis among patients with qSOFA<2 in the emergency department.

OBJECTIVE: Studies have suggested that qSOFA can be used for early detection of sepsis immediately upon arrival at the emergency department (ED). Despite this, little is known about the risk factors associated with the subsequent diagnosis of sepsis among patients with qSOFA<2 in the ED. METHODS: This is a retrospective cohort study using ED data from a large tertiary medical center in Japan, 2018-2020. We included adult patients (aged ≥18 years) presenting to the ED with suspected infection (e.g., having a fever) and qSOFA<2. We identified patients who developed sepsis based on the Sepsis-3 criteria, and compared patient characteristics (e.g., demographics, vital signs upon the initial triage, chief complaint, and comorbidities) between patients who developed sepsis or not. Additionally, we identified the potential risk factors of sepsis among patients with qSOFA<2 using a multivariable logistic regression model. RESULTS: We identified 151 (7%) patients who developed sepsis among 2025 adult patients with suspected infection and qSOFA<2. Compared with patients who did not develop sepsis, patients who developed sepsis were likely to be older and have vital signs suggestive of imminent sepsis (e.g., high respiratory rate). In the multivariable logistic regression model, the potential risk factors of sepsis among patients with qSOFA<2 were older age (adjusted OR, 1.92 [95%CI 1.19-3.19]), vital signs suggestive of imminent sepsis (e.g., adjusted OR of altered mental status, 3.50 [95%CI 2.25-5.50]), receipt of oxygen therapy upon arrival at the ED (adjusted OR, 1.91 [95%CI 1.38-2.26]), chief complaint of sore throat (adjusted OR, 2.15 [95%CI 1.08-4.13]), and the presence of comorbid diabetes mellitus, ischemic heart disease, and chronic kidney disease (e.g., adjusted OR of diabetes mellitus, 1.47 [95%CI 1.10-1.96]). On the contrary, chief complaint of abdominal and chest pain were associated with a lower risk of sepsis (e.g., adjusted OR of abdominal pain, 0.26 [95%CI 0.14-0.45]). CONCLUSIONS: We found that older age, vital signs prognosticating sepsis, and the presence of some comorbidities were the potential risk factors of sepsis in patients with qSOFA<2. These potential risk factors could be useful to efficiently recognize patients who might develop sepsis in the ED.

Adherence to Daily, Weekly, and Monthly Dosing Regimens of Bisphosphonates for Osteoporosis Treatment in Postmenopausal Women in Japan: A Retrospective Study Using Claims Data.

Poor medication adherence of osteoporosis patients is a major global medical problem because of its negative impact on health outcomes and quality of life. The aim of this study was to evaluate how differences in dosing regimens influence adherence to oral bisphosphonates using data from a large health insurance provider in Japan. This was a retrospective observational study using claims data obtained between October 2012 and January 2018, from the community-based National Health Insurance program of a large city in Japan. The data included in the analysis were obtained from women 60 to 74 years old whose oral bisphosphonate prescription was detected between April 2013 and February 2017. Treatment adherence was monitored from the initial prescription for one year, i.e., up to January 2018. Primary comparisons among the daily-dosing, weekly-dosing, and monthly-dosing groups were based on the mean medication possession ratio (MPR). Data from a total of 3,958 patients were analyzed. The numbers of patients aged 60-64, 65-69, and 70-74 were 425, 1,400, and 2,133, respectively. The highest mean MPR was 69.4% for the monthly-dosing of bisphosphonates, followed by the weekly-dosing at 63.5%, and daily-dosing at 57.2%. Using the Kruskal-Wallis test with Dunn-Bonferroni correction, there were significant differences in mean MPR for daily versus weekly (p < 0.01), daily versus monthly (p < 0.001), and weekly versus monthly dosing regimens (p < 0.05). These results suggest significantly more patients adhere to a monthly or weekly regimen of bisphosphonates in the treatment of osteoporosis than to a daily regimen.

Knowledge, Experience, and Perceptions of Generic Drugs among Middle-Aged Adults and their Willingness-to-Pay: A Nationwide Online Survey in Japan.

Promoting generic drugs can reduce the financial burden on patients and improve healthcare finances. The insurers have been conducting promotional efforts, such as direct-mail campaigns, but little is known about the public's perception of generic drugs and effective message strategies for promotion. In 2018, we conducted a web-based survey of middle-aged Japanese men and women that investigated: (i) their perceptions of generic drugs, (ii) the association between perceptions and willingness-to-pay for brand-name drugs relative to generic drugs, and (iii) potentially effective forms of information provision to alter individuals' perceptions. Of the 1,005 respondents, over half perceived generic drugs as having the same level of efficacy and safety as brand-name drugs. While willingness-to-pay was dispersed among respondents, two factors were associated with small willingness-to-pay: (a) perceiving generic drugs as having the same level of efficacy and safety as brand-name drugs and (b) perceiving that promoting the use of generic drugs is important for controlling medical expenditures. Moreover, presenting potential savings over five years by choosing generic drugs was a potentially effective tool for altering perceptions, relative to showing monthly savings. Our findings suggest that certain parts of the population still have high willingness-to-pay for brand-name drugs, and strategic communication to alter perception could be effective in promoting the use of generic drugs among those who are price-inelastic.

Claims-based algorithms for common chronic conditions were efficiently constructed using machine learning methods.

Identification of medical conditions using claims data is generally conducted with algorithms based on subject-matter knowledge. However, these claims-based algorithms (CBAs) are highly dependent on the knowledge level and not necessarily optimized for target conditions. We investigated whether machine learning methods can supplement researchers' knowledge of target conditions in building CBAs. Retrospective cohort study using a claims database combined with annual health check-up results of employees' health insurance programs for fiscal year 2016-17 in Japan (study population for hypertension, N = 631,289; diabetes, N = 152,368; dyslipidemia, N = 614,434). We constructed CBAs with logistic regression, k-nearest neighbor, support vector machine, penalized logistic regression, tree-based model, and neural network for identifying patients with three common chronic conditions: hypertension, diabetes, and dyslipidemia. We then compared their association measures using a completely hold-out test set (25% of the study population). Among the test cohorts of 157,822, 38,092, and 153,608 enrollees for hypertension, diabetes, and dyslipidemia, 25.4%, 8.4%, and 38.7% of them had a diagnosis of the corresponding condition. The areas under the receiver operating characteristic curve (AUCs) of the logistic regression with/without subject-matter knowledge about the target condition were .923/.921 for hypertension, .957/.938 for diabetes, and .739/.747 for dyslipidemia. The logistic lasso, logistic elastic-net, and tree-based methods yielded AUCs comparable to those of the logistic regression with subject-matter knowledge: .923-.931 for hypertension; .958-.966 for diabetes; .747-.773 for dyslipidemia. We found that machine learning methods can attain AUCs comparable to the conventional knowledge-based method in building CBAs.

Initial assessment in emergency departments by chief complaint and respiratory rate.

BACKGROUND: Understanding heterogeneity of the respiratory rate (RR) as a risk stratification marker across chief complaints is important to reduce misinterpretation of the risk posed by outcome events and to build accurate risk stratification tools. This study was conducted to investigate the associations between RR and clinical outcomes according to the five most frequent chief complaints in an emergency department (ED): fever, shortness of breath, altered mental status, chest pain, and abdominal pain. METHODS: This retrospective cohort study examined ED data of all adult patients who visited the ED of a tertiary medical center during April 2018-September 2019. The primary exposure was RR at the ED visit. Outcome measures were hospitalization and mechanical ventilation use. We used restrictive cubic spline and logistic regression models to assess the association of interest. RESULTS: Of 16 956 eligible ED patients, 4926 (29%) required hospitalization; 448 (3%) required mechanical ventilation. Overall, U-shaped associations were found between RR and the risk of hospitalization (eg, using RR = 16 as the reference, the odds ratio [OR] of RR = 32, 6.57 [95% CI 5.87-7.37]) and between RR and the risk of mechanical ventilation. This U-shaped association was driven by patients' association with altered mental status (eg, OR of RR = 12, 2.63 [95% CI 1.25-5.53]). For patients who have fever or shortness of breath, the risk of hospitalization increased monotonously with increased RR. CONCLUSIONS: U-shaped associations of RR with the risk of overall clinical outcomes were found. These associations varied across chief complaints.

Association of Initial Potassium Levels with the Type of Stroke in the Emergency Department.

Serum potassium levels are considered as a marker of cerebrovascular emergencies but there is less clarity on the association between initial serum potassium levels recorded on patient's arrival at the emergency department with the type of stroke. This is a case-control study using data of a tertiary care hospital in Japan from April 2018 to September 2019. We identified adult patients with hemorrhagic stroke including subarachnoid hemorrhage (cases) and those with ischemic stroke (controls). Data on age, sex, chief complaints, vital signs, and initial blood tests were collected. We analyzed the association between serum potassium levels and the type of stroke by drawing a LOWESS curve. Additionally, we fitted a logistic regression model to examine the association of interest. There were 416 stroke patients (158 hemorrhagic and 258 ischemic). The median age was 77 years (IQR: 68, 84), and 54% were male. The mean potassium level was 3.69 ± 0.55 mEq/L for hemorrhagic stroke and 4.08 ± 0.65 mEq/L for ischemic stroke. The LOWESS curve showed that the lower initial potassium level was linearly associated with a greater likelihood of hemorrhagic stroke. In the logistic regression model, the odds ratio for the risk of hemorrhagic stroke per 1 mEq/L lower potassium level was 3.31 (95% confidence interval [CI]: 2.24-5.04). This association remained significant in a multivariable model adjusting for other covariates (OR: 2.62 [95% CI: 1.70-4.16]). Initial potassium level was lower in patients with hemorrhagic stroke compared to those with ischemic stroke.

Clinical performance of early warning scoring systems for identifying sepsis among anti-hypertensive agent users.

BACKGROUND: Little is known about the accuracy of the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS) in identifying sepsis patients with a history of hypertension on anti-hypertensive agents, which affect vital signs as components of the scoring systems. We aimed to examine the ability of qSOFA and NEWS to predict sepsis among anti-hypertensive agent users by comparing them with non-users. METHODS: We retrospectively identified adult patients (aged ≥18years) with suspected infection who presented to an emergency department (ED) of a large tertiary medical center in Japan between April 2018 and March 2020. Suspected infection was defined based on the chief complaint of fever, high body temperature, or the clinical context on arrival at the ED. We excluded patients who had trauma or cardiac arrest, those who were transported to other hospitals after arrival at the ED, and those whose vital signs data were mostly missing. The predictive performances of qSOFA and NEWS based on initial vital signs were examined separately for sepsis, ICU admission, and in-hospital mortality and compared between anti-hypertensive agent users and non-users. RESULTS: Among 2900 patients with suspected infection presenting to the ED, 291 (10%) had sepsis, 1023 (35%) were admitted to the ICU, and 188 (6.5%) died. The prediction performances of qSOFA and NEWS for each outcome among anti-hypertensive agent users were lower than that among non-users (e.g., c-statistics of qSOFA for sepsis, 0.66 vs. 0.71, p = 0.07; and for ICU admission, 0.70 vs. 0.75, p = 0.01). For identifying sepsis, the sensitivity and specificity of qSOFA ≥2 were 0.43 and 0.77 in anti-hypertensive agent users and 0.51 and 0.82 in non-users. Similar associations were observed for identifying ICU admission and in-hospital mortality. Regardless of the use of anti-hypertensive agents, NEWS had better prediction abilities for each outcome than qSOFA. CONCLUSION: The clinical performance of qSOFA and NEWS for identifying sepsis among anti-hypertensive agent users was likely lower than that among non-users.

Institution-Specific Machine Learning Models for Prehospital Assessment to Predict Hospital Admission: Prediction Model Development Study.

BACKGROUND: Although multiple prediction models have been developed to predict hospital admission to emergency departments (EDs) to address overcrowding and patient safety, only a few studies have examined prediction models for prehospital use. Development of institution-specific prediction models is feasible in this age of data science, provided that predictor-related information is readily collectable. OBJECTIVE: We aimed to develop a hospital admission prediction model based on patient information that is commonly available during ambulance transport before hospitalization. METHODS: Patients transported by ambulance to our ED from April 2018 through March 2019 were enrolled. Candidate predictors were age, sex, chief complaint, vital signs, and patient medical history, all of which were recorded by emergency medical teams during ambulance transport. Patients were divided into two cohorts for derivation (3601/5145, 70.0%) and validation (1544/5145, 30.0%). For statistical models, logistic regression, logistic lasso, random forest, and gradient boosting machine were used. Prediction models were developed in the derivation cohort. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) and association measures in the validation cohort. RESULTS: Of 5145 patients transported by ambulance, including deaths in the ED and hospital transfers, 2699 (52.5%) required hospital admission. Prediction performance was higher with the addition of predictive factors, attaining the best performance with an AUROC of 0.818 (95% CI 0.792-0.839) with a machine learning model and predictive factors of age, sex, chief complaint, and vital signs. Sensitivity and specificity of this model were 0.744 (95% CI 0.716-0.773) and 0.745 (95% CI 0.709-0.776), respectively. CONCLUSIONS: For patients transferred to EDs, we developed a well-performing hospital admission prediction model based on routinely collected prehospital information including chief complaints.

Validation of chief complaints, medical history, medications, and physician diagnoses structured with an integrated emergency department information system in Japan: the Next Stage ER system.

AIM: Emergency department information systems (EDIS) facilitate free-text data use for clinical research; however, no study has validated whether the Next Stage ER system (NSER), an EDIS used in Japan, accurately translates electronic medical records (EMRs) into structured data. METHODS: This is a retrospective cohort study using data from the emergency department (ED) of a tertiary care hospital from 2018 to 2019. We used EMRs of 500 random samples from 27,000 ED visits during the study period. Through the NSER system, chief complaints were translated into 231 chief complaint categories based on the Japan Triage and Acuity Scale. Medical history and physician's diagnoses were encoded using the International Classification of Diseases, 10th Revision; medications were encoded as Anatomical Therapeutic Chemical Classification System codes. Two reviewers independently reviewed 20 items (e.g., presence of fever) for each study component (e.g., chief complaints). We calculated association measures of the structured data by the NSER system, using the chart review results as the gold standard. RESULTS: Sensitivities were very high (>90%) in 17 chief complaints. Positive predictive values were high for 14 chief complaints (≥80%). Negative predictive values were ≥96% for all chief complaints. For medical history and medications, most of the association measures were very high (>90%). For physicians' ED diagnoses, sensitivities were very high (>93%) in 16 diagnoses; specificities and negative predictive values were very high (>97%). CONCLUSIONS: Chief complaints, medical history, medications, and physician's ED diagnoses in EMRs were well-translated into existing categories or coding by the NSER system.

Clinical outcomes in donors and recipients of kidney transplantations involving medically complex living donors - a retrospective study.

We retrospectively compared the post-transplantation graft survival and the donor's estimated glomerular filtration rates (eGFRs) following living donor kidney transplantations (LDKTs) involving medically complex living donors (MCLDs) (the elderly and patients with obesity, hypertension, diabetes mellitus, or reduced renal function) and standard living donors (SLDs). The clinical data on patients who underwent LDKTs at our institution from 2006-2019, including 192 SLDs and 99 MCLDs, were evaluated. Regarding recipients, the log-rank test and multivariable Cox proportional hazards analyses showed a higher incidence of overall and death-censored graft loss in the recipients who received kidneys from MCLDs (Hazard ratio = 2.16 and 3.25, P = 0.015 and 0.004, respectively), after adjusting for recipient-related variables including age, sex, duration of dialysis, ABO compatibility, and donor-specific antibody positivity. Regarding donors, a linear mixed model showed significantly lower postdonation eGFRs (-2.25 ml/min/1.73 m2 , P = 0.048) at baseline in MCLDs than SLDs, but comparable change (difference = 0.01 ml/min/1.73 m2 /year, P = 0.97). In conclusion, although kidneys from MCLDs are associated with impaired graft survival, the donation did not adversely affect the MCLDs' renal health in at least the short-term. LDKTs involving carefully selected MCLDs would be an acceptable alternative for recipients with no SLDs.

Radiation therapy and the risk of herpes zoster in patients with cancer.

BACKGROUND: The role and impact of radiation therapy (RT) on the development of herpes zoster (HZ) has not been well studied. The objective of this study was to investigate the association between RT and HZ. METHODS: A propensity score-matched, retrospective cohort study was conducted using institutional cancer registry data and medical records from 2011 to 2015. The risk of developing HZ in the RT and non-RT groups was compared using a Cox proportional hazards model. Associations also were explored between the RT field and the anatomic location of HZ in patients who developed HZ after RT. The expected number of HZ events within the radiation field was calculated according to the RT received by each patient; then, this number was compared with the observed number of in-field events. RESULTS: Of 17,655 patients, propensity score matching yielded 4350 pairs; of these, 3891 pairs were eligible for comparison. The cumulative incidence of HZ in the RT group (vs the non-RT group) during the first 5 years after the index date was 2.1% (vs 0.7%) at 1 year, 3.0% (vs 1.0%) at 2 years, 3.4% (vs 1.3%) at 3 years, 4.1% vs 1.7% at 4 years, and 4.4% vs 1.8% at 5 years. The RT group showed a significantly higher risk of HZ than the non-RT group (hazard ratio, 2.59, 95% CI, 1.84-3.66). In the 120 patients who developed HZ after RT, HZ events were observed significantly more frequently within the RT field than expected (74 vs 43.8 events; P < .001). CONCLUSIONS: Patients with cancer who received RT showed a significantly higher risk of HZ, which was commonly observed within the radiation field.

Heterogeneous impact of cytomegalovirus reactivation on nonrelapse mortality in hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) infection is a major complication in allogeneic stem cell transplantation. The utility of CMV prophylaxis with letermovir has been reported; however, the specific applications remain unclear. In this study, we retrospectively analyzed large-scale registry data (N = 10 480) to clarify the risk factors for nonrelapse mortality (NRM) in connection with CMV reactivation. First, we identified risk factors for CMV reactivation using multivariate analysis and developed a scoring model. Although the model effectively stratified reactivation risk into 3 groups (43.7% vs 60.9% vs 71.5%; P < .001), the 3-year NRM was significantly higher in patients with CMV reactivation, even in the low (20.9% vs 13.0%, P < .001), intermediate (21.4% vs 15.6%; P < .001), and high (29.3% vs 18.0%; P < .001) reactivation risk groups. Next, survival analysis considering competing risks, time-dependent covariates, and interaction terms for exploring the heterogeneous impact of CMV reactivation on NRM in the training cohort revealed that chronic myeloid leukemia (CML) (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.05-2.96; P = .033), good performance status (PS) (HR, 1.42; 95% CI, 1.04-1.94; P = .028), HLA-matched donor (HR, 1.34; 95% CI, 1.06-1.70; P = .013), and standard-risk disease (HR, 1.28; 95% CI, 1.04-1.58; P = .022) were associated with increased NRM. In the test cohort, CMV reactivation was significantly associated with increased 3-year NRM among patients with 2 to 4 factors (22.1% vs 13.1%; P < .001) but was comparable among patients with 0 or 1 factor (23.2% vs 20.4%; P = .62). We propose that CMV prophylaxis should be determined based on reactivation risk, as well as these other factors.

Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia.

BACKGROUND: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. METHODS: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes-HPV 16, 18, 52, and 58-were investigated. RESULTS: The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1. CONCLUSIONS: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.