Daijiro Kabata

Improving Outcomes of Witnessed Out‐of‐Hospital Cardiac Arrest After Implementation of International Liaison Committee on Resuscitation 2010 Consensus: A Nationwide Prospective Observational Population‐Based Study

Background The International Liaison Committee on Resuscitation (ILCOR) periodically updates the consensus recommendations for cardiopulmonary resuscitation to improve the outcomes of out‐of‐hospital cardiac arrest (OHCA). However, little is known about the differences in outcomes of witnessed OHCA following the publication of the ILCOR 2010 and the ILCOR 2005 recommendations. Methods and Results We enrolled 241 990 adults who experienced witnessed OHCA between 2007 and 2013 from a prospective, nation‐wide, population‐based cohort database in Japan. We compared neurologically favorable 1‐month survival and 1‐month survival rates post‐OHCA by dividing the study period into 2 categories: the ILCOR 2005 period and ILCOR 2010 period. The associations between guideline periods and outcomes were estimated using multivariable logistic regression analysis and reported as adjusted odds ratio and 95% CI. Among 241 990 patients examined in this study, OHCA was witnessed in 44 706 patients (18%) by emergency medical service personnel and in 197 284 patients (82%) by citizens. Compared with the ILCOR 2005 period, the neurologically favorable 1‐month survival rate improved from 4.6% to 5.2% (adjusted odds ratio, 1.54; 95% CI, 1.42–1.67; P<0.001), and the 1‐month survival rate improved from 9.0% to 9.7% (adjusted odds ratio, 1.34; 95% CI, 1.27–1.42; P<0.001) in the ILCOR 2010 period. These improvements were also shown in patients receiving conventional versus compression‐only cardiopulmonary resuscitation. Conclusions Outcomes of witnessed OHCA were better in the ILCOR 2010 period than those in the ILCOR 2005 period. Our results can provide baseline data for many future prospective studies.

Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study-

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease

Secondary loss of response to adalimumab (ADA‐LOR) commonly occurs in patients with Crohns disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA‐LOR in adult CD patients.

Validation of an algorithm that determines stroke diagnostic code accuracy in a Japanese hospital-based cancer registry using electronic medical records

BackgroundThis study aimed to validate an algorithm that determines stroke diagnostic code accuracy, in a hospital-based cancer registry, using electronic medical records (EMRs) in Japan.MethodsThe subjects were 27,932 patients enrolled in the hospital-based cancer registry of Osaka University Hospital, between January 1, 2007 and December 31, 2015. The ICD-10 (international classification of diseases, 10th revision) diagnostic codes for stroke were extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60); intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient cerebral ischemic attacks and related syndromes and transient cerebral ischemic attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both “definite” and “suspected,” and brain imaging information were extracted from the database. We set the algorithm with the combination of the diagnostic code and/or the brain imaging information, and manually reviewed the presence or absence of the acute cerebrovascular disease with medical charts.ResultsA total of 2654 diagnostic codes, 1991 “definite” and 663 “suspected,” were identified. After excluding duplicates, the numbers of “definite” and “suspected” diagnostic codes were 912 and 228, respectively. The proportion of the presence of the disease in the “definite” diagnostic code was 22%; this raised 51% with the combination of the diagnostic code and the use of brain imaging information. When adding the interval of when brain imaging was performed (within 30xa0days and within 1xa0day) to the diagnostic code, the proportion increased to 84% and 90%, respectively. In the algorithm of “definite” diagnostic code, history of stroke was the most common in the diagnostic code, but in the algorithm of “definite” diagnostic code and the use of brain imaging within 1xa0day, stroke mimics was the most frequent.ConclusionsCombining the diagnostic code and clinical examination improved the proportion of the presence of disease in the diagnostic code and achieved appropriate accuracy for research. Clinical research using EMRs require outcome validation prior to conducting a study.

Association of prophylactic synbiotics with reduction in diarrhea and pneumonia in mechanically ventilated critically ill patients: A propensity score analysis

INTRODUCTIONnThe preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients.nnnMETHODSnCritically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12xa0h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics.nnnRESULTSnWe included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; pxa0<xa00.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; pxa0<xa00.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; pxa0<xa00.001). The incidences of bacteremia did not have significant differences.nnnCONCLUSIONnProphylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Drug-Coated Balloon Angioplasty in Atherosclerosis Patients With Popliteal Artery Involvement:

Purpose: To investigate outcomes of drug-coated balloon (DCB) angioplasty in endovascular interventions including or restricted to the popliteal artery. Methods: A retrospective analysis was conducted of 266 patients [median age 72 years, interquartile range (IQR) 62, 78; 166 men] treated with DCB angioplasty in 281 de novo lesions including the popliteal artery between December 2011 and January 2015 at a single center. The median lesion length was 270 mm (IQR 150, 373). The study outcomes were primary patency and predictors of restenosis [reported as the hazard ratio (HR) with 95% confidence interval (CI)]. Results: The primary patency was 77.4% at a median 12.2 months (IQR 5.7, 18.8). Independent variables associated with restenosis included baseline Rutherford category (HR 1.36, 95% CI 1.05 to 1.77, p=0.02), reference vessel diameter (HR 0.77, 95% CI 0.63 to 0.95, p=0.02), dissection (HR 1.69, 95% CI 1.022.79, p=0.04), and standard nitinol stent use (HR 2.08, 95% CI 1.14 to 3.79, p=0.02). Conclusion: Outcomes after DCB angioplasty in lesions including the popliteal artery were acceptable compared with previous studies. Further investigation with long-term follow-up is needed to confirm these results.

Public attitudes in Japan toward participation in whole genome sequencing studies

BackgroundRecent innovations in gene analysis technology have allowed for rapid and inexpensive sequencing of entire genomes. Thus, both conducting a study using whole genome sequencing (WGS) in a large population and the clinical application of research findings from such studies are currently feasible. However, to promote WGS studies, understanding and voluntary participation by the general public is needed. Therefore, it is essential to investigate the general public’s attitude toward and understanding of WGS studies. The primary goal of our research is to investigate these issues and to discover how they relate to research participation in WGS studies.MethodsA survey of awareness regarding WGS and studies using WGS was conducted with a sample of 2000 or more participants using a self-administered questionnaire posted on the Internet between February 20 and 21, 2015. Prior to the survey, we briefly explained WGS and WGS study-related issues to the respondents in order to provide them with the minimum knowledge required to answer the questionnaire. We then conducted an analysis, including cross-classification.ResultsFor the question regarding interest in WGS, 46.6% of participants responded “Yes.” 70.7% of all respondents said that they were interested in some kinds of findings that could be obtained from WGS studies. Regarding participation in WGS studies, 29.0% were interested in participating. The demographic factors significantly related to attitudes toward research participation were age, level of education, and employment status. The results also suggest that concerns about WGS have a positive effect on people’s willingness to participate. Furthermore, it was shown that for people who were not interested in their gene-related information, concerns about WGS negatively impacted their willingness to participate. However, for people who were interested in their gene-related information, their concerns might not have impacted their willingness to participate.Discussion and conclusionsThis research has shown several key factors that affect the willingness of the general public for the participation to the WGS studies. One of the unexpected findings is that concerns toward WGS studies generally have positive effect on the peoples’ attitude. It will be interesting to further investigate into the various types of concerns that people in different groups have about WGS.

Usefulness of serum biopterin as a predictive biomarker for childhood asthma control: A prospective cohort study

BACKGROUNDnPteridines are metabolites of tetrahydrobiopterin, which serves as co-enzyme of nitric oxide synthase. We sought to investigate the usefulness of pteridines as biomarkers for childhood asthma control.nnnMETHODSnWe conducted a single-center prospective cohort study involving 168 asthmatic children aged 4-17 years who visited the periodical asthma checkup program. Serum neopterin and biopterin levels were measured as pteridines at each visit along with measurement of FeNO, respiratory function tests, nasal eosinophil test, blood eosinophil count, and IgE level. We calculated coefficients for relation between pteridines and asthma control, which was assessed by questionnaires (JPAC: Japanese Pediatric Asthma Control Program).nnnRESULTSnA total of 168 participants aged 10.3xa0±xa03.39 years (meanxa0±xa0SD) with asthma were recruited. The participants in this study contained 58 patients (34.5%) of complete-controlled based on JPAC, 132 patients (76.0%) of well-controlled group based on GINA. FeNO and serum neopterin level did not correlate with following periods JPAC scores. In contrast, serum biopterin level significantly correlated with following periods JPAC total score (Coefficients 0.398; 95% CI 0.164 to 0.632; p value 0.001) and frequency of wheezing during exercise (Coefficients 0.272; 95% CI 0.217 to 0.328; p valuexa0<xa00.001).nnnCONCLUSIONSnWe found serum biopterin effected the following periods control status of asthmatic children, thus monitoring biopterin level will be a useful for management of asthma to adjust treatment.

Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus

Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3u2009MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3u2009MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3u2009MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (Pu2009=u20090.062) but no meaningful mediations of SVDs (Pu2009=u20090.842–0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.

Recovery of Serum Testosterone Levels and Sexual Function in Patients Treated With Short-term Luteinizing Hormone-releasing Hormone Antagonist as a Neoadjuvant Therapy Before External Radiotherapy for Intermediate-risk Prostate Cancer: Preliminary Prospective Study

Introduction External beam radiation therapy (EBRT) with short‐term androgen deprivation therapy is the standard of care for intermediate‐risk prostate cancer patients. However, no study to date has evaluated the hormonal kinetics or sexual and hormonal function recovery after cessation of short‐term luteinizing hormone (LH)‐releasing hormone (LHRH) antagonist treatment. Patients and Methods Ten intermediate‐risk prostate cancer patients (mean age, 69.9 years) were included. All patients received 4 months of LHRH antagonist (degarelix) treatment followed by EBRT. The testosterone, luteinizing hormone (LH), follicle‐stimulating hormone, and prostate‐specific antigen levels were measured and Expanded Prostate Cancer Index Composite questionnaires were completed before LHRH antagonist therapy at baseline; 1, 2, 3, and 4 months after the first injection of LHRH antagonist treatment; and every 2 months thereafter until 18 months. Results The testosterone levels were at the castration level at 1 month after the first LHRH antagonist injection. The median interval to recover a normal testosterone level (> 7.2 nmol/L) was 7 months after the last LHRH antagonist administration. The LH and follicle‐stimulating hormone levels decreased but had increased more than twice above baseline at 15 months after the last LHRH antagonist injection. The sexual function and hormonal bother subdomain scores and sexual and hormonal domain scores decreased once after LHRH antagonist treatment but had significantly recovered thereafter (P < .05). Conclusion In most patients, the testosterone level had normalized within 9 months after the last LHRH administration. Sexual and hormonal function recovered after short‐term LHRH antagonist administration for neoadjuvant therapy before EBRT. Micro‐Abstract No investigation has examined the recovery of serum testosterone or sexual and hormonal function after cessation of luteinizing hormone‐releasing hormone (LHRH) antagonist administration for intermediate‐risk prostate cancer patients before external radiotherapy. The results of the present preliminary prospective study have shown that the serum testosterone level normalized within 9 months after the last LHRH antagonist treatment with gradual recovery of sexual and hormonal function.