Objective : To detect signals of potential drug adverse events (DAEs) through data mining of health insurance claims.
Design and Data : Retrospective observational study. The data used were the database of health insurance claims collected and maintained by the Japan Medical Data Center consisting of 312, 797 medical and pharmaceutical claims in one year (August 2003 through July 2004) linked uniquely for 35, 410 patients using an encryption technique to ensure privacy.
Methods : We counted all combinations (cross product or Cartesian product) of drugs and diagnoses appearing in the same claims and counted the number of times a given drug was prescribed preceding the suspected diagnosis in all combinations of the drug and the diagnosis appearing in a claim, i.e., the prescription date precedes the diagnosing date (the preceding number). We calculated the expected preceding number from the overall prevalence of drugs and diagnoses, and then calculated the observed and expected ratio, which was used as the signal indices. We calculated the signal indices on the health insurance claims data to detect DAEs of psychiatric drugs.
Results : Amoxapine and trazodone HCL showed high signal indices with paralytic ileus and convulsion (epilepsy) as documented in their package inserts. However, paroxetine HCL and etizolam showed high signal indices with these potential adverse events although no such DAEs are documented in their package inserts.
Conclusions : The undocumented high signal indices observed between the drugs and diagnoses indicate the potential DAEs and warrant in-depth pharmacovigilance. Given the strength of health insurance claims with a well-defined source population and accurate drug exposure, the proposed signal index will likely prove to be an effective data mining technique when combined with nested case-control analysis and counter-matching.

Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive com-petitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine phar-macokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluor-ophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same sub-structure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.

Although recent progress in surgery for acute traumatic rupture of the thoracic aorta is encouraging, hospital mortality remains high due to associated fatal lesions. Delayed repair of acute aortic rupture, after management of critical lesions, has been reported in the literature with increasing frequency. We present here a successful operative case of a 54-year-old-woman with acute traumatic aortic rupture. She was admitted to the intensive care unit with loss of consciousness, rib fracture and lung contusion in order to investigate additional critical lesions under strict control of systolic blood pressure under 120mmHg. After completion of all diagnostic procedures, aortic repair was performed 2 days after the accident. The intima of the aorta was found to be disrupted for two thirds of the circumference and pseudoaneurysm was diagnosed. A gelatin-coated vascular prosthesis with one branch was interposed under cardiopulmonary bypass during which general heparinization, systemic hypothermia (20°C) and retrograde brain perfusion method were used. She recovered uneventfully and was discharged 2 weeks after the operation.

The purpose of the present study was to investigate the effects of long-term exercise training on immune function in elderly individuals. This study was conducted on 27 sedentary subjects including 7 males and 20 females aged 66.1±4.2 yrs. (range of 60 to 77 yrs.) who participated in a 12-month exercise program. The subjects attended the exercise program 4.4 ± 1.7 times per month. Peripheral blood samples were taken prior to, and at 5 and 12 months during the exercise training program. Each lymphocyte subset (natural killer: NE, T, cytotoxic T: Tc, helper T: Th, memory-Th and NKT) count in the samples was measured using flow cytometry. Results indicated that NE and Tc cell counts were not significantly altered. Whereas, T and Th cell counts were significantly elevated after 12 months, and memory-Th and NET cell counts were significantly elevated after 5 and 12 months of exercise training. These results suggest that long-term exercise training may be a stimu lus to increase and or maintain immune function in elderly individuals.

A 63-year-old man suffered from type A acute aortic dissection associated with descending thoracic aortic aneurysm and coronary stenosis. He was treated surgically 49 days after onset of acute aortic dissection. Deep hypothermic selective cerebral perfusion was carried out for brain protection. It revealed the aneurysm, 51mm in diameter, located just distal to the aortic arch, and an intimal tear of the dissection located posterior wall of aneurysm. The total arch was replaced with 24mm vascular graft and CABG (LITA-to-seg. 8) was carried out. The postoperative course was uneventful and he was discharged on the 18th postoperative day.

Placenta previa presents a highest risk to pregnancy, and placenta accreta is the most serious. Placenta accreta requires cesarean delivery and often results in massive obstetric hemorrhage and higher maternal morbidity. Challenges associated with cesarean delivery techniques may contribute to increased maternal blood loss and morbidity rates. Several recent obstetric studies reported the usefulness of transverse uterine fundal incision for managing placenta accreta. We present a case of placenta percreta that was treated by a transverse fundal incision. We successfully avoided cutting through the placenta and helped decrease maternal blood loss. After delivery, the patient underwent a cesarean hysterectomy. Postoperative day 48, she experienced watery discharge and was diagnosed with vaginal fistula. We present our case and review the literature.
Hemorrhage ; Humans ; Hysterectomy* ; Placenta ; Placenta Accreta* ; Placenta Previa ; Pregnancy ; Vaginal Fistula*

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data. METHODS: This retrospective cohort study included 149,620 CKD patients aged 40-74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate. RESULTS: During 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT. CONCLUSIONS Among CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.
Aged ; Cohort Studies ; Databases, Factual ; Disease Progression ; Female ; Health Benefit Plans, Employee ; Humans ; Japan/epidemiology* ; Life Style ; Male ; Meals ; Middle Aged ; Proportional Hazards Models ; Renal Insufficiency, Chronic/therapy* ; Renal Replacement Therapy ; Retrospective Studies ; Sleep ; Smoking/epidemiology*