Appropriate observational studies with sufficient external validity are apparently warranted to assess comparative effectiveness and safety of treatment with approved drugs in real world clinical practice. This kind of study must register patients consecutively without any arbitrariness, assess outcome carefully, (e.g. cardiovascular events) and automatically extract clinical data including results from laboratory tests and prescribed drugs. Clinical trials for the assessment of efficacy of newly developing drugs may also need such patients' registry. Data storage system by SS-MIX may be appropriate for this purpose. (Jpn J Pharmacoepidemiol 2013；18(1)：31-34)

　Clinical research skills to answer clinical questions arising in daily clinical practice are necessary to improve the quality of medical care. Since 2014, we have been developing a clinical research educational program including clinical research fellowships for doctors, nurses, and pharmacists at the Department of Clinical Research and Quality Management. This paper reports intermediate educational activities and evaluations.

A 27-year-old man who presented with worsening dyspnea was transferred to our hospital due to congestive heart failure with multiple organ dysfunction. Echocardiogram showed severe left ventricular systolic dysfunction and a huge thrombus in the left ventricle. An urgent operation was performed to remove the thrombus simultaneously with the placement of bilateral extracorporeal ventricular assist devices. After the operation, despite a rapid improvement in the liver function, renal dysfunction persisted and he remained anuric for nearly a month. We continued maximal circulatory support with biventricular assist device to optimize his end-organ function. His renal function gradually improved, allowing him to be registered as a heart transplant candidate on the 140th postoperative day. On the 146th postoperative day, the patient underwent successful removal of the right ventricular assist device, and the left extracorporeal device was replaced by an implantable device (HeartMate II). He was discharged 78 days after the implantation. We present here a case where adequate support with biventricular assist device enabled a successful bridge to transplantation even in a patient with end-stage heart failure having end-organ dysfunction.

Background : Acute massive pulmonary embolism is a life-threatening disease. It is often treated with thrombolytic therapy, however, the mortality rates are unsatisfactorily high in patients who developed shock and subsequent cardiac arrest. Surgical pulmonary embolectomy is a last resort for patients with hemodynamic instability. We studied the outcomes of our patients who underwent pulmonary embolectomy for acute pulmonary embolism. Methods : Eight patients who underwent pulmonary embolectomy between January 2011 and December 2014 were studied. Our surgical indications were as follows. Patients who experienced cardiac arrest and treated with PCPS, and those in persistent vital shock, with contraindications of thrombolytic therapy, or with right heart floating thrombus. However, patients with ischemic encephalopathy or acute exacerbation of chronic thromboembolic pulmonary hypertension, and those who had already been treated with thrombolytic therapy were excluded. Preoperative ECMO was indicated for those in sustained shock. Pulmonary embolectomy was performed through median sternotomy and with cardiopulmonary bypass. After antegrade cardiac arrest, all clots were removed with forceps under direct vision through incisions in the bilateral main pulmonary arteries. IVC filter (Günther Tulip) was placed through the right atrial appendage. In our early cases, IVC filter (Neuhaus Protect) was placed after chest closure. Anticoagulation was not administered until hemostasis was achieved. Results : Seven patients underwent pulmonary embolectomy for massive pulmonary embolism, and in one patient pulmonary embolectomy was indicated for right heart floating thrombi although the pulmonary embolism was submassive. Three patients underwent cardiopulmonary resuscitation and were treated with ECMO. Other 3 patients in sustained shock vital were electively treated with ECMO. The other patient developed cardiopulmonary arrest shortly after anesthetic induction and intubation, and suffered disturbance of consciousness postoperatively. All patients were successfully weaned from cardiopulmonary bypass and underwent IVC filter placement (5 Neuhaus Protect, and 3 GProtec Tulip). One patient died due to a vascular complication associated with catheter insertion (retroperitoneal hematoma). No patients developed residual pulmonary hypertension. There were postoperative complications including pneumonia in 5 patients, tracheostomy in 2 patients, atrial fibrillation in 3 patients, and pericardial effusion in 1 patient. One patient who suffered disturbance of consciousness died 2.4 months after the surgery. Other patients had not developed any thrombotic and hemorrhagic complications during a median follow-up of 13.1 months. Conclusions : Pulmonary embolectomy is an effective treatment of acute massive pulmonary embolism. We believe that our strategy is useful, consisting of preoperative hemodynamic stability by an institution of ECMO, complete removal of clots by bilateral main pulmonary incisions, and prevention of recurrence by IVC filter placement.

The Standardized Structured Medical record Information eXchange (SS-MIX) was started in 2006 as the project supported by the Ministry of Health, Labour and Welfare (MHLW) for promoting the exchange of the standardized medical information. Free soft wares developed in the project allow the storage of medical information to receive HL7 messages for prescription, laboratory test results, diagnoses and patient demographics in the hospital information system (HIS). We encourage the use of the SS-MIX standardized storage for postmarketing surveys and clinical studies. The recommendations consist of the following 7 parts. [1] In surveys and clinical studies, the information of drugs and laboratory test results in the SS-MIX standardized storage can be directly transferred to the electronic questionnaire and the investigators may obtain the information with high accuracy and granularity. [2] The SS-MIX standardized storage works as the backup system for the HIS because it can provide the minimum information essential in patient care even under the disastrous condition like earthquake or unexpected network failure. [3] The SS-MIX standardized storage may be useful to conduct a good pharmacoepidemiology study not only because it provides the information in the storage efficiently but also it can be used to identify “new users” who started the drug after some period of non-use.The “new user” design is often essential to have the unbiased results. [4] When the drug company conducts postmarketing surveys according to the current regulation, the use of the SS-MIX standardized storage will facilitate the fast and efficient collection of data to develop the timely measure to minimize the drug-related risk. With the SS-MIX standardized storage, it is also expected that many types of study design can be employed and the quality of data is improved in the survey. [5] The SS-MIX standardized storage maybe also useful to evaluate the risk minimization action plan by comparing the prescription pattern or incidence of the targeted adverse event between two periods before and after the implementation of the action plan. [6] In planning clinical trials, the SS-MIX standardized storage may be used to estimate the size of eligible patients. The storage may also allow conducting cross-sectional studies to know characteristics of diseases or drug treatment. In addition, cohorts of those who had coronary artery angiography, new users of a drug and those with a rare disease may be readily identified. Using such cohorts, investigators can initiate a case-control study nested within the cohort, pharmacogenomic studies and comparative effectiveness researches. [7] The SS-MIX standardized storage may be used as the formal data source in clinical trials in the future when some conditions are satisfied. For instance, the formal agreement should be reached between industry, government and academia on the use of standards of data structure in Clinical Data Interchange Standards Consortium (CDISC) and on the operation of computerized system validation (CSV) in the clinical trials.

The venerable drug colchicine has garnered significant recent attention due to its endorsement by the United States Food and Drug Administration as an anti-inflammatory medication for cardiovascular diseases. However, the administration of this drug at its minimal available dose of 0.5 mg has been associated with certain adverse reactions.Once colchicine is administered, the drug disappears from blood in a short time and distributes in the leukocytes for a certain period of time that elicits anti-inflammatory effect.Consequently, an in-depth comprehension of the pharmacokinetics of lower dosages within leukocytes assumes important for its broader application in routine clinical contexts. In this study, we present a comprehensive analysis of the pharmacological disposition of colchicine in the plasma, polymorphonuclear leukocytes, and mononuclear leukocytes among healthy Japanese male subjects, following both single and multiple oral administrations of 0.5 mg and 0.25 mg doses of colchicine. Our investigation reveals that colchicine persists within leukocyte populations even when administered at reduced dosages. The findings herein hold promise for mitigating the adverse effects associated with its use in the treatment of inflammatory cardiovascular disorders.

A 60-year-old man complained of palpitation due to transitory atrial fibrillation. The annulo-aortic ectasia was recognized, and was getting enlarged to 52 mm. After an additional examination, membranous ventricular septal aneurysm was revealed. There was no evidence of thrombus, shunt, or infection in the membranous ventricular septal aneurysm. The valve-sparing aortic root replacement (reimplantation) and the patch-closure of the membranous ventricular septal aneurysm were performed. Stabilizing the subannular tissue by a Dacron patch made the reimplantation technique feasible. To secure a subannular suture line, 3 mattress stitches were passed inside-out through the Dacron patch, the fibrous rim of the membranous septum and the prosthetic graft again. He was discharged without any complication 12 days after the operation.

We evaluated body constituents patterns of 74 consecutive patients with neurological degenerative disorders. They comprise Parkinson's disease (n = 38), amyotrophic lateral sclerosis (n = 19), and multiple system atro­phy (n = 17). We compared body constituents patterns between them and 149 consecutive patients with other neurological diseases of the same age. We used ki-ketsu-sui scores to evaluate body constituents patterns in all cases. Ki-ketsu-sui scores measure six factors : qi deficiency (kikyo), qi stagnation (kiutsu), qi counterflow (kigyaku), blood deficiency (kekkyo), blood stasis (oketsu), and fluid retention (suitai). As a result of multi­variate analysis, neurological degenerative disorders had large weight of blood deficiency, fluid retention and qi stagnation. Their adjusted odds ratios (95% confidence interval) were 3.02 (1.43-­6.48), 2.37 (1.13-­5.11), 2.33 (1.01-­5.44), respectively. Most relevant factor to neurological degenerative disorders was a blood defi­ciency. Taking into consideration a prescription of “shimotsuto rui” may contribute to alleviate patient's suf­fering. In addition to subjective symptoms, we need an oriental medicine scale such as pulse, tongue, and ab­dominal examinations to judge a therapeutic effect of Kampo medicine.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. Methods: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. Results: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). Conclusions Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

We evaluated body constituent patterns of 130 consecutive patients with symptomatic acute cerebral infarction. They comprise lacunar infarction (n = 47), atherothrombotic infarction (n = 70), cardiogenic embolism (n = 11), and other type of infarction (n = 2). We compared body constituent patterns between them and 93 consecutive patients with other neurological diseases of the same age. We used qi-ketsu-sui scores to evaluate body constituent patterns in all cases. Qi-ketsu-sui scores measure six factors : qi deficiency (kikyo), qi stagnation (kiutsu), qi counterflow (kigyaku), blood deficiency (kekkyo), blood stasis (oketsu), and fluid retention (suitai). As a result of multivariate model analysis, symptomatic acute cerebral infarction had the largest weight of blood stasis and an adjusted odds ratio (95% confidence interval) was 4.6 (2.45-8.91). Even when gender as a confounding factor was adjusted by stratified analysis, adjusted odds ratios of blood stasis (95% confidence interval) were 7.46 (3.02-20.25) for males and 2.63 (1.02-7.11) for females, and those were maximum. The point (median, interquartile range) of blood stasis was more severe in acute cerebral infarction (24 points, 18-33 points) than other neurological diseases (16 points, 9-23 points). We examined relationships between body constituent patterns and clinical disease type, severity at hospitalization, and sex in patients with symptomatic acute cerebral infarction. Ratio of blood stasis was the largest in any clinical disease type, severity and sex. Blood stasis seemed to be the most important factor in symptomatic acute cerebral infarction.