上肢力量训练对脑卒中患者上肢及手指功能恢复和卒中后抑郁的影响

目的：观察脑卒中患者上肢力量训练对上肢及手指功能恢复的影响,并评价其对脑卒中后抑郁缓解的效果。方法：选取2017年1月至2017年5月于同济大学医学院附属第十人民医院收治的首次发病脑卒中合并偏瘫患者100例作为研究对象。患者随机分为2组（n=50）：对照组给予常规康复治疗,卒中后抑郁患者加用盐酸帕罗西汀治疗;训练组在常规康复治疗的基础上,给予力量训练,卒中后抑郁患者加用盐酸帕罗西汀治疗。所有患者在治疗前、治疗后6个月均采用Fugl-Meyer量表（FMA）、Barthel指数（BI）和美国国立卫生研究院脑卒中量表（NIHSS）进行评定;卒中后抑郁患者采用汉密顿抑郁量表（HAMD）进行抑郁程度评价。结果：治疗6个月后,训练组患者FMA、FMA（上肢）、FMA（手指）和NIHSS评分均高于对照组,差异有统计学意义（P<0.05）;两组间Barthel指数差异无统计学意义。两组卒中后抑郁患者治疗6个月后,训练组患者HAMD评分优于对照组（P<0.05）。结论：脑卒中患者上肢力量训练能改善上肢及手指功能,有效提高患者生活质量,且有助于缓解卒中后抑郁。     

Accuracy of administrative claims data to identify dose specific rotavirus vaccination information: Implications for studies of vaccine safety

BackgroundThe accuracy of vaccine administration information recorded in administrative claims databases is uncertain.MethodsWe conducted a retrospective cohort study using the HealthCore Integrated Research Database^SM among infants who received at least 1 RotaTeq^® (RV5) dose during the first year of life between February 1, 2006 and November 30, 2012 and were enrolled in the health plan at birth. We reviewed medical records for a sample of infants to validate vaccine administration information.ResultsWe identified 169,560 infants who received at least 1 RV5 dose. Medical records were obtained for 85 infants, of which 74 (PPV1 87.1%; 95% CI 78.0–93.4%) had a corresponding first RV5 vaccination in the medical record with the same or similar administration date.ConclusionsAdministrative claims contained inaccuracies in dose number or administration date for 13% of RV5 first doses identified.     

Bayesian dose‐finding designs for combination of molecularly targeted agents assuming partial stochastic ordering

Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose‐finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose–efficacy and dose–toxicity models. Motivated by a phase I/II clinical trial of a combination of two MTAs in patients with pancreatic, endometrial, or colorectal cancer, we propose Bayesian dose‐finding designs to identify the OBDCs without parametric model assumptions. The proposed approach is based only on partial stochastic ordering assumptions for the effects of the combined MTAs and uses isotonic regression to estimate partially stochastically ordered marginal posterior distributions of the efficacy and toxicity probabilities. We demonstrate that our proposed method appropriately accounts for the partial ordering constraints, including potential plateaus on the dose–response surfaces, and is computationally efficient. We develop a dose‐combination‐finding algorithm to identify the OBDCs. We use simulations to compare the proposed designs with an alternative design based on Bayesian isotonic regression transformation and a design based on parametric change‐point dose–toxicity and dose–efficacy models and demonstrate desirable operating characteristics of the proposed designs. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.     

A method for systematic discovery of adverse drug events from clinical notes

Objective Adverse drug events (ADEs) are undesired harmful effects resulting from use of a medication, and occur in 30% of hospitalized patients. The authors have developed a data-mining method for systematic, automated detection of ADEs from electronic medical records.Materials and Methods This method uses the text from 9.5 million clinical notes, along with prior knowledge of drug usages and known ADEs, as inputs. These inputs are further processed into statistics used by a discriminative classifier which outputs the probability that a given drug–disorder pair represents a valid ADE association. Putative ADEs identified by the classifier are further filtered for positive support in 2 independent, complementary data sources. The authors evaluate this method by assessing support for the predictions in other curated data sources, including a manually curated, time-indexed reference standard of label change events.Results This method uses a classifier that achieves an area under the curve of 0.94 on a held out test set. The classifier is used on 2 362 950 possible drug–disorder pairs comprised of 1602 unique drugs and 1475 unique disorders for which we had data, resulting in 240 high-confidence, well-supported drug-AE associations. Eighty-seven of them (36%) are supported in at least one of the resources that have information that was not available to the classifier.Conclusion This method demonstrates the feasibility of systematic post-marketing surveillance for ADEs using electronic medical records, a key component of the learning healthcare system.     

Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular remodeling in isoproterenol‐induced postmyocardial infarction

Extracellular matrix (ECM) remodeling is a major pathophysiological process during post‐myocardial infarction (MI). The activation, differentiation, and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signaling by bone morphogenetic protein (BMP‐4), an extracellular ligand of the TGF‐β family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity. The primary aim of the study was to investigate BMP‐4‐mediated ECM turnover in cardiac fibrosis during isoproterenol‐induced post‐MI and its downregulation by OPC. Myocardial injury was evaluated by assaying serum markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic antioxidant levels were assessed to support the cardioprotective nature of OPC. The total collagen level was analyzed by measuring hydroxyproline levels. The ISO‐induced group showed a significant decrease in the levels of antioxidants due to severe oxidative stress and increased expression of BMP‐4 which reflects the increased expression of MMP 2 and 9 with a concomitant increase and deposition of fibrillary collagens type I and III responsible for the fibrotic scar formation as evidenced in the histological analysis.BMP‐4 activation, thus, is strongly associated with cardiac fibrosis which was downregulated upon OPC supplementation. This study provides an evidence supporting the antifibrotic effect of OPC via regulation of BMP‐4‐mediated ECM turnover and also substantiates the remarkable antioxidant efficacy of OPC against isoproterenol induced severe oxidative stress and subsequent post‐MI cardiac fibrosis.     

Benefits and risks of immediately sequential bilateral cataract surgery: a literature review

Immediately sequential bilateral cataract surgery (ISBCS) is a highly contended issue in ophthalmology, mainly due to the risk of bilateral endophthalmitis and financial penalties that many ophthalmologists face when performing simultaneous cataract surgeries. The purpose of this review is to understand the current status of the knowledge of ISBCS, mainly its benefits and risks and how they compare with the standard of care, delayed sequential bilateral cataract surgery. Evidence, although limited, increasingly supports ISBCS for providing faster rehabilitation, improved visual outcomes, and cost and time savings. Evidence does not support the fear of bilateral endophthalmitis resulting from the simultaneous procedure. However, stronger and greater evidence is needed before ISBCSs can be considered the standard of care. Where ISBCS can potentially create the most beneficial impact is in public eye health programmes in developing countries, but this has not yet been explored.     

CaMKIIδ and cardiomyocyte Ca2+ signalling new perspectives on splice variant targeting

Control of cardiomyocyte cytosolic Ca²⁺ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca²⁺, Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca²⁺ channels/transporters. CaMKII is primarily expressed either in the δ_B or δ_C splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca²⁺ levels promote the binding of a Ca²⁺/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδ_B/δ_C variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca²⁺ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδ_B in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδ_C. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδ_B, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca²⁺ uptake and maintain cytosolic Ca²⁺ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.     

The role of apheresis therapy in living donor liver transplantation

Liver transplantation is a radical therapy for end-stage liver disease. The severe shortage of transplantable organs is, however, a big problem, not only in liver transplantation but also other organ transplants. Although in Japan, transplantation of organs obtained from brain-dead donors (BDD) has been allowed since October 1997, to date only 27 BDD have been obtained. It has become difficult to procure liver grafts from BDD, therefore we must use liver grafts from living donors. The living-donor liver transplantation (LDLT) program started in 1990 in Japan, and is still the major form of liver transplantation because of the scarcity of cadaveric donors. In the Department of Transplant Surgery, Kyoto Hospital (Kyoto, Japan), the accumulated number of LDLT cases exceeded 955 up to October 2003. In order to perform LDLT under safer conditions, apheresis plays a major role in Japan due to the prevalence of LDLT where later retransplantation is difficult. Clinical indications of apheresis for LDLT are mainly use as a bridge before transplantation, and liver support after transplantation. We describe the effect of apheresis therapy for LDLT patients with nephritic and hepatic problems.     

Perioperative safety and short-term efficacy of functional minimally invasive esophagectomy

BackgroundStandard minimally invasive McKeown three-field esophagectomy (SMIE) results in high perioperative risk and poor postoperative quality of life owing to considerable surgical damage and numerous postoperative complications. We created a modified procedure, functional minimally invasive esophagectomy (FMIE), which preserves the azygos arch, bronchial artery, pulmonary branch of the vagus nerve, and the mediastinal pleura. Our aim was to evaluate the efficacy and safety of FMIE and to determine whether it has limited invasiveness.MethodsBetween 2018 and 2020, FMIE was performed for 48 patients who were compared with 76 SMIE cases; 44 paired cases were matched using propensity score matching.ResultsOperation time, extubation time, and postoperative hospital stay were significantly lower in the FMIE group. FMIE was also associated with fewer pulmonary infections. Postoperative drainage volume on postoperative day (POD) 1 and POD 2, and white blood cell counts on POD 2 and POD 4 were also significantly lower in the FMIE group. There was no statistically significant difference in the number of dissected lymph nodes, short-term recurrence, metastasis rates, or survival rate between the two groups.ConclusionsFMIE is a less invasive procedure and may be a suitable alternative for lower and early middle esophageal carcinoma.