Can Electrocardiographic Criteria Predict Adverse Cardiac Events and Positive Cardiac Markers?

OBJECTIVES: To determine electrocardiogram (ECG) predictors of positive cardiac markers and short-term adverse cardiac events in an undifferentiated chest pain population presenting to emergency departments (EDs). The authors hypothesized that specific ECG findings, other than those previously identified in higher-risk populations, would be predictive of cardiac outcomes and positive cardiac markers. METHODS: This study used data from a prospectively collected, retrospectively analyzed Internet-based data registry of undifferentiated chest pain patients (i*trACS). Logistic regression modeling was performed to determine the ECG findings that were predictive of 1) positive cardiac markers and 2) short-term adverse cardiac events. RESULTS: ST-segment elevation (STE), ST-segment depression (STD), pathological Q-waves (PQW), and T-wave inversion were associated with increased odds of percutaneous coronary intervention or catheterization, myocardial infarction, or coronary artery bypass grafting. The odds of creatine kinase-MB (CK-MB) measuring positive were increased if STE, STD, or PQW were present [odds ratio (OR) 2.495, 2.582, and 1.295, respectively]. A right bundle branch block tended to decrease the odds of CK-MB measuring positive (OR 0.658). A similar pattern of results was observed for troponin I (OR 3.608 for STE, 3.72 for STD, 1.538 for PQW). Troponin T showed an increased odds of measuring positive if any of STE, STD, left bundle branch block, or T-wave inversion were evident (OR 2.313, 2.816, 1.80, and 1.449, respectively). CONCLUSIONS: Initial ECG criteria can be used to predict short-term cardiac outcomes and positive cardiac markers. These findings can be important aids in the risk-stratification and aggressive treatment regimens of chest pain patients presenting to EDs.     

奥利司他对肥胖青少年体重和机体组分的影响——随机对照试验

背景：儿童和青少年超重和肥胖正迅速增加。在该人群，单纯行为疗法减肥及维持体重下降的效果有限，但是对药物治疗尚未进行广泛的研究。 目的：确定奥利州他（Orlistat）在青少年体重治疗方面的效果及其安个性。 设计、地点和病例：于美国和加拿大32个中心、539例肥胖青少年（12—16岁；体重指数[body mass index，BMI]在第95百分化之上≥2单位）进行的多ln0、54剧（2000年8月至2002年10月）随机双盲研究。 干预：给予奥利司他（n=357）或安慰剂（n=182）120mg，每口3次，持续1年；加适度低热卡饮食（脂肪占30％）、运动和行为治疗。 主要观察指标：BMI变化；二级指标包括腰围和髋用、体重下降、脂质测量以及机体对口服葡萄糖的血糖和胰岛素反心。 结果：至12周时，两组BMI均有下降；此后，奥利司他组体重维持稳定而安慰剂组则超过基线。研究结束时，奥利司他组BMI下降0．55。而安慰剂组则增加0．31（P=0．001）。与安慰剂组的15．7％相比，奥利司他组26．5％的病例BMI下降≥5％（P=0．005）；BMI下降≥10％者分别为4．5％和13．3％（P=0．002）。在研究结束时，奥利司他组体重增加0．53kg，安慰剂组增加3．14kg（P〈0．001）。双能X线吸收测量娃示，这种差异可用脂肪体再的变化解释。奥利司他组腰围下降，安慰剂组腰围上升（-1．33cm比＋0．12cm；P〈0．05）。奥利司他组发生轻至中度胃肠道不良事件者为9％-50％，安慰剂组为1％～13％。 结论：与安慰剂比较，奥利司他与饮食、运动和行为改善联合可显著改善肥胖青少年体重的治疗。在这个青少年人群，连续使用奥利司他1年并无重要安全问题，尽管奥利司他组胃肠道不良事件较为常见。     

Inhibition of post-meningitic cochlear injury with cerebrospinal fluid irrigation.

OBJECTIVE: Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profound deafness and loss of vestibular function occurs frequently as a sequella of bacterial meningitis and subsequent purulent labyrinthitis. Experimentally, in Streptococcus pneumoniae meningitis, it has been shown that a vigorous inflammatory response to teichoic acids in the bacterial cell wall contributes to cochlear damage and subsequent fibrosis and ossification. The hypothesis of this study is that a dilution of concentration of inflammatory mediators through cerebrospinal fluid (CSF) irrigation will lead to a reduction in both inner ear pathology and permanent hearing loss. STUDY DESIGN AND SETTING: Auditory brainstem response testing was used to determine baseline hearing thresholds in 20 Mongolian gerbils (12 irrigated, 8 sham irrigated animals) at 32 kHz, 16 kHz, 8 kHz, and 4 kHz frequencies. Their thresholds at 14 days and 120 days post-procedure were also obtained. Streptococcus pneumoniae meningitis was induced in both groups of animals by intrathecal (i.t.) injection of bacteria. Both groups received penicillin treatment. Forty-eight hours after inoculation, both groups were implanted with i.t. inflow and outflow catheters. The irrigated group was infused continuously with artificial CSF over 36 hr at a rate of 70 muL/hr and the outflow sampled. The tubing in the sham irrigated group was clamped (without sampling). They were sacrificed at 120 days post-procedure and histomorphometric analysis carried out. The concentration of interleukin 1beta (IL-1beta) for the CSF samples from the irrigated group were compared to samples collected from an additional control group of 8 non-irrigated meningitic gerbils. IL-1beta was chosen to study because it is a potent pro-inflammatory cytokines in bacterial meningitis that is unaffected by the neurosurgical trauma of the experimental protocol. RESULTS: Twenty animals survived the meningitis (6 irrigation, 6 sham irrigation, 8 non-irrigation meningitic controls). At Days 14 and 120 post-infection, the irrigated animals manifested significantly less hearing loss with a mean loss of 28.82 dB compared to the sham irrigation group mean loss of 40.76 dB (P < 0.03). The degree of hearing loss in both groups was frequency-dependent with greater loss at higher frequencies (mean loss = 22.4 dB at 32 kHz, 23.0 dB at 16 kHz, 18.6 dB at 8 kHz, and 12.5 dB at 4 kHz). Histomorphometric analysis demonstrated a marked reduction in degeneration of the spiral ligament, spiral ganglion cells, and stria vascularis in experimental animals as compared to controls. Immunohistochemistry showed a significant reduction in IL-beta1 concentrations in the irrigated animals compared to the non-irrigated, infected controls (P < 0.03). CONCLUSIONS: Irrigation of CSF resulted in a significant reduction in post-meningitic cochlear injury when compared to controls. This model for continuous cerebrospinal fluid irrigation provides a means to evaluate the effects of a dilution of inflammatory mediators on hearing loss and labyrinthitis ossificans after bacterial meningitis. SIGNIFICANCE: Despite advances in the prevention of meningitis and improved antibiotic treatment, bacterial meningitis continues to have significant associated morbidity. This study provides insight into some of the mechanisms responsible for post-meningitic hearing loss and labyrinthitis ossificans and presents a novel approach to reduce these complications.     

Measuring the efficacy of antiepileptic drugs.

Clinical trials of new antiepileptic drugs (AEDs) include regulatory studies aimed at demonstrating efficacy and reasonable safety, post-marketing open-open label studies and longer term outcome studies. Regulatory trials involve a carefully selected population of patients and are conducted under rigorously standardised conditions. Data from such studies cannot often be translated into clinical practice. Pragmatic post-marketing studies using flexible dosing schedules allow clinicians to better judge the utility of the new drug in a wider population of patients with epilepsy and decide the most appropriate dosing schedules. This paper discusses some of the issues surrounding the measurement of efficacy of new AEDs in both pre- and post-marketing phases of their development. All of the newer AEDs are initially used in patients with refractory partial seizures as adjunctive treatment. These trials are generally parallel-group studies although cross-over designs have been employed. The use of placebo-control is uncontroversial in this type of study. Efficacy endpoints are generally manipulations of seizure frequency on study drug compared to control. Global outcome measures and health related quality of life scores can also be used to measure efficacy. As the standard AEDs are associated with a high rate of seizure remission in patients who receive them as monotherapy, demonstration of superior efficacy of a new agent in a comparative trial will require large numbers of patients in a design that takes into account the natural history of treated epilepsy. Comparing investigational agents to a standard AED in an 'active-control' study with demonstration of equivalent efficacy would seem to be an acceptable way of assessing efficacy of new AEDs in this population. Some regulators, however, do not accept equivalence as proof of efficacy and insist on demonstration of superiority compared to a control. The use of placebo alone in the control group is ethically dubious. Several innovative study designs have, therefore, been used to satisfy regulatory requirements, while maintaining patient safety including withdrawal to monotherapy using high versus low dose comparators. Observational outcome studies provide the best opportunity of exploring the long-term utility of individual AEDs. Such studies largely follow standard clinical practice and need considerable time and resources. They can, however, yield valuable information about the effectiveness of AEDs in everyday clinical practice. Data from regulatory trials should be complemented by postmarketing studies and longer term studies of outcome to help clinicians decide the best way of utilising new AEDs and establishing their role in the therapeutic armamentarium.     

Outpatient Initiation of Insulin: A Nurse Practitioner Protocol

Noninsulin dependent diabetes (type II diabetes) is a chronic disease characterized by hyperglycemia. Clients can generally be controlled by diet and exercise or a combination of diet, exercise, and oral hypoglycemic agents. When this therapy is not effective in controlling the hyperglycemia, the health care provider must choose to initiate insulin therapy. Outpatient initiation of insulin is an alternative to hospitalization in the type II diabetic client. Clinical guidelines for the initiation of insulin on an outpatient basis and management of the diabetic client are presented.