Appropriateness in health care delivery: definitions, measurement and policy implications.

A major focus of the current health care debate is the notion that a substantial proportion of the health care delivered in Canada is inappropriate. There are two types of appropriateness: appropriateness of a service and appropriateness of the setting in which care is provided (i.e., inpatient v. outpatient or home care). Measuring both types objectively requires the comparison of observed patterns of care with explicit criteria for appropriate care. The few studies of appropriateness conducted in Canada have shown that inappropriate services are provided and inappropriate settings are used. Reducing inappropriate health care delivery could involve active strategies for the implementation of guidelines and better cooperation and coordination within the health care system. However, lower rates of health care delivery or even inappropriate health care will not necessarily translate into higher quality care or lower costs overall.     

Messenger molecules and cell death: therapeutic implications

Thomas W. Sedlak, MD, PhD; Solomon H. Snyder, MD

JAMA. 2006;295:81-89.

Programmed cell death, also called apoptosis, participates not only in normal physiologic processes such as development of the immune system, but also in many diseases. A loss of normal cell death may occur in cancer, and excessive cell death is found in a variety of neurodegenerative conditions. We describe 3 distinct pathways that regulate cell death. First, bilirubin, often thought to be a toxic end product of heme metabolism, serves as a physiologic cytoprotectant that may attenuate multiple forms of morbidity. In a second pathway, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mediates a novel cell death cascade. Cytotoxic stimuli, via nitric oxide generation, lead to the binding of GAPDH to the protein Siah1, translocation of GAPDH-Siah1 to the nucleus, and ultimately cell death. Third, cytochrome c, released from mitochondria early in apoptosis, synergizes with inositol-1,4,5-triphosphate (IP3) to elicit massive cellular calcium release, resulting in cell death. These pathways may regulate cell survival in a variety of pathologic states and represent fertile targets for novel therapies.

     

Mixed dementia: emerging concepts and therapeutic implications

Context  The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages. Objectives  To provide an overview of the diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia. Data Sources, Study Selection, and Data Extraction  The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy. Evidence Synthesis  Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups’ scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia. Conclusions  Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.      

Diversity of blood pressure recording during pregnancy: implications for the hypertensive disorders.

OBJECTIVE: To determine the number and type of methods used to measure blood pressure (BP) in pregnant women. DESIGN: Questionnaires were distributed to obstetricians and midwives concerning: method of recording BP (arm used, subject position, Korotkoff sounds recorded); accuracy of recording BP (cuff size, sphygmomanometer calibration); and definitions of hypertension in pregnancy. PARTICIPANTS: Obstetricians (academic, staff and private) in Sydney; members of the New South Wales Midwives' Association. MAIN RESULTS: Responses were received from 85 obstetricians (55% of those surveyed) and 173 midwives (43%); the overall response rate was 46%. Almost 80% of respondents agreed that diastolic BP above 90 mmHg constituted hypertension during pregnancy but at least six different methods were used to obtain BP readings, with a potentially large variability in the BP so obtained. Forty-five per cent of obstetricians and 72% of midwives stated that they always used a large cuff when necessary. Few had had their sphygmomanometer calibrated within the previous two years. CONCLUSIONS: There is considerable variability in the way BP is recorded in pregnant women. Hypertension in pregnancy may therefore be over or under diagnosed according to the method employed and there is an urgent need for international consensus on how to measure BP accurately in pregnancy.     

Jaccoud's arthropathy--diagnostic and therapeutic implications

A case of isolated chronic severe aortic regurgitation with Jaccoud's arthropathy involving the foot is presented. The interesting feature of the case is the absence of history of acute rheumatic arthritis at any stage of the illness. The diagnostic and possible therapeutic significance of this otherwise uncommon and benign condition are discussed.     

天疱疮的合理治疗及预后影响因素分析

目的：探讨天疱疮的合理治疗方案,分析其预后及影响因素。方法：48例天疱疮患者中寻常型(PV)35例、红斑型(PE)5例、落叶型(PF)3例、增殖型1例、疱疹样天疱疮(HP)4例。按患者意愿分为糖皮质激素组34例、糖皮质激素＋免疫抑制剂组14例,观察糖皮质激素用量、治疗效果、不良反应及影响预后的因素。结果：糖皮质激素组的激素最大控制剂量、控制疾病所需激素总量高于糖皮质激素＋免疫抑制剂组（P<0.05）。重症患者的糖皮质激素初始量、糖皮质激素最大控制量及控制总量高于中症患者（P<0.05及P＜0.01）。重症、60岁以上、皮肤和黏膜同时受累患者的病死率分别高于中症、60岁以下、仅有皮肤损害者（P＜0.05）。结论：天疱疮病情轻重是确定糖皮质激素用量的重要因素。糖皮质激素联合免疫抑制剂疗效更佳,高龄、有黏膜损害的重症天疱疮患者预后不良。     

Hepatitis C virus genotypes: clinical relevance and therapeutic implications

The incidence of hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) has been increasing in several countries including Taiwan. There are six main genotypes, each of which contains closely related subtypes. Molecular epidemiological studies have shown marked differences in the genotype distribution by geographical region and between patient groups. HCV genotype 1 may play a role in the development of HCC, although some studies have argued against this. A sustained virological response secondary to interferon monotherapy or interferon/ribavirin combination therapy may reduce the risk of HCC and improve survival in chronic hepatitis C patients. The HCV genotypes are associated with therapeutic response. Rapid virological response is also a predictor of therapeutic response. Although viral characteristics have consistently been shown to be important predictors of treatment response, identification of additional host immune and genetic factors involved in determining the outcome of antiviral therapy is necessary. Newly developed bio-techniques (microarray, proteomes, bioinformatics), drugs, and treatment strategies may elucidate the pathogenesis and improve the therapeutic response in HCV infection.     

高血压与血脂、同型半胱氨酸关系的研究

目的：探讨高血压与血脂、同型半胱氨酸的关系。方法：选取高血压患者及血压正常人群各250例,并对高血压患者进行分级;所有患者于早上抽取空腹静脉血测定三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、同型半胱氨酸（Hcy）。结果：高血压组和正常对照组比较,TG、Hcy、TC和LDL-C差异有高度统计学意义（P〈0.01）,HDL-C无明显差异。TG、TC、LDL-C、Hcy均随着血压的升高而升高,HDL-C随着血压的升高而逐步降低;男性高血压组比女性高血压比较,TG和Hcy差异有高度统计学意义（P〈0.01）,TC、HDL-C和LDL-C无差异。结论：高血压与血脂、Hcy存在密切的相关性,加强心血管健康保健知识和干预措施教育,促使人民自觉地采纳有益健康的行为和生活方式,对于消除或减轻影响健康的危险因素,预防疾病,促进健康和提高生活质量具有重要意义。     

Average daily blood pressure, not office blood pressure, determines cardiac function in patients with hypertension

To determine the presence of cardiac disease in hypertensive patients with disparities between physician and out-of-office blood pressures, we prospectively studied three groups of age-matched patients identified by both casual (office) and ambulatory blood pressures: (1) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less ("office" hypertensives); (2) office blood pressure less than 135/85 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less (normotensives); and (3) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 140/90 mm Hg or greater ("daytime" hypertensives). In the patients with office hypertension, both the left atrial index and left ventricular mass index were significantly less than in patients with daytime hypertension and not statistically different from those of the normotensive subjects. Left ventricular filling rate at rest and ejection fraction at peak exercise were significantly greater in the office hypertensive group than in the daytime hypertensive group but were no different from those of the normotensive subjects. These findings demonstrate that patients with blood pressure elevation only in the physician's office have cardiac size and function similar to those of normotensive individuals. Thus, the average daily blood pressure best predicts cardiac end-organ damage.