Hepatopulmonary syndrome

The hepatopulmonary syndrome is an increasingly important vascular complication of cirrhosis where microvascular dilatation impairs arterial oxygenation in the setting of liver disease. This syndrome is identified in as many as 20% of patients evaluated for liver transplantation and results in increased mortality. No clearly effective medical therapies are available, and liver transplantation is the only established treatment. Pathophysiologic insights obtained from experimental models may lead to the development of novel and effective medical treatments.     

Regional block and DVT prophylaxis

The last few years have seen increasing concerns among anaesthetistsabout the risks of pharmacological prophylaxis for thromboembolicdisease. Increased bleeding during or after surgery is one concern,but of greater significance is the possibility of an increasedpredisposition to haematoma formation when regional block isused. Most of the recent consideration of this problem has beenin relation to vertebral canal haematoma formation after centralnerve block. Some thought must be given also to the possibilityof haematoma formation after peripheral techniques when thetarget nerve is deeply placed so that pressure cannot be usedto control bleeding after needle insertion. However, this reviewwill be focused on vertebral canal haematoma.     

Cost-effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re-bleeding

BACKGROUND: Measurement of the hepatic venous pressure gradient may identify a sub-optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined. METHODS: A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta-blockers alone, beta-blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta-blockers plus isosorbide mononitrate or beta-blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non-responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years. RESULTS: The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost-effectiveness ratio of the latter strategy was 136,700 dollars per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re-bleeding were increased. CONCLUSIONS: The cost-effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re-bleeding rates.     

Open label, multicenter study of gatifloxacin treatment of recurrent otitis media and acute otitis media treatment failure

BACKGROUND: Recurrent otitis media and treatment failures of acute infections are refractory to therapy. Newer fluoroquinolones have excellent activity against respiratory pathogens, but their use in children has been limited because of concerns about adverse effects. METHODS: This was an open label, multicenter trial in which patients with recurrent otitis media or acute otitis media (AOM) treatment failure were treated with 10 mg/kg gatifloxacin oral suspension once daily for 10 days. Before treatment a tympanocentesis or a swab of middle ear fluid was obtained. Nasopharyngeal swabs were obtained at baseline and at the end of therapy. Efficacy was evaluated 3 to 10 days after cessation of treatment and at 3 to 4 weeks. Safety monitoring included special attention to any sign or symptom suggestive of joint or bone abnormality. RESULTS: The study enrolled 254 patients 6 months to 7 years of age, with one-half (52%) of the patients having recurrent otitis media, 17% having AOM treatment failure and 28% having both. Cure was achieved posttreatment in 88% of 198 clinically evaluable patients, with similar outcomes for patients younger or older than 2 years of age. Of the 45 evaluable patients with Streptococcus pneumoniae, 38 (84%) were cured, including 25 of 28 with penicillin-nonsusceptible strains. Also cured were 89% of those with Haemophilus influenzae and those with Moraxella catarrhalis. No selection of resistance to gatifloxacin was detected among nasopharyngeal pathogens. Eighty-three percent of the children had sustained cure at the 4 weeks follow-up visit. Adverse events were primarily mild gastrointestinal, with no occurrences of arthropathy. CONCLUSION: Gatifloxacin is safe and effective for treatment of recurrent otitis media and AOM treatment failure in children.     

High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.     

Surveillance colonoscopy or chemoprevention with COX-2 inhibitors in average-risk post-polypectomy patients: a decision analysis

OBJECTIVES: Clinical trials are currently underway evaluating the efficacy of COX-2 inhibitors in decreasing the incidence of adenomas and colorectal carcinoma in 'average' risk individuals. AIM: To use decision analysis to compare the cost-effectiveness of celecoxib to surveillance colonoscopy in 'average' risk patients who had undergone prior adenoma resection. METHODS: A model of the natural history of adenomas after endoscopic polypectomy was constructed using probabilities from the literature. Cost estimates were obtained from available Medicare reimbursement rates and supplemented by the literature. Three strategies were evaluated: (i) no surveillance; (ii) colonoscopic surveillance; and (iii) celecoxib chemoprevention. We compared total costs and performed cost-effectiveness analysis between these strategies. The outcome measures were years of life saved and 'high-grade' adenoma prevented. Sensitivity analyses were performed on selected variables. RESULTS: Our base-case analysis assumed a 50% risk reduction in the incidence of adenomas among patients using celecoxib. No surveillance was associated with a cost of $1014 per patient, and colonoscopic surveillance with a cost of $1572 per patient, whereas celecoxib use was associated with a total cost of $11,503. Ten years after the index colonoscopy, 15% of patients in the no surveillance strategy developed 'high-grade' lesions compared to 13% of patients in the colonoscopic surveillance group and 6% in the celecoxib group. There was a small gain in years of life saved (0.006) favouring celecoxib over colonoscopic surveillance. The incremental cost-effectiveness ratio of celecoxib vs. colonoscopy was $141 871 per 'high-grade' adenoma prevented and $1,715,199 per year of life saved. The most important variables in determining the cost-effectiveness of celecoxib were its cost and its efficacy. CONCLUSION: Chemoprevention with COX-2 inhibitors in 'average-risk' postpolypectomy patients is a more expensive strategy compared to colonoscopic surveillance.     

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

口服Carvedilol治疗心力衰竭多中心研究(MOCHA)

标题　Ｃａｒｖｅｄｉｌｏｌ对慢性心力衰竭患者左心室功能的改善和存活的提高呈剂量相关性作者　ＢｒｉｓｔｏｗＭＲ，ＧｉｌｂｅｒｔＥＭ，ＡｂｒａｈａｍＷＴ，等　　Ｃｉｒｃｕｌａｔｉｏｎ１９９６，９４：２８０７～２８１６　　研究疾病：充血性心力衰竭。目的：对Ｃａｒｖｅｄｉｌｏｌ治疗慢性心力衰竭患者剂量－疗效特征进行评价。　　设计：随机、双盲、安慰剂对照的多中心研究，剂量效应关系研究。病人资料：共３４５名心力衰竭患者，年龄１８～８５岁，左室射血分数≤０－３５，心力衰竭症状时间≥３月，研究前所有患者必须用利…