Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials

OBJECTIVE: The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV). METHODS: Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo. RESULTS: Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36). CONCLUSIONS: If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.     

Are Canadian Inuit at increased genetic risk for coronary heart disease?

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.     

Intraosseous infusion in an emergency situation: a case report

A patient with a pelvic silicone prosthesis is presented. The sonographic and computed tomographic features in such patients can be confusing and incorrectly interpreted unless the radiologist knows that the prosthesis had been inserted as a radioprotective device.     

Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction

BACKGROUND: Increases in life stress have been linked to poor prognosis, after myocardial infarction (MI). Previous research suggested that a programme of monthly screening for psychological distress, combined with supportive and educational home nursing interventions for distressed patients, may improve post-MI survival among men. Our study assessed this approach for both men and women. We aimed to find out whether the programme would reduce 1-year cardiac mortality for women and men. METHODS: We carried out a randomised, controlled trial of 1376 post-MI patients (903 men, 473 women) assigned to the intervention programme (n = 692) or usual care (n = 684) for 1 year. All patients completed a baseline interview that included assessment of depression and anxiety. Survivors were also interviewed at 1 year. FINDINGS: The programme had no overall survival impact. Preplanned analyses showed higher cardiac (9.4 vs 5.0%, p = 0.064) and all-cause mortality (10.3 vs 5.4%, p = 0.051) among women in the intervention group. There was no evidence of either benefit or harm among men (cardiac mortality 2.4 vs 2.5%, p = 0.94; all-cause mortality 3.1 vs 3.1%, p = 0.93). The programme's impact on depression and anxiety among survivors was small. INTERPRETATION: Our results do not warrant the routine implementation of programmes that involve psychological-distress screening and home nursing intervention for patients recovering from MI. The poorer overall outcome for women, and the possible harmful impact of the intervention on women, underline the need for further research and the inclusion of adequate numbers of women in future post-MI trials.     

Influenza vaccination in 22 developed countries: an update to 1995

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.     

Mechanisms, diagnosis, and treatment of diastolic heart failure

Diastolic heart failure, in the absence of LV systolic dysfunction, is a common clinical condition that can be demonstrated in as many as one third of patients with congestive heart failure. Diastolic dysfunction caused by abnormalities in LV filling can be a result of many pathologic conditions, including hypertrophy, infiltrative cardiomyopathies, or myocardial ischemia. The major physiologic determinants of LV filling can be divided into cellular mechanisms, hemodynamic characteristics, and hormonal influences. Cellular mechanisms for impaired LV inactivation are determined by the handling of calcium within the myocyte during excitation-contraction-relaxation coupling. The hemodynamic characteristics of LV diastolic filling are determined by loading conditions, the time constant of isovolumic relaxation, heart rate, ventricular nonuniformity, pericardial restraint, myocardial elasticity, chamber compliance, and coronary blood flow. The sympathetic nervous system and the renin-angiotensin system are important modulators of diastolic filling, directly or indirectly. The diagnosis of heart failure is confirmed by a combination of clinical tests including invasive and noninvasive techniques, each of which has advantages and disadvantages. Treatment of medical conditions in which diastolic heart failure is a prominent component include pharmacotherapy with calcium channel antagonists, beta-adrenergic blocking agents, diuretic agents, and angiotensin-converting-enzyme inhibitors. Certain conditions associated with diastolic filling abnormalities such as pericardial disease or severe ischemic heart disease may be best managed by surgical or percutaneous intervention. Future research will include further delineation of the cellular mechanisms of active myocardial relaxation and clinical investigation into treatment directed at improving outcome.