Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda: results from a non-randomized controlled trial

ABSTRACT: BACKGROUND: While the HIV epidemic is levelling off in sub-Saharan Africa, it remains at an unacceptably high level. Young people aged 15-24 years remain particularly vulnerable, resulting in a regional HIV prevalence of 1.4% in young men and 3.3% in young women. This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda on young people's sexual behavior, HIV knowledge and attitudes. METHODS: In a non-randomized longitudinal controlled trial, fourteen schools were selected in two neighboring districts: Bugesera (intervention) and Rwamagana (control). Students (n = 1950) in eight intervention and six control schools participated in three surveys (baseline, six and twelve months in the intervention). Analysis was done using linear and logistic regression using generalized estimation equations adjusted for propensity score. RESULTS: The overall retention rate was 72%. Time trends in sexual risk behavior (being sexually active, sex in last six months, condom use at last sex) were not significantly different in students from intervention and control schools, nor was the intervention associated with increased knowledge, perceived severity or perceived susceptibility. It did significantly reduce reported stigma. CONCLUSIONS: Analyzing this and other interventions, we identified several reasons for the observed limited effectiveness of peer education: 1) intervention activities (spreading information) are not tuned to objectives (changing behavior); 2) young people prefer receiving HIV information from other sources than peers; 3) outcome indicators are not adequate and the context of the relationship in which sex occurs. Effectiveness of peer education may increase through integration in holistic interventions and redefining peer educators' role as focal points for sensitization and referral to experts and services. Finally, we argue that a narrow focus on sexual risks will never significantly turn the tide.     

Time in bed,sleep quality and associations with cardiometabolic markers in children: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study

We investigated associations of time in bed and multiple sleep quality characteristics with cardiometabolic markers in children. Data from the prevention and incidence of asthma and mite allergy study, a population‐based prospective birth‐cohort study started in 1996–1997 in the Netherlands, were analysed. In total 1481 children aged 11–12 years completed a questionnaire (including questions on sleep) and underwent a medical examination. We measured body mass index, waist circumference, total‐ and high‐density lipoprotein cholesterol, blood pressure and glycated haemoglobin. Results showed that in girls, some sleep characteristics were related to anthropometrics (body mass index, waist circumference) and cholesterol. Girls who had a long time in bed (11–12.5 h) had 0.16 lower body mass index z‐score (95% confidence interval ?0.31; ?0.01) and 0.99 cm smaller waist circumference (95% confidence interval ?2.01; ?0.13) compared with girls who spent 10–10.5 h in bed. Girls who went to bed late and rose early had 0.16 mm higher total cholesterol (95% confidence interval 0.01; 0.31) and 0.08 mm higher high‐density lipoprotein cholesterol (95% confidence interval 0.01; 0.14) than ‘early to bed/early rise’ girls. Girls with night‐time awakenings had 0.14 mm higher total cholesterol (95% confidence interval 0.03; 0.25) than girls without night‐time awakenings. Girls who felt sleepy/tired ≥1 day per week had 0.10 mm lower high‐density lipoprotein cholesterol (95% confidence interval ?0.16; ?0.04) and 0.17 mm higher total cholesterol/high‐density lipoprotein cholesterol ratio (95% confidence interval 0.02; 0.32) than girls who did not feel sleepy. No associations were found for boys. Sleep characteristics were not related to blood pressure and glycated haemoglobin, and effect sizes of the associations in girls were small. Therefore, we consider it premature to propose that improved sleep could reduce cardiovascular risk during childhood.     

Detection of proarrhythmia in the female rabbit heart: blinded validation

INTRODUCTION: Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study. METHODS AND RESULTS: In 142 female rabbits, the monophasic action potential was used to determine intraventricular conduction, action potential duration (APD), triangulation (APD30 to APD90), reverse use-dependence, instability and presence of chaotic behavior, early afterdepolarizations, torsades de pointes (TdP), and ventricular fibrillation. In addition, 31 coded drugs were tested in a blinded fashion in another 150 hearts. Prototype cardiovascular agents [quinidine (IA), lidocaine (IB), flecainide (IC), propranolol (II), sotalol (IIIB), amiodarone (IIIAB) and verapamil (IV)] were correctly characterized in terms of their effects upon conduction and APD. Agents documented in clinical practice to have proarrhythmic potential (droperidol, sotalol, mibefradil, bepridil, lidoflazine, ketanserin, sertindole, terfenadine, haloperidol, astemizole, cisapride, ziprasidone, lubeluzole, dofetilide, quinidine, ibutilide) were identified as such. Pimozide is reported to rarely produce TdP and was also found to elicit Class III action with few adverse effects. Equally important, agents believed not to be proarrhythmic (two solvents, atenolol, propranolol, fenoximone, cetirizine, verapamil, sildenafil, lidocaine, diltiazem) were identified as having no proarrhythmic activity. CONCLUSION: The SCREENIT method properly characterized and quantified prototype cardiovascular drugs and correctly identified proarrhythmic noncardiovascular agents of various mechanisms, but it did not produce false-positive results.     

Comparison of intracranial pressure measured in the cerebral cortex and the cerebellum of the rat

In this study, we evaluated the accuracy of intracranial pressure (ICP) measurement in rats by insertion of a miniature ICP probe in the parenchyma of the cerebellum. A comparison was made between the ICP values measured simultaneously in the parenchyma of the cerebral cortex and the cerebellum. In order to obtain a wide range of ICP, animals were subjected to a severe closed head injury (CHI), a moderate CHI or to a sham operation. ICP values ranged from 0.8 to 43.9 mmHg. After 15 min stabilisation the first measurement was taken and followed by a second measurement 25 min after onset to allow comparison of ICP changes at the two implantation sites. Linear regression analysis showed a highly significant correlation at 15 min: Y = 0.919X + 0.655 (R(2) = 0.977), and at 25 min: Y = 0.931X + 0.698 (R(2) = 0.976). The differences in ICP measurement between cerebellar and cerebral site were not significantly different from zero at both time points. Altman-Bland plots showed that the difference in ICP readings between the two locations could differ maximally by 5.3 mmHg. The largest differences were detected when high ICP values were recorded. We conclude that in rats the ICP measurement in the cerebellum is comparable to the ICP measurement in the cerebral cortex. The cerebellar ICP can be used as a valuable alternative during experimental procedures.     

Pentobarbital fails to reduce cerebral oxygen consumption early after non-hemorrhagic closed head injury in rats

It is unknown whether barbiturates suppress cerebral oxygen metabolism after cerebral trauma as they do in normal individuals. We evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-hemorrhagic closed head injury (CHI). Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidized cytochrome oxidase concentration. CHI caused changes in both systemic and cerebral hemodynamics. Cerebral blood flow was reduced to 66% of its control value, but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a further decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function in traumatized rats, whereas it exerted this effect in all control animals. We therefore conclude that, in rats subjected to CHI, pentobarbital is unable to perform its beneficial effects on the cerebral metabolism.     

Knowledge and opinions of surgical patients regarding nosocomial infections

Sixty-five inpatients in various surgery departments were questioned about their knowledge and opinions regarding nosocomial infection, the information they were given on nosocomial infection, and their supposed attitude should they contract a nosocomial infection. RESULTS: Seventeen (26%, [16-39%]) were able to describe nosocomial infections as infections acquired in hospital. Identification of nosocomial infections as hospital-acquired infections was significantly associated with a high educational level and with having a member of their own family working in a health-related field. Fifty-two patients (80.0%, [68.2-88.9%]) stated that during their hospitalization they had received no information concerning nosocomial infections and 50 patients (76.9% [64.8-86.5]) mentioned that patients would welcome information about nosocomial infections. Thirty-three patients [50.8, 95% CI(38.6-62.9%)] declared that they would seek legal action against the hospital should they contract a nosocomial infection. There was a trend toward a higher probability of legal action in patients who rated their own risk of nosocomial infection as low or absent versus those who rated their own risk of nosocomial infection as medium or high (58.0% vs. 28.6%, p=0.051). The intention of seeking legal action against the hospital in case of nosocomial infection was not significantly influenced by patients' opinion regarding nosocomial infection preventability.     

Who would suffer this child in the cold? History and diagnosis during a Socratic dialogue

This article gives an account of the experiences of 12 dentists (11 general practitioners and one periodontist) during a one-day Socratic dialogue, which took place at the International Conference for Dentists in Bruges 2001. The key question was: "When must I (or mustn't I) comply with the patient's wish?" The participants tackled an example from Edgar, general practitioner. His story went like this: on Christmas Eve, dinnertime, one of his patients--duly instructed beforehand--arrived just like that, and said: "I'm in pain". When the central question was applied to this example, uncertainty arose about the exact nature of "the patient's wish". In this article you read how the participants dealt with the "pain", with the uncertainty.