Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.

Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.     

Systematic overview of drug interactions with antidepressant medications.

OBJECTIVE: Antidepressants are commonly used drugs with potential for numerous drug interactions. This study aims to systematically review the literature on drug interactions with antidepressants. METHODS: We searched MEDLINE (1966 to November 2003) and EMBASE (1980 to 2003), using the heading drug interactions combined with individual antidepressant names. We restricted searches to English-language articles and human studies. We screened drug interaction texts and review articles for relevant studies. We included articles reporting original human data on drug interactions with antidepressants commonly used in North America. Articles were independently evaluated by 2 reviewers on clinical effect, clinical significance, and quality of evidence. Discrepancies were resolved by consensus. RESULTS: There were 904 eligible interactions, involving 9509 patients, for a total of 598 summary interactions. Of these, 439 (73%) demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting evidence. For 510 interactions (85%), the quality of evidence was poor. It was fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no interactions with excellent quality of evidence. There were 145 (24%) interactions of major clinical significance. These were predominantly hypertensive emergencies and serotonin syndrome. Most interacting drugs had central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors (MAOIs) appear to be the most problematic family in terms of potential for serious drug interactions. CONCLUSIONS: Drug interactions with antidepressants are an important cause for concern, but this concern is based primarily on poor evidence. We recommend caution when combining antidepressants with other CNS drugs, particularly when coadministering MAOIs with other substances.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

The impact of a nurse externship program on the transition process from graduate to registered nurse: Part III. recruitment and retention effects.

This is the third and final part of a series of articles that report the findings of a study that investigated the effects of a summer externship program on the transition into a professional role among nurses who participated in a summer nurse externship program at an acute care pediatric hospital. Specifically, this article reports the retention and recruitment benefits of a summer nurse externship program for the institution from 1998 through 2003. A total of 153 externs out of the 193 (79.0%) assumed a registered nurse position at the institution, and 77% remained in that role for 12 months. Overall, the nurse extern program for this institution appeared to be an effective recruitment and retention strategy that is on par with the institution and national data for retention and turnover data.     

Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.     

Using complexity theory to build interventions that improve health care delivery in primary care

Previous observational research confirms abundant variation in primary care practice. While variation is sometimes viewed as problematic, its presence may also be highly informative in uncovering ways to enhance health care delivery when it represents unique adaptations to the values and needs of people within the practice and interactions with the local community and health care system. We describe a theoretical perspective for use in developing interventions to improve care that acknowledges the uniqueness of primary care practices and encourages flexibility in the form of intervention implementation, while maintaining fidelity to its essential functions.     

Fatigue and breastfeeding: an inevitable partnership?

Postpartum fatigue is a normal condition that most women experience. Breastfeeding is often associated in women's minds as contributing to the feeling of overall perceived fatigue, and many women indicate that they have ceased breastfeeding because of fatigue. However, the relationship between feeding choice and perceived fatigue has never been established. Two hundred and fifty-three women participated in a study examining whether perceived fatigue differed for bottle-feeding and breastfeeding women at 3 different times during the postpartum period (2-4 days, 6 weeks, and 12 weeks postpartum). Results showed no significant differences for these 2 groups, suggesting that perceived fatigue during the postpartum period is not dependent on feeding choice. Additional analyses examining other variables with a potential effect were nonsignificant. Because perceived physical fatigue does not appear to be dependent on feeding choice, women should be prepared for the feeling of perceived fatigue during the postpartum period while at the same time be reassured that feeding choice is not correlated.     

Cytokine-activated natural killer cells exert direct killing of hepatoma cells harboring hepatitis C virus replicons.

Hepatitis C virus (HCV)-specific impairments in host immunity have been described at multiple levels of the innate and adaptive response, which may lead to viral persistence in the majority of infections. Understanding of HCV-associated immune defects could lead to novel therapeutic advances. Natural killer (NK) cells, the major effector cells of the innate immune system, are functionally impaired in chronic HCV infection. It has been suggested that this phenotype is a result of virus-specific defects in antigen-presenting cells (APCs) that regulate NK cell activity, as normal NK function is restored when they are stimulated ex vivo. In this study, we used human NK cell cytotoxicity assays to evaluate the activation-induced effects of NK cells on the HCV replicon-containing hepatic cells. We found that cytokine-activated NK cells were capable of inducing an HCV-associated, perforin/granzyme-dependent lysis of human hepatoma cells and that this required direct cellular contact and was independent of MHC class I expression levels. In contrast, on removal of cytokine stimulation, NK cells failed to exert any direct cytolytic effect on replicon targets. These findings suggest an important underlying mechanism by which NK cells control HCV infection and, with appropriate understanding of HCV-associated immune defects, could lead to novel therapeutic advances.