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.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.     

Comparison of Methodologies for Calculating Quality Measures Based on Administrative Data versus Clinical Data from an Electronic Health Record System: Implications for Performance Measures

New reimbursement policies and pay-for-performance programs to reward providers for producing better outcomes are proliferating. Although electronic health record (EHR) systems could provide essential clinical data upon which to base quality measures, most metrics in use were derived from administrative claims data. We compared commonly used quality measures calculated from administrative data to those derived from clinical data in an EHR based on a random sample of 125 charts of Medicare patients with diabetes. Using standard definitions based on administrative data (which require two visits with an encounter diagnosis of diabetes during the measurement period), only 75% of diabetics determined by manually reviewing the EHR (the gold standard) were identified. In contrast, 97% of diabetics were identified using coded information in the EHR.The discrepancies in identified patients resulted in statistically significant differences in the quality measures for frequency of HbA1c testing, control of blood pressure, frequency of testing for urine protein, and frequency of eye exams for diabetic patients. New development of standardized quality measures should shift from claims-based measures to clinically based measures that can be derived from coded information in an EHR. Using data from EHRs will also leverage their clinical content without adding burden to the care process.     

Relative pharmacokinetics of three amikacin brands in onco-hemotologic pediatric patients experiencing febrile neutropeina.

Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing. At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands. Whereas at 2 hr following I/V infusion, brands II and I were statistically different. Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I. The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01). The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands. Based upon findings of the present study, all these brands may be used interchangeably in oncology patients. Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance.     

Impact of Varying Stages of Endometriosis on the Outcome of In Vitro Fertilization–Embryo Transfer

Purpose: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. Methods: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. Results: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0,004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. Conclusions: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.     

Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.     

Serum IL-2 and platelet-associated immunoglobulins are good prognostic markers in immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.     

Circadian Rhythms of Heart Rate Variability in Hypertrophic Cardiomyopathy

Background: It has been hypothesized that an interaction between sympathetic nervous activity and an abnormal myocardium plays a role in the development and progression of hypertrophic cardiomyopathy (HCM). Methods: In the present study we investigated cardiac autonomic function by 24-hour spectral analysis of heart rate variability (HRV) in 18 patients with HCM, without evidence of heart failure, and 18 controls of similar age. Results: We found a significant reduction of 24 hour variance in HCM patients relative to controls (15,000 ± 9480 ms² vs 24,720 ± 12,450 ms² respectively; p < 0.05). Moreover, a loss of the expected day-night changes in the low frequency (LF) spectral component (expressed in normalized units), and LF/HF ratio (HF; high frequency component) were observed in HCM patients. Decreased day-night changes in LF/HF ratio were previously reported in patients with mild hypertension, uncomplicated coronary disease, and after myocardial infarction, conditions in which it seems to exist a higher than normal sympathetic activity. No significant correlations were found between HRV indices and echocardiographic standard measures of systolic and diastolic function parameters. Conclusions: These data are consistent with the presence of an alteration in neural modulation of heart period in HCM patients, noninvasively detectable by continuous 24 hour HRV analysis.