Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery

OBJECTIVE: Acute renal failure can be treated with continuous renal replacement therapy (CRRT) or intermittent hemodialysis. There is no difference in mortality, although patients treated with CRRT may have a higher rate of renal recovery. Given these considerations, an estimate of the costs by modality may help in choosing the method of dialysis. As such, the objective of this study was to estimate the cost of CRRT and intermittent hemodialysis in the intensive care unit and to explore the impact of renal recovery on subsequent clinical outcomes and costs among survivors. DESIGN: Retrospective cohort study of all patients who developed acute renal failure and required dialysis between April 1, 1996, and March 31, 1999. SETTING: Two tertiary care intensive care units in Calgary, Canada. PATIENTS: A total of 261 critically ill patients. INTERVENTIONS: None. MEASUREMENTS: All patients were followed to determine in-hospital and subsequent clinical outcomes (survival and frequency of renal recovery). The immediate and potential long-term costs of CRRT and intermittent hemodialysis were measured. MAIN RESULTS: The cost of performing CRRT ranged from Can 3,486 dollars to Can 5,117 dollars per week, depending on the modality and the anticoagulant used, and it was significantly more expensive than intermittent hemodialysis (Can 1,342 dollars per week). Survivors with renal recovery spent significantly fewer days in hospital (11.3 vs. 22.5 days, p<.001) and incurred less healthcare costs (11,192 dollars vs. 73,273 dollars, p<.001) over the year after hospital discharge compared with survivors who remained on dialysis. CONCLUSIONS: Immediate cost savings could be achieved by increasing the use of intermittent hemodialysis rather than CRRT for patients with acute renal failure in the intensive care unit. Because of the high cost of ongoing dialysis, CRRT may still be an economically efficient treatment if it improves renal recovery among survivors; further study in this area is required.     

Sydenham's chorea: a clinical follow-up of 65 patients

Sydenham's chorea, the neurological manifestation of rheumatic fever, is the most common acquired chorea of childhood. In this retrospective study, the authors aim to present the clinical and laboratory findings of 65 Sydenham's chorea patients, followed up in a clinic over less than 7 years. The mean age at the onset of the symptoms was 11.7 +/- 2.6 years (range, 6-17 years). Of the patients, 63% were female and 37% were male (male/female: 1.7/1). Chorea was generalized in 78.5% of the patients, right hemichorea in 12.3%, and left hemichorea 9.2%. There was a history of rheumatic fever in 30.8% of the patients. Echocardiographic study showed cardiac valve involvement in 70.5% of 61 patients. Brain magnetic resonance imaging, which was performed on only 18 patients, was evaluated as normal in all. Electroencephalography was also performed on only 18 patients and showed abnormal waves in 50% of them. Pimozide was mostly the first choice of drug therapy. Nevertheless, drug therapy was not needed in 18.5% of the patients. The recovery period of the first attack of the chorea was 1 to 6 months in 51.7% of the patients. The recurrence rate was 37.9%. In conclusion, Sydenham's chorea is still an important health problem in Turkey with respect to its morbidity.     

Effect of Pap smear screening on cervical cancer stage at diagnosis: results from the Korean National Cancer Screening Program

ObjectiveWe aimed to determine the differences in stage at diagnosis of cervical cancer among Korean women according to screening history.MethodsUsing linkage data from the Korean Central Cancer Registry and Korean National Cancer Screening Program (KNCSP), we included 18,388 women older than 30 years who were newly diagnosed with cervical cancer between 2013 and 2014 and examined their screening history. Between individuals, age group and socioeconomic status were matched to control for potential confounders.ResultsSignificantly more cases of carcinoma in situ (CIS) were diagnosed in the ever-screened (71.77%) group than in the never-screened group (54.78%), while localized, regional, distant, and unknown stage were more frequent in the never-screened group. Women in the ever-screened group were most likely to be diagnosed with CIS than with invasive cervical cancer (adjusted odds ratio [aOR]=2.40; 95% confidence interval [CI]=2.18–2.65). The aOR for being diagnosed with CIS was highest among women who were screened 3 times or more (aOR=5.10; 95% CI=4.03–6.45). The ORs were highest for women screened within 24 months of diagnosis and tended to decrease with an increasing time since last screening (p-trend <0.01).ConclusionThe KNCSP for cervical cancer was found to be positively associated with diagnosis of cervical cancers at earlier stages among women aged 30 years or older. The benefit of screening according to time was highest for women screened within 24 months of diagnosis.     

Rosiglitazone Attenuates Liver Inflammation in a Rat Model of Nonalcoholic Steatohepatitis

Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone’s effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.     

Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo

Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This observation is particularly intriguing in the context of cardiac hypertrophy, where serum response factor transactivation is a key event necessary for the induction of cardiac hypertrophy in response to increased afterload. We have previously reported that MuRF1, which is also a titin-associated protein, exerts antihypertrophic activity in vitro. In the present study, we induced cardiac hypertrophy in mice lacking MuRF1 and MuRF2 to distinguish the physiologic role of these divergent proteins in vivo. We identified for the first time that MuRF1, but not MuRF2, plays a key role in regulating the induction of cardiac hypertrophy, likely by its direct interactions with serum response factor. These studies describe for the first time distinct and nonoverlapping functional characteristics of MuRF1 and MuRF2 in response to cardiac stress in vivo.     

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response

The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. CONCLUSION: These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.     

Characterization of a model to independently study regression of ventricular hypertrophy

BACKGROUND: Although a host of studies catalogue changes that occur with the development of left ventricular hypertrophy (LVH), there is little information about features related solely to LVH regression. This is due, in part, to a lack of animal models to study this question. While traditional models of aortic banding have provided useful information regarding the development of LVH, a similarly effective model is necessary to study mechanisms associated with LVH regression. MATERIALS AND METHODS: Minimally invasive transverse arch banding was performed in C57BL6 mice using a slipknot technique. Twenty-eight days later, the band was removed. Carotid Doppler velocity gradients were serially measured to assess the degree of aortic constriction. Echocardiography, histology, electron microscopy, and real-time polymerase chain reaction were used to assess functional, structural, and genetic aspects of hypertrophy. RESULTS: Banding of the transverse arch created the expected increase in aortic velocity and gradient between the left and right carotid artery, which normalized with relief of the constriction. Pressure overload resulted in a robust hypertrophic response as assessed by heart weight/body weight ratios, gross and microscopic histology, transthoracic echocardiography, electron microscopy, and hypertrophy gene expression. These markers were reversed within 1 week following debanding and were maintained for up to 4 weeks. Mortality rate for the cumulative procedure was 5% over a 2-month period. CONCLUSIONS: These results demonstrate a safe, effective, and reproducible method of promoting LVH regression-avoiding the need for endotracheal intubation, mechanical ventilation, and a second invasive surgery to remove the constriction. The simplicity of this technique combined with the well-known advantages of using the mouse species makes this model both unique and relevant. Ultimately, this model will facilitate focused study of independent mechanisms involved with LVH regression.     

Creating a transatlantic research enterprise for preventing Alzheimer's disease

In recognition of the global problem posed by Alzheimer's disease and other dementias, an international think-tank meeting was convened by Biocat, the Pasqual Maragall Foundation, and the Lou Ruvo Brain Institute in February 2009. The meeting initiated the planning of a European Union-North American collaborative research enterprise to expedite the delay and ultimate prevention of dementing disorders. The key aim is to build parallel and complementary research infrastructure that will support international standardization and inter-operability among researchers in both continents. The meeting identified major challenges, opportunities for research resources and support, integration with ongoing efforts, and identification of key domains to influence the design and administration of the enterprise.     

Normative data and factorial structure of the Turkish version of the Temperament and Character Inventory

Cloninger's dimensional psychobiological model of personality accounts for both normal and abnormal variation in 2 major personality components: temperament and character. Here, we examined the psychometric properties of the Turkish version of the Temperament and Character Inventory (TCI) in a healthy Turkish population, obtaining normative data for the Turkish TCI. The study was conducted in healthy volunteers at both Karadeniz Technical University School of Medicine and Atatürk University School of Medicine (n = 683). The Turkish sample had significantly lower mean scores on Novelty Seeking and Reward Dependence and higher mean scores on Harm Avoidance than the American sample. The Turkish sample had significantly lower scores on Self-Directedness, Cooperativeness, and Self-Transcendence. Self-Directedness and Harm Avoidance, Cooperativeness and Reward Dependence, and Cooperativeness and Self-Directedness were intercorrelated. The Cronbach coeficients were between 0.60 and 0.85 on temperament dimensions, and between 0.82 and 0.83 on character dimensions. The lowest Cronbach coefficients were found in Reward Dependence (0.60) and Persistence (0.62). A principal axis factor analysis with a 4-factor solution revealed the highest loadings on Novelty Seeking and Harm Avoidance and relatively weaker loadings on Reward Dependence and Persistence. A 3-factor solution for character subscales indicated the highest loadings on Cooperativeness and Self-Transcendence. The factorial structure was consistent with Cloninger's 7-factor model of personality, and test-retest indicated a good stability of scores over time. The reliability and factorial validity of the Turkish version of the TCI are therefore supported.