Screening for acquired cystic kidney disease: A decision analytic perspective

Screening for acquired cystic kidney disease: A decision analytic perspective. Acquired cystic kidney disease (ACKD) increases the risk of renal malignancy, and many authors suggest routine screening of dialysis patients for ACKD and renal tumors. However, they have defined neither the target population, the optimal screening strategy, the magnitude of its benefit, nor its risk. We used decision analysis to evaluate strategies of performing either computed tomography (CT) or ultrasound every three years on all dialysis patients and annually on patients found to have cysts. We compared these strategies to a strategy of seeking cysts and cancer only if these are clinically suspected. The baseline analysis shows that both CT and ultrasound may decrease cancer deaths by half for patients with a life expectancy of 25 years. Screening for ACKD offers these patients as much as a 1.6 year gain in life expectancy. However, for the majority of patients beginning renal replacement therapy, age or comorbid disease substantially limits life expectancy. For such patients, the gain in life expectancy from an ACKD screening program is measured in days. Sensitivity analyses show that the benefit of screening depends on the rate of malignant transformation, which needs better definition. The gain in life expectancy does not appear to be large enough to justify an ACKD screening program for the entire ESRD population. However, for the youngest and healthiest patients, a screening program would be of benefit. The magnitude of this benefit is uncertain, because the analysis was consistently biased in favor of the screening strategies

Age and quality of in-hospital care of patients with heart failure

Background: Elderly patients may be at risk of suboptimal care. Thus, the relationship between age and quality of care for patients hospitalized for heart failure was examined. Methods: A cross-sectional study based on retrospective chart review was performed among a random sample of patients hospitalized between 1996 and 1998 in the general internal medicine wards, with a principal diagnosis of congestive heart failure, and discharged alive. Explicit criteria of quality of care, grouped into three scores, were used: admission work-up (admission score); evaluation and treatment during the stay (evaluation and treatment score); and readiness for discharge (discharge score). The associations between age and quality of care scores were analysed using linear regression models. Results: Charts of 371 patients were reviewed. Mean age was 75.7 (±11.1) years and 52% were men. There was no relationship between age and admission or readiness for discharge scores. The evaluation and treatment score decreased with age: compared with patients less than 70 years old, the score was lower by −2.6% (95% CI: −7.1 to 1.9) for patients aged 70 to 79, by −8.7% (95% CI: −13.0 to −4.3) for patients aged 80 to 89, and by −19.0% (95% CI: −26.6 to −11.5) for patients aged 90 and over. After adjustment for possible confounders, this relationship was not significantly modified. Conclusions: In patients hospitalized for congestive heart failure, older age was not associated with lower quality of care scores except for evaluation and treatment. Whether this is detrimental to elderly patients remains to be evaluate

Predictors of inappropriate hospital days in a department of internal medicine

Background This study aimed to identify predictors of inappropriate hospital days in a deparUnent of internal medicine, as a basis for quality improvement interventions. Methods The appropriateness of 5665 hospital days contributed by 500 patients admitted to the Department of Internal Medicine, Geneva University Hospitals, Switzerland, was assessed by means of the Appropriateness Evaluation Protocol. Predictor variables included patient's age and sex, manner of admission and discharge, and characteristics of hospital days (weekend, holiday, sequence). Results Overall, 15% of hospital admissions and 28% of hospital days were rated as inappropriate. In multivariate models, inappropriate hospital days were more frequent among patients whose admission was inappropriate (odds ratio [OR] = 5.3, 95% CI: 3.1-8.4) and among older patients (80-95 years: OR = 3.6. 95% CI: 1.7-7.0, versus <50 years). The likelihood of inappropriateness also increased with each subsequent hospital day, culminating on the day of discharge, regardless of the total length of stay. Conclusions This study identified both the admission and the discharge processes as important sources of inappropriate hospital use in a department of internal medicine. The oldest patients were also at high risk of remaining in the hospital inappropriately. Surprisingly, long hospital stays did not generate a higher proportion of inappropriate days than short hospital stays. This information proved useful in developing interventions to improve the hospitalization proces

Prohormones in the early diagnosis of cardiac syncope

Background--The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregionalproadrenomedullin. Methods and Results--We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P < 0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of < 77 pmol/L and an ED probability of < 20% had a sensitivity and a negative predictive value of 99%. Conclusions--The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope

The treatment response of chronically hepatitis C virus-infected patients depends on interferon concentration but not on interferon gene expression in peripheral blood mononuclear cells.

International audienceThe current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain, the measurement of interferon-inducible genes seems not be the best strategy to predict treatment outcome

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy