Effectiveness and cost-effectiveness of initial combination therapy with interferon/peginterferon plus ribavirin in patients with chronic hepatitis C in Germany: a health technology assessment commissioned by the German Federal Ministry of Health and Social Security

OBJECTIVES: The purpose of this health technology assessment (HTA), commissioned by the German Federal Ministry of Health and Social Security, was to systematically review the evidence for the effectiveness and cost-effectiveness of antiviral treatment (AVT) with interferon (INF) or peginterferon (PegIFN) in combination with ribavirin (RBV) in treatment-na?ve patients with chronic hepatitis C (CHC) and to apply these data in the context of the German health-care system. METHODS: We performed a systematic literature search on effectiveness and cost-effectiveness of AVT and summarized results using meta-analysis and evidence tables. We applied the German Hepatitis C Model (GEHMO), a decision-analytic Markov model, to determine long-term clinical effectiveness, costs, and incremental cost-effectiveness ratios (ICER) of the examined treatment strategies. Model parameters were derived from German databases, published international randomized clinical trials (RCT), and a Cochrane Review. RESULTS: Overall, nine RCTs, two HTA reports, one Cochrane review, two meta-analyses, and seven economic evaluations met the inclusion criteria. These studies indicate that PegIFN + RBV achieved the highest sustained virological response rates (SVR) (54-61 percent), followed by IFN + RBV (38-54 percent) and IFN monotherapy (11-21 percent). Based on our meta-analysis, PegIFN + RBV reduced cases without SVR by 17 percent compared with INF + RBV. International cost-effectiveness studies indicate that INF+ RBV is cost-effective when compared with INF monotherapy. For PegIFN + RBV, our decision analysis yielded an ICER of 9,800 Euros per quality-adjusted life-year gained. CONCLUSIONS: This HTA suggests that initial combination therapy prolongs life, improves quality of life, and is cost-effective in patients with CHC. Peginterferon plus ribavirin is the most effective and efficient treatment among the examined options. However, because not all chronic hepatitis C patients will develop progressive liver disease, a thorough assessment of the eligibility and appropriateness of treatment with combination therapy must be performed in each individual patient.     

Precursor frequencies of T-cells reactive to insulin in recent onset type 1 diabetes mellitus

T-cell mediated autoimmune beta-cell destruction is an important component of type 1 diabetes (T1D) and insulin is a critical antigen recognized by autoreactive T-cells. The aim of this study was to investigate the precursor frequency of insulin reactive T-cells in type 1 diabetes. We studied 19 T1D patients, 12 age-matching non-diabetic healthy siblings and 12 non-diabetic healthy parents. Limiting dilution analysis (LDA) was performed to insulin and tetanus toxoid (TT). A progressive decrease in the number of negative cultures at increasing cell concentrations that is represented by a low goodness-of-fit (GoF, low Chi-square), was seen with the TT response in all three groups; precursor frequencies and GoF were similar in patients, siblings, and parents. Reactivity to insulin, however, showed low precursor frequencies in patients and siblings and the LDA to insulin demonstrated dramatic decreases in the number of positive cultures at higher cell concentrations leading to a high GoF in patients and siblings compared to parents. This saw-toothed pattern of reactivity to insulin is indicative of multiple hit kinetics and implies that the response is regulated. Consequently the precursor frequency of insulin autoreactive cells in patients and their siblings is probably much higher than calculated.     

The Dutch Heart Health community intervention 'Hartslag Limburg': results of an effect study at individual level

'Hartslag Limburg' (Dutch for Heartbeat Limburg), a regional cardiovascular diseases (CVD) prevention program, integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors. The present paper focuses on the effects of the community intervention on fat intake and physical activity. The project was based on community organization principles and health education theories and methods. In order to implement the intervention, nine local Health Committees were set up, each organizing activities that facilitate and encourage people to adopt a healthier lifestyle. A pre-test-post-test control group design with two post-tests was used to evaluate the intervention. At baseline, representative random cohort research samples were selected in the Maastricht region and in a control region. Data on fat intake and physical activity, and on the psychosocial determinants of these behaviors, were gathered by means of mail surveys. The present study indicates that the intervention had a significant effect on fat reduction, especially among respondents aged 相似文献   

Monitoring and evaluation of side effects of chemotherapy in patients with colon cancer

This study aimed to monitor and evaluate the occurrence and intensity level of nausea, vomiting and diarrhea in patients with colon cancer, submitted to outpatient chemotherapy, who received nursing information for handling these symptoms. Study participants were 17 patients, who were treated with 5-Fluorouracil and low doses of folinic acid, at the Adult Outpatient Chemotherapy Clinic of the Hospital S?o Paulo/Federal University of S?o Paulo, Brazil. Instruments were elaborated for registering these symptoms' occurrence and intensity level and a patient guide for handling them. The information and patient monitoring were carried out by the nurse during the consultations. The results showed that most of the patients (82.4%) displayed at least one of the signs and symptoms under study between the first and the 21st day of the treatment cycle. Nausea was the most frequent symptom (76.5%), with a peak on the 4th and 5th day of the cycle, followed by diarrhea (70.5%), with a peak on the 7th day, and vomiting (53.0%), with a peak on the 5th day. Regarding the intensity of these symptoms, most patients were classified as level 1, which was established as acceptable for this study. These results indicate that the nursing instructions and the continuous monitoring contributed to the effectiveness of the patient's symptom management.     

Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to other biological state markers and self reported-ethanol intake

AIMS: In a variety of clinical and forensic situations long term use of alcohol must be monitored. In this project we explore the utility of fatty acid ethyl esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to distinguish teetotallers/moderate/social drinkers from alcoholics or individuals drinking at harmful levels. PATIENTS AND METHODS: FAEE levels from 18 alcohol-dependent patients in detoxification were contrasted with those of 10 social drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid phase microextraction and gas chromatography mass spectrometry. C(FAEE), as sum of the concentrations of four esters, was compared to a major FAEE, ethyl palmitate. PEth was measured in heparinized whole blood with a high pressure liquid chromatography (HPLC) method. Drinking validation criteria include self reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT). RESULTS: Receiver-operating characteristic (ROC) curve analysis for C(FAEE), indicated a sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By using a cut-off of 0.4 ng/mg, C(FAEE) identified 94.4% correctly. C(FAEE) and ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were C(FAEE) and PEth (r = 0.527; P = 0.025). No significant correlation was found between C(FAEE) and total grams of ethanol consumed last month, blood-alcohol concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100% accuracy. CONCLUSIONS: The data suggest that C(FAEE) is a potentially valuable marker of chronic intake of high quantities of ethanol. Furthermore, the results indicate that a reasonable and provisional FAEE cut-off to distinguish between social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/mg.     

Removal of silicone breast implants and review of literature

Silicone breast implants have a finite life span and may need changing over the lifetime of the patient. The experience with removing first- and second-generation implants is frustrating, because thick capsules often form, in association with rupture and spread of the silicone gel into the surrounding tissue. Different techniques have been employed to try and avoid an unnecessarily large incision, yet still control the dissection so that entire capsule and contained silicone can be removed en bloc. The authors describe a technique that facilitates atraumatic removal using an effective and time-saving vacuum principle.     

Prenatal sonographic findings in trisomy 22: five case reports and review of the literature.

OBJECTIVE: The purpose of this study was to survey prenatal sonographic findings and their frequencies in fetuses with complete trisomy 22 and to identify potential sonographic markers of this aneuploidy. METHODS: Sonographic examinations of 5 fetuses were performed and chromosome analysis was conducted after amniocentesis, chorionic villus sampling, cordocentesis, or a combination thereof. The sonographic findings were compared with other prenatal cases in the literature. RESULTS: Intrauterine growth restriction, hypoplastic femurs, nuchal thickening, cerebellar defects, and oligohydramnios were the most frequently observed anomalies in all considered cases of late first-, second-, and third-trimester scans. CONCLUSIONS: These anomalies represent commonly accepted sonographic markers for chromosomal defects in general, some recognizable from the time of first-trimester screening (12th-14th weeks of gestation) and stress their importance for prenatal sonographic scans.