High doses of interferon in combination with ribavirin are more effective than the standard regimen in patients with HCV genotype 1 chronic hepatitis

BACKGROUND/AIMS: The aim of the present, open-labelled, controlled study was to determine whether 5 MU of interferon (IFN) alpha 2b combined with a standard dose of ribavirin might increase the rate of viral clearance in all patients with chronic HCV hepatitis or at least in those with an unfavourable genotype. METHODS: A total of 298 previously untreated patients with chronic hepatitis C were randomized to 5 or 3 MU of interferon alpha 2b 3 times per week with 1000-1200 mg of ribavirin daily (148 and 150 patients, respectively). Patients were treated for 12 months and observed for 6 months posttreatment. RESULTS: In patients infected with HCV genotype 1, the sustained virologic response was 37.8% (95% CI 27.3-48.1) with IFN 5 MU and 19.2% (95% CI 10.1-28.2) with IFN 3 MU (P=0.008). Out of 45 sustained responders with genotype 1, 31 (69%) had received 5 MU and 14 (31.1%) the standard 3 MU dose of IFN in combination with ribavirin (P=0.01). Of the 86 responders infected with genotype non-1, 39 (45.3%) were from the 5 MU IFN group and 47 (54.6%) were from the 3 MU IFN group; these figures were not significant. At the multivariate analysis of baseline features for all patients, the variables with an independent effect for a sustained response were genotype non-1 (odds ratio (OR) 3.98, 95% CI 2.36-6.40), and the histological grading (score 0-2) (OR 2.48, 95% CI 1.12-5.51) and staging (score 0-1) (OR 1.73, 95% CI 1.02-2.95). For patients with genotype 1 only the high regimen of IFN entered the model (OR 2.39, 95% CI 1.13-5.05), whereas for patients with genotype non-1 an age of <40 years (OR 2.64, 95% CI 1.23-5.70) and staging (score 0-1) (OR 2.38, 95% CI 1.07-5.28) were independent predictors of a sustained response. CONCLUSIONS: Our study suggests that when treating naive patients with genotype 1, there is a significant increase in the rate of sustained virologic clearance by increasing the dose of IFN given in combination with ribavirin.     

Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated with autoimmune related disorders

Objective The prevalence of chronic unexplained anaemia was analysed in patients with autoimmune thyroid disease (ATD). Design The presence of chronic unexplained anaemia, defined as anaemia not related to evident or occult bleeding and/or to erythropoietic disorders, was retrospectively assessed and compared in patients with nonautoimmune thyroid disease (NATD) and in patients with ATD. Subjects and measurements Biochemical and morphological parameters of anaemia were investigated and characterized in 1643 consecutive Caucasian outpatients with thyroid disease. In 991 patients, thyroid disease had a nonautoimmune origin. ATD was diagnosed in 652 patients (71 had Graves’ disease and 581 had Hashimoto's thyroiditis and its variants). In 145 patients ATD was associated with other autoimmune disorders. Results The presence of chronic unexplained anaemia was diagnosed in 123 patients (7·5%). Forty‐eight had a thalassaemic trait, representing 2·9% of the whole sample. A true chronic unexplained anaemia was recorded in 75/1643 (4·6%). The occurrence of unexplained anaemia was similar in patients with NATD (1·9%) and in those with isolated ATD (2·96%; P = NS) but increased in patients with ATD and autoimmune related disorders (ARD) compared to patients with isolated ATD and/or with NATD (28·3%; both P < 0·0001; RR = 9·56 and 14·75, respectively). Chronic unexplained anaemia was virtually absent in hyperthyroid patients and was more prevalent in hypothyroid than in euthyroid patients with ATD (P = 0·0047; RR = 2·104). Conclusions These results indicate that the increased frequency of chronic anaemia in patients with ATD is essentially due to the presence of concomitant autoimmune gastrointestinal diseases.     

Pelvic inflammatory disease in the People's Republic of China: aetiology and management

OBJECTIVES: To study the causes of pelvic inflammatory disease (PID) in Shenyang, Northeastern China, and to assess the efficacy of the syndromic management flowchart for PID recommended by World Health Organization (WHO). METHODS: 200 outpatients with PID attending Gynaecologic Clinic of No. 1 and No. 2 hospital of China Medical University in Shenyang, and 155 control women without symptoms underwent pelvic examination, and were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma hominis (MH), bacterial vaginosis (BV), Candida albicans (CA) and Trichomonas vaginalis (TV). RESULTS: In PID patients, the prevalence of MH was 26%, of BV 26%, of CT 16%, of CA 11%, of TV 4% and of NG 2.5%. In the control population, prevalences were 5.2%, 8.4%, 0%, 5.2%, 0.7%, 0% respectively. MH, BV and CT were significantly more common in PID patients than in controls (P<0.01). One hundred and thirty-seven of the 200 patients with PID (68.5%) returned for follow-up. Symptoms had resolved completely in 64 (47%), and had improved in 68 (50%). There was no improvement in five (4%). CONCLUSIONS: The management protocol for female lower abdominal pain recommended by WHO is effective in this setting.     

Effects of α-human atrial natriuretic peptide in guinea-pig isolated heart

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (α-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by α-hANP on myocardial function. A maximal increase of +LV (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM α-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM α-hANP. Similar effects have also been induced by α-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM α-hANP) was induced by picomolar concentrations of α-hANP, whereas a progressive decrease, which was maximal (−28%; P < 0.01) at 50 nM α-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.     

Chlamydial heat-shock protein-60 antibody and correlation with Chlamydia pneumoniae in atherosclerotic plaques

A study was performed to determine whether serum antibody to Chlamydial heat-shock protein-60 (CHSP-60) and C-reactive protein (CRP) were associated with the presence of Chlamydia pneumoniae in atheromatous plaques in 75 patients. The mean (+/-SD) ELISA optical density (OD) of anti-CHSP-60 was 0.19+/-0.15 in 54 patients with detectable C. pneumoniae antigen, versus an OD of 0.11+/-0.08 in 21 patients without detectable C. pneumoniae I antigen (P=.008). Higher anti-CHSP-60 at an OD > or =0.12 was present in 38 (70.4%) of patients with detectable C. pneumoniae in atheromas, compared with 5 (23.8%) of patients without C. pneumoniae antigen (P<.001; 2-tailed test). The mean CRP concentration was 7.4+/-10.3 mg/L in patients with detectable C. pneumoniae antigen, versus 5.7+/-6.1 mg/L in those without (P=.556). Immune response to CHSP-60 may play a role in atherogenesis, but CRP serum levels does not appear to be related to C. pneumoniae infection.     

Low vitamin B6 and folic acid levels are associated with retinal vein occlusion independently of homocysteine levels

Retinal vein occlusion (RVO) is one of the most common retinal vascular disorders. During the last years, high levels of homocysteine (Hcy) have been demonstrated to be an independent risk factor for RVO. Aim of this study was to investigate the association among circulating B-group vitamins, Hcy and RVO. Thus, we studied 262 RVO patients and 262 age- and sex-comparable healthy subjects. Serum vitamin B6 was measured by HPLC, serum folic acid and vitamin B12 by radioimmunoassay and plasma Hcy by FPIA.

Blood levels of vitamin B6, folate and Hcy, but not of vitamin B12, were found to be significantly different in patients as compared to healthy subjects. At the univariate analysis, the lowest tertile of vitamin B6 [odds ratio (OR) 4.03; 95% confidence interval (CI) 2.58–6.31; P < 0.0001)] and folate (OR 6.13; 95% CI 3.85–9.76, P < 0.0001), and the highest tertile of Hcy (OR 8.08; 95% CI 5.05–12.92, P < 0.0001) were found to be significantly associated with RVO. Moreover, at multivariate analysis, after adjustment for traditional cardiovascular risk factors, Hcy, and circulating levels of vitamins, respectively, the lowest tertile of vitamin B6 (OR 3.29; 95% CI 1.89–5.70, P < 0.0001) and folate (OR 5.41; 95% CI 3.08–9.51, P < 0.0001) and the highest tertile of Hcy (OR 2.58; 95% CI 1.12–5.94, P < 0.0001) maintained their significant association with RVO. In conclusion, the present study documents, on a large sample of patients, that low vitamin B6 levels, low folic acid levels and elevated Hcy levels are each independently associated with RVO.     

Real-world clinical practice of intracoronary radiation therapy as compared to investigational trials.

Intracoronary radiation therapy (IRT) is well established in clinical practice as an effective treatment for in-stent restenosis. We aimed to determine if the 6-month clinical outcome of patients treated postapproval for marketing [commercial radiation (CR)] is equivalent to those patients enrolled in the Washington Radiation for In-Stent Restenosis Trials [Gamma WRIST and Beta WRIST; investigational radiation (IR)]. The 6-month clinical outcome of 110 consecutive patients with 125 lesions who received IRT (gamma, (192)Ir, 15-18 Gy, n = 6; or beta, (32)P, 20 Gy, n = 20; or (90)Sr/Y, 18.4-23.0 Gy, n = 99) in CR was compared with the 6-month clinical outcome of 117 patients with 117 lesions who received IRT ((192)Ir, 15 Gy, n = 65, in Gamma WRIST; and (90)Y, 20.6 Gy, n = 52, in Beta WRIST) in IR. Patients in CR were treated with wider radiation margins. The CR received antiplatelet therapy for at least 6 months and the IR for 1 month. The baseline characteristics of both groups were similar. Use of atheroablation devices was less in CR than IR (15.2% vs. 32.8%, respectively; P = 0.001). The overall major adverse cardiac events (death, Q-wave myocardial infarction, and target vessel revascularization; 18.2% vs. 29.1% in IR; P = 0.05) were significantly lower in the CR when compared with patients in the IR. The real-world clinical practice of IRT demonstrates lower events and better clinical outcomes. This is most likely a result of implementation of the lessons learned from the clinical trials such as optimizing the dosimetry by using a higher dose, treating wider margins to minimize edge effect, and administering prolonged antiplatelet therapy to abolish late thrombosis.     

Budget Impact Analysis of a Biosynthetic Mesh for Incisional Hernia Repair

Purpose

With the development of newer prostheses for hernia repair, it is nowadays difficult to understand the total cost of managing patients treated with these advanced medical devices, especially in the complex abdomen, in which various complications may occur. The aim of this study was to determine the economic implications of these prostheses in order to inform decision making in the management of incisional hernia repair.