Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial

PubMed ID: 15639293Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. Methods 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 µg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 µg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 µg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. Findings 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0·91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0·01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0·01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). Interpretation Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.Schering-Plough Foundation for Liver Research Schering-Plough Commonwealth Scientific and Industrial Research Organisation Erasmus Medisch Centrum, Erasmus MC GlaxoSmithKline, GSK Research and DevelopmentThe study was organised and sponsored by the Foundation for Liver Research, Rotterdam, the Netherlands. Financial support, study medication, and drugs were provided by Schering-Plough International and GlaxoSmithKline Research and Development. Companies providing financial support to the Foundation for Liver Research approved the study design. No funding source had any role in the collection, management, analysis, or interpretation of the data; writing of the report; or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. -- The current standard initial therapy for patients with chronic HBV infection is interferon alfa, lamivudine, or adefovir dipivoxil. 23,24 The introduction of pegylated interferons, with their better pharmacokinetic profiles, has led to higher response rates in chronic hepatitis C, 25,26 and a preliminary study suggested improvements in the response rates in HBeAg-positive patients with chronic hepatitis B. 17 In this large, randomised study, the rate of sustained response (HBeAg loss) in HBeAg-positive patients with chronic hepatitis B assigned pegylated interferon alfa-2b monotherapy was 36% (49 of 136 patients ) . Treatment with pegylated interferon alfa-2b and lamivudine combination therapy was superior to monotherapy at the end of treatment, but not at the end of follow-up. Two previous randomised controlled trials comparing combination therapy and standard interferon monotherapy in chronically HBV-infected patients positive for HBeAg had a shorter duration of lamivudine therapy in the group assigned combination therapy than in the group assigned monotherapy. 5,19 This feature and the timing of the primary efficacy endpoint (after treatment for combination therapy or interferon alone versus on-treatment for lamivudine alone) precluded a definitive conclusion on the efficacy of combination therapy. The investigators concluded that the potential benefit of combining lamivudine with interferon therapy should be investigated further with different regimens of combination therapy. Our study advanced these investigations and helped progress towards a definitive conclusion on the efficacy of combination therapy versus monotherapy in two ways. First, it compared equivalent durations of treatment in the two groups. Second, the long follow-up period extended further beyond the end of treatment with lamivudine than in previous studies, which enabled the extent of relapse to be monitored after 26 weeks of follow-up. Our study highlights differences in response to interferon and to nucleoside analogues. Although patients initially responded to lamivudine, the responses (HBeAg loss and HBV DNA reduction) were not sustained. This finding accords with those of previous studies, with HBeAg relapse rates of 49% to 54%. 12,27 Lack of durability could be due to the mechanism of action of lamivudine, which suppresses viral replication without inducing the HBV-specific immune response necessary for sustained viral eradication. Long-term therapy with lamivudine is not an option because it leads to drug resistance in most cases. 23,28 The lack of this option is particularly difficult for patients with chronic hepatitis B, because many patients develop the disorder when quite young and have to be treated for several decades with resistance-prone medication for which long-term toxicity is unknown. A study with the nucleotide analogue adefovir dipivoxil suggested that response was achieved with development of phenotypic resistance in less than 1·6% of the patients. 10 Future studies are needed to find out whether this response is sustained beyond the end of therapy and whether, with continued therapy, clinically relevant drug resistance remains absent. Our study reveals prospectively the importance of HBV genotype as an independent predictor of response to pegylated interferon treatment for chronic hepatitis B. It accords with earlier retrospective studies, which indicated that HBV genotypes C and D are more difficult to treat than genotypes A and B. 29,30 Future intervention studies for chronic hepatitis B might need stratification according to genotype. The side-effects and frequency of adverse events observed with pegylated interferon alfa-2b monotherapy were similar to those encountered with standard interferon therapy. The rates of dose reductions and discontinuations were similar to those reported with pegylated interferons in patients with chronic hepatitis C, 16,25,26 and with pegylated interferon alfa-2a in chronic hepatitis B. 17 Pegylated interferon alfa-2b is effective and well tolerated for chronic hepatitis B. Rates of sustained clearance of serum HBeAg and reduction of viral load are as high as or higher than those that have previously been reported for any other therapy in this indication. Combination therapy with pegylated interferon alfa-2b and lamivudine is not superior to monotherapy with pegylated interferon alfa-2b. Contributors H L A Janssen and S W Schalm designed the study, prepared the protocol, coordinated the study, collected and analysed the data, and wrote the report. M van Zonneveld participated in data collection and study coordination. H G M Niesters was responsible for virological testing. P Zondervan did histological scoring. B Hansen contributed to and supervised the statistical analysis. H Senturk, S Zeuzem, U S Akarca, Y Cakaloglu, C Simon, T M K So, G Gerken, and R A de Man were involved with data acquisition and critically revised the report. Other members of the HBV 99-01 Study Group Netherlands —B C M Vroom (University Medical Center, Utrecht); C M J van Nieuwkerk (VU University Medical Center, Amsterdam); R A de Vries (Rijnstate Hospital, Arnhem); J Jansen, J Drenth, S J van den Hazel (University Medical Centre Radboud, Nijmegen); J W den Ouden-Muller (St Franciscus Hospital, Rotterdam); A C Tan (Canisius Wilhelmina Hospital, Nijmegen). Belgium —D M Adler (Hopital Erasme, Brussels); P Michielsen (University Hospital, Antwerp); H van Vlierberghe (University Hospital, Gent); F Nevens (University Hospital, Leuven); J Delwaide (Centre Hospitalier Universitaire, Liège); J Henrion (Hopital de Jolimont, Haine St Paul). Germany —S Bein, U Treichel (University Hospital, Essen); J Trojan (J W Goethe Universität, Frankfurt); M P Manns, J Hadem (Medizinische Hochschule, Hannover); C Niederau (St Jozef Hospital, Oberhausen). Denmark —M R Buhl, I M Hansen (Skejby Hospital, Arhus); K Krogsgaard (Copenhagen University Hospital, Hvidovre). Poland —J Cianciara, J Jablonska, J Kozlowska (Medical Academy of Warsaw, Warsaw); D Prokopowicz, R Flisiak (Medical Academy of Bialystok, Bialystok); T Mach (Collegium Medicum UJ, Kraków). Spain —M Buti, A Valdes, R Esteban (Hospital Valle Hebron, Barcelona); M Rodriguez, M Garcia Espiga (Hospital Central de Asturias, Oviedo). Italy —A Andriulli, G Stornaiulo, G B Gaeta (Ospedale Gesùe Maria, Napoli); G Montalto, F D'Antona (Università di Palermo, Palermo). Greece —G E Kitis, P Xiarchos Panagiotis (George Papanikolaou General Regional Hospital, Thessaloniki); N C Tassopoulos (West Attica Hospital, Athens). Turkey —G Ersöz (Ege University Faculty of Medicine, Izmir); S Karayalcin, C Yurdayin, H Bozkaya (Medical School Cebeci Kampusu, Ankara); H Simsek, Y Balaban (Hacettepe University Faculty of Medicine, Ankara), F Tabak (Istanbul University Cerrahpasa Medical School, Istanbul). Israel —Y Lurie (Sauraski Medical Center, Tel-Aviv). Canada —J Heathcote (Toronto Western Hospital, Toronto); S V Feinman (Mount Sinai Hospital, Toronto); S Greenbloom (General Hospital, Etobicoke). Indonesia —D A Sulaiman (Ciptomangunkusomo Hospital, Jakarta). Singapore —R Guan (Mount Elizabeth Medical Center Singapore). Malaysia —I Merican (Institute for Medical Research, Kuala Lumpur). Conflict of interest statement HLAJ is a Clinical Research Fellow from the Netherlands Organisation of Scientific Research. HLAJ, SZ, and SWS have served as consultants or received grants from Schering-Plough, GlaxoSmithKline, and other major pharmaceutical companies. The other authors declare that they have no conflict of interest. Acknowledgments The sponsor of this study was the Rotterdam Foundation for Liver Research. Financial support was given by: Schering-Plough International, Kenilworth, NJ, USA, and GlaxoSmithKline, Research and Development, Greenford, UK. Monitoring was coordinated by Mieke Denys, Denys Research Consultants bvba, De Haan, Belgium. Advice on statistical analysis was given by Wim Hop. Data collection and data management at the trial coordinating centre was supported by Elke Verheij, Hajo Flink, Annick van Nunen, Eva Leeuwenburg, and Maarten Meiburg, Clinical Research Bureau, Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Netherlands. -- -- -- -- -

Management of chronic Hepatitis B infection in the remote primary health care setting: the search for a suitable guideline

Objective: To identify a regionally appropriate guideline for the primary health care management of chronic Hepatitis B patients in the Torres Strait.\ud \ud Design: Literature review. PubMed (1950–November 2009), Nursing and allied health (CINAHL)-CD (1982–November 2009), and the following databases accessed through INFORMIT: Australian Public Affairs Information Service – Health (1978–November 2009), Aboriginal and Torres Strait Health Bibliography (1900–November 2009), Health & Society Database (1980–November 2009), Health Collection (1980–November 2009), Meditext (1968–November 2009), and Rural and Remote Health Database (1966–January 2006) were searched over a 3-month period from September to November 2009. An Internet search of relevant guidelines and recommendations from professional bodies such as the World Health Organization was also performed.\ud \ud Setting: Remote primary health care.\ud \ud Outcome measures: Initial searching identified 144 articles to include based on the provision of recommendations or guidelines for management of Hepatitis B at the primary care level. Included articles were then reviewed for their appropriateness to the remote primary health care setting against a set of five criteria determined at a consensus meeting of eight local medical officers.\ud \ud Results: Eleven articles were included for final review of which none met all five criteria of appropriateness for the remote primary health care setting.\ud \ud Conclusions: Guidelines need to recognize the difficulties of rural and remote practice and present practical alternatives to urban centred recommendations