Determination of HCV genotypes and viral loads in chronic HCV infected patients of Hazara Pakistan

Hepatitis C Virus (HCV) genotype and viral load are two significant predictive variables knowledge of which might persuade treatment decisions. The objective of the present study was to identify the distribution of different HCV genotypes circulating in the study area and to estimate viral load in chronically HCV infected patients. Out of total 305 HCV positive patients, 177 (58%) were males and 128 (42%) were females. Frequency breakup of the HCV positive patients was 169, 69, 38 and 29 from Abbottabad, Mansehra, Haripur and Battagram districts respectively. Out of the total 305 tested serum samples, 255 (83.06%) were successfully genotyped whereas 50 (16.4%) samples were found with unclassified genotypes. Among typable genotypes, 1a accounted for 21 (6.8%) 1b for 14 (4.6%), 2a for 4 (1.31%) 3a for 166 (54.42%) and genotype 3b for (8.19%). Twenty five (8.19%) patients were infected with mixed HCV genotypes. Viral load distribution was classified into three categories based on its viral load levels such as low (< 60, 0000 IU/mL), intermediate (60,0000-80,0000 IU/mL) and high (> 80,0000 IU/mL). The baseline HCV RNA Viral load in HCV genotype 3 infected patients was 50 (26.17%), 46 (24.08%) and 95 (49.73%) for low, intermediate and high categories respectively. For genotypes other than 3, these values for low, intermediate and high viral load categories were 50 (43.85), 35 (30.70) and 29 (25.43) respectively. Pre-treatment viral load in patients with untypable genotype was 19 (38.00%), 5 (20.00%) and 11 (44.00%) for low, intermediate and high viral load categories. Viral load distribution was also categorized sex wise; for males it was 58 (32.76%), 26 (14.68%) and 93 (52.54%) whereas for females it was 40 (31.25%), 34 (26.56%) and 54 (42.18%) for low, intermediate and high viral load respectively. In conclusion HCV genotype 3a is the most prevalent genotype circulating in Hazara Division like other parts of pakistan. Pre-treatment viral load is significantly high (p 0.014) in patients infected with HCV genotype 3 as compared to other genotypes

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naive APC with Eastern Cooperative Oncology Group performance status <= 2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m(2) and nab-paclitaxel 125 mg/m(2) every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66-93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade > 3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy