Background December 2019 marked the inception of a global pandemic, with cases being reported worldwide. In the developing nations with scarce healthcare resources, the reliance on healthcare workers who are amply prepared to withstand the prevailing scenario is indispensable. Our study aimed to assess the level of preparedness of doctors working in various hospitals across Pakistan to combat coronavirus disease 2019 (COVID-19). Methods We conducted an online questionnaire-based survey in May 2020 to estimate the level of preparedness of doctors working in various departments of various private and public hospitals across Pakistan. The survey comprised 36 questions, with items evaluating the provision of adequate protective equipment, training, mental health resources, and sound collaboration between healthcare workers and the hospital management during the COVID-19 crisis. Results A total of 346 doctors responded to the survey, among whom 56.4% were working in public sector hospitals and 46.5% were working more than five days per week. Of those included, 87.6% were being provided with disposable gloves, but 72.8% and 43.4% of respondents professed to having no access to eye protective equipment and gowns, respectively. Only 35.3% of respondents claimed to be trained regarding the use of personal protective equipment and 28.95% were being tested. Of the physicians, 43.4% claimed to have no proper triage system for the suspected patients and 98.3% were concerned about transmitting the disease to their family members. Of the doctors, 53.5% reported that there was sound collaboration between the hospital management and healthcare staff. Conclusion The survey provided evidence of inadequate delivery of personal protective equipment and training to doctors working in various hospitals across Pakistan. A sound collaboration between the hospital management and departments needs to be addressed.
Background: Clonal plasma cells in multiple myeloma (MM) over express b-cell lymphoma-2 protein (BCL2). Which is the target for venetoclax (VEN). VEN has a promising efficacy and a favorable safety profile in MM patients. This review highlights the efficacy of VEN for the treatment of relapsed refractory (RR) MM. Methodology: We performed a comprehensive database search on four major databases(PubMed, Embase, Cochrane, and Clinical trials.gov). Our search strategy included MeSH terms and keywords for multiple myeloma and VEN, including trade names and generic names, from the date of inception of the database to April 2020.The initial search revealed 782 articles. After excluding review articles, duplicates, and non-relevant articles,we included six studies(four clinical trials and two retrospective studies), which reported an overall response rate (ORR) in RRMM patients. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of VEN. We pooled the results of the experimental arms of included trials using the inverse variance method and logit transformation. Between studies,the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 568 patients from four clinical trials [Moreau et al.2019, the BELLINI trial, (n=291, venetoclax arm= 194, placebo arm= 97)], Costa et al. 2018 (n=42), Kumar et al. 2017(n=66), and Moreau et al. 2017 (n=66)] and two retrospective studies (Kambhampati et al. 2020 (n= 47) and Sidiqi et al.2019 (n=56)). Among which 563 patients were evaluable for the treatment outcomes. One hundred and forty two patients (25%) had t(11:14)mutation. The median age of the patients ranged from 64-66 years, and the median number of prior therapies was ≥2. The median dose of venetoclax ranged from 50 mg/day to 1200 mg/day in dose-escalation cohorts of clinical trials while in the retrospective study by Kambhampati, S et al., the median dose of venetoclax was 800 mg/day. The pooled overall response rate (ORR) for all patients who received venetoclax (n=466) was 57% (95% confidence interval (CI) 0.34-0.77, p<0.01; I2=95%), with the highest rates of 84% and 79% being reported from phase III trial using VEN + bortezomib (V) + dexamethasone (d) by Moreau et al.(2019), and VEN + carfilzomib + d in phase II clinical trial by Costa et al. (2018), respectively (Figure 1A). A minimum ORR of 21% was observed in a retrospective study by Siddiqi et al. (2019). Among 142 patients with positive t(11:14) in all studies, ORR was 56% (95% CI 0.44-0.68, p<0.11; I2=44%) (Figure 1B) with the highest rate of 100% being reported from Costa et al., though the number of patients was small. Among 362 patients with no t(11:14) ,ORR was 33% (95% CI 0.16-0.55, p<0.01: I2=89%), with the highest rate of 56% being reported from Moreau et al. in a phase III trial using VEN-Vd (Figure 1C). The highest median duration of response (DOR) (23.4 months) was reported with combination therapy of VEN-Vd. Two hundred and thirty eight (42%) of the patients discontinued VEN, among whom 132 (55%) were reported to have progressive disease. The most common grade≥3 hematological adverse effects were neutropenia, thrombocytopenia, and anemia. The gastrointestinal distress was the most common non-hematological toxicity reported in all the studies. Sixty four (33%) patients died on VEN arm vs. 24 (25%) on placebo in the BELLINI trial, the trend of OS is non-significantly better in VEN arm in t(11:14) while OS is non-significantly worse in non t(11:14) group. Conclusion: VEN is an effective treatment option for relapsed and refractory multiple myeloma patients with t(11:14) translocation. The overall response rate and the duration of response are better in patients with t(11:14). The CANOVA trial is ongoing now to better answer the debatable question of VEN efficacy in t(11;14) MM patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau.
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