ABSTRACT
The present audit was carried out with the objective of evaluating warning letters (WLs) issued to trial sponsors, clinical investigators and institutional review boards (IRBs) by the United States Food and Drug Administration during a six-year period and compare it with two similar earlier audits. WLs were reviewed and classified as per stakeholders and further categorised as per predefined violation themes. The chi-square test was performed for trend analysis of WLs. A total of 62 WLs were issued to the three stakeholders. The maximum number of WLs were issued to the clinical investigators (36/62, 58.06%), followed by sponsors (19/62, 30.64%), and least to the IRBs (7/62, 11.29%). Among sponsors, lack of standard operating procedures for the monitoring, receipt, evaluation and reporting of post-marketing adverse drug events was the most common violation theme (8/19, 42.1%). Among clinical investigators, deviation from investigational plan was the most common violation theme (31/36, 86.11%.). For IRBs, inadequate documentation was the most common violation theme (6/7, 85.71%). We saw an overall reduction in the number of WLs issued to the stakeholders. Thus, we identified multiple areas on which each stakeholder should work for improvement.
ABSTRACT
The recently published Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial evaluated the hypothesis that rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary prevention. In India, stable cardiovascular disease occurs in a much younger age group relative to the rest of the world. Our critical analysis of COMPASS trial showed that the younger age group appeared to derive greater benefit from the rivaroxaban + aspirin combination (relative to aspirin alone) as seen with number needed to treat metrics as compared to the older age group.
ABSTRACT
BACKGROUND: Plasmablastic lymphoma (PBL), a rare non‑Hodgkin’s lymphoma (NHL) variant specifically associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), expresses well‑differentiated plasma cell markers like CD138, bright CD38, and MUM1; but not conventional B‑cell markers. It occurs at unusual sites like oral cavity and orbit, and has poor survival rates. AIMS: This study serves as a review of a clinical experience with six HIV patients with PBL and observes the spectrum of clinical presentations, histopathologies, and 1‑year outcomes in PBL patients. MATERIALS AND METHODS: This review of six PBL patients was conducted at a tertiary care hospital in eastern India using relevant radiological, histopathogical, and immunohistological studies. RESULTS: Incidence of PBL among HIV patients was 0.58% (6/1,028). Mean CD4 count at presentation was 125.5 ± 71.1 cells/μL. Sites of involvement included pleura, lung parenchyma, suprarenal gland, pelvic cavity, and retroorbital space (one each). Immunohistopathology of biopsied sample in each patient revealed PBL (positive plasma cell markers MUM‑1/ IRF4, CD38, and CD138/syndecan; and negative of B‑cell markers CD3, CD20, and CD30). Three (60%) were positive for Epstein Barr virus (EBV) immunoglobulin G (IgG). Five surviving patients received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen and attained partial remission (PR) after six cycles. Subsequently, three patients were started on EPOCH (etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy; two attained near total regression after 6 months (four cycles). Overall, four patients remained alive with good quality of life at the end of 1 year of follow‑up. CONCLUSION: PBL in HIV occurs at unusual sites with varying aggressivity. This study is too small to comment on the long‑term outcomes of PBL in HIV; however, coadministration of antiretroviral therapy (ART) with standard chemotherapy may improve survival.