Salvage chemotherapy for adults with relapsed or refractory lymphoma in Malawi

Abstract Background Lymphoma is highly associated with HIV in sub-Saharan Africa (SSA), which contributes to worse outcomes relative to resource-rich settings, and frequent failure of first-line chemotherapy. However, there are no second-line treatment descriptions for adults with relapsed or refractory lymphoma (RRL) in SSA. Methods We describe HIV+ and HIV- patients with RRL receiving salvage chemotherapy in Malawi. Patients were prospectively treated at a national teaching hospital in Lilongwe, with the modified EPIC regimen (etoposide, prednisolone, ifosfamide, cisplatin) between June 2013 and May 2016, after failing prior first-line chemotherapy. Results Among 21 patients (18 relapsed, 3 refractory), median age was 40 years (range 16–78), 12 (57%) were male. Thirteen patients (62%) were HIV+, of whom 12 (92%) were on antiretroviral therapy (ART) at initiation of salvage chemotherapy, with median CD4 cell count 139 cells/μL (range 12–529) and 11 (85%) with suppressed HIV RNA. Median number of EPIC cycles was 3 (range 1–6), and the commonest toxicity was grade 3/4 neutropenia in 19 patients (90%). Fifteen patients responded (3 complete, 12 partial, overall response rate 71%), but durations were brief. Median overall survival was 4.5 months [95% confidence interval (CI) 2.4–5.6]. However, three patients, all HIV+, experienced sustained remissions. Tolerability, response, and survival did not differ by HIV status. Conclusions The appropriateness and cost-effectiveness of this approach in severely resource-limited environments is uncertain, and multifaceted efforts to improve first-line lymphoma treatment should be emphasized, to reduce frequency with which patients require salvage chemotherapy. Trial registration NCT02835911 . Registered 19 January 2016

Extranodal natural killer/T-cell lymphoma in Malawi: a report of three cases

Abstract Background Extranodal NK/T-cell lymphoma (ENKTCL) reports from sub-Saharan Africa (SSA) are remarkably rare, despite early childhood acquisition and high prevalence of the causative infectious agent, Epstein-Barr virus (EBV), and frequent occurrence of other lymphoproliferative disorders causally associated with EBV. Case presentations At a national teaching hospital in Malawi, three patients of African descent were seen with ENKTCL between 2013 and 2014. Patients were aged between 29 and 60 years, two with craniofacial involvement and one with a primary abdominal tumor, and all were HIV-negative. All had systemic B symptoms, and two severely impaired performance status. On histologic review, morphology and immunophenotyping demonstrated classical ENKTCL features in all cases, including diffuse proliferations of intermediate-to-large atypical lymphocytes with high mitotic activity and extensive background necrosis, positivity for CD3 and CD56, and negativity for CD20. By in situ hybridization, all three tumors were positive for EBV-encoded RNA (EBER). Baseline plasma EBV DNA was also markedly elevated for all three patients. Due to radiotherapy and chemotherapy limitations, patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with rapid disease progression. All three patients died from progressive lymphoma within 3 months of initial diagnosis. Conclusions Our experience with these three patients in Malawi can highlight that ENKTCL does indeed occur in SSA, increase familiarity with ENKTCL among clinicians and pathologists throughout the region, and emphasize the need for better diagnosis and treatment for this neglected population

Antineoplastic Drug Contamination on the Outside of Prepared Infusion Bags

Eight Dutch hospital pharmacies took wipe samples of prepared infusion bags containing 5 fluorouracil just before distribution to the wards. The samples were tested with high-performance liquid chromatography and triple quadrupole mass spectroscopy. The limit of detection was 10 ng per swipe. None of the 146 samples had a detectable amount of 5-fluorouracil. The outside of infusion bags containing antineoplastic drugs prepared in these eight Dutch hospital pharmacies were not contaminated and, therefore, were not a risk factor with regard to exposure of hospital workers to antineoplastic drugs

Neurobiological Correlates in Forensic Assessment : A Systematic Review

Background: With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour and biological risk factors could improve forensic assessments. Objective: To provide an overview of the current evidence about biological risk factors that predispose people to antisocial and violent behaviour, and determine its usefulness in forensic assessment. Methods: A systematic literature search was conducted using articles from PsycINFO, Embase and Pubmed published between 2000 and 2013. Results: This review shows that much research on the relationship between genetic predisposition and neurobiological alterations with aggression is performed on psychiatric patients or normal populations. However, the number of studies comparing offenders is limited. There is still a great need to understand how genetic and neurobiological alterations and/or deficits are related to violent behaviour, specifically criminality. Most studies focus on only one of the genetic or neurobiological fields related to antisocial and/or violent behaviour. To reliably correlate the findings of these fields, a standardization of methodology is urgently needed. Conclusion: Findings from the current review suggest that violent aggression, like all forms of human behaviour, both develops under specific genetic and environmental conditions, and requires interplay between these conditions. Violence should be considered as the end product of a chain of life events, during which risks accumulate and potentially reinforce each other, displaying or triggering a specific situation. This systematic review did not find evidence of predispositions or neurobiological alterations that solely explain antisocial or violent behaviour. With better designed studies, more correlation between diverse fields, and more standardisation, it might be possible to elucidate underlying mechanisms. Thus, we advocate maintaining the current case-by-case differentiated approach to evidence-based forensic assessment

Systematic review of the mechanisms and evidence behind the hypocholesterolaemic effects of HPMC, pectin and chitosan in animal trials

Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action

Species-dependent binding of new synthesized bicalutamide analogues to albumin by optical biosensor analysis

The binding of some novel bicalutamide analogues to human serum albumin (HSA) and rat serum albumin (RSA) was investigated by surface plasmon resonance (SPR) based optical biosensor technique. The serum protein binding of the bicalutamide analogues was determined and compared to that of the parent compound. Furthermore, HSA and RSA were used as target plasma proteins, in order to highlight possible differences among species when performing pharmacokinetic studies. HSA and RSA were covalently immobilized on carboxymethyl dextran matrixes, using an amine coupling procedure. The anchoring method was validated by determining the dissociation constant (K-D) of a standard analyte to confirm that the binding properties of the proteins were maintained. The ranking of the bicalutamide analogues for their HSA and RSA bound fractions was used to compare the behaviour of the two albumins. Most of the bicalutamide analogues showed higher binding levels with respect to the lead compound, (R)-bicalutamide. Further, meaningful differences in the binding level to the two serum proteins were obtained. The dissociation constants (K-D) of the interaction between the lead compound, (R)-bicalutamide, and the two proteins were calculated. As a result, the K-D obtained with HSA was one order of magnitude higher than that obtained with RSA. The observed differences in the HSA and RSA bonding of the bicalutamide analogues increase the knowledge on the possible low reliability in extrapolating the distribution data obtained on animals to humans. This work demonstrates that SPR based optical biosensor technique is well suited for the medium-high throughput screening of compounds' ligand binding to serum albumins

Addressing the challenge of high-priced prescription drugs in the era of precision medicine: A systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks

markdownabstractCONTEXT: Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. METHOD: A systematic review of Pubmed, the Financial Times, the New York Times, the Wall Street Journal and the Guardian was performed to identify articles related to the pricing of medicines. FINDINGS: Changes in drug life cycles have dramatically affected patent medicine markets, which have long been considered a self-evident and self-sustainable source of income for highly profitable drug companies. Market failure in combination with high merger and

Gene doping:an overview and current implications for athletes

<p>The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping, and is prohibited for competitive athletes. As yet there is no conclusive evidence that that gene doping has been practiced in sport. However, given that gene therapy techniques improve continuously, the likelihood of abuse will increase.</p><p>A literature search was conducted to identify the most relevant proteins based on their current gene doping potential using articles from Pubmed, Scopus and Embase published between 2006 and 2011. The final list of selected proteins were erythropoietin, insulin-like growth factor, growth hormone, myostatin, vascular endothelial growth factor, fibroblast growth factor, endorphin and enkephalin, a actinin 3, peroxisome proliferator-activated receptor-delta (PPAR delta) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C). We discuss these proteins with respect to their potential benefits, existing gene therapy experience in humans, potential risks, and chances of detection in current and future anti-doping controls.</p><p>We have identified PPARd and PEPCK-C as having high potential for abuse. But we expect that for efficiency reasons, there will be a preference for inserting gene target combinations rather than single gene doping products. This will also further complicate detection.</p>

PRISMA flow chart.

<p>Schematic overview of the study selection process. FT: Financial Times, NYT: New York Times, WSJ: Wall Street Journal</p