Occurrence,detection and ecotoxicity studies of selected pharmaceuticals in aqueous ecosystems- a systematic appraisal

Pharmaceutical compounds (PCs) have globally emerged as a significant group of environmental contaminants due to the constant detection of their residues in the environment. The main scope of this review is to fill the void of information on the knowledge on the African occurrence of selected PCs in environmental matrices in comparison with those outside Africa and their respective toxic actions on both aquatic and non-aquatic biota through ecotoxicity bioassays. To achieve this objective, the study focused on commonly used and detected pharmaceutical drugs (residues). Based on the conducted literature survey, Africa has the highest levels of ciprofloxacin, sulfamethoxazole, lamivudine, acetaminophen, and diclofenac while Europe has the lowest of all these PC residues in her physical environments. For ecotoxicity bioassays, the few data available are mostly on individual groups of pharmaceuticals whereas there is sparsely available data on their combined forms.     

Management of blood pressure disorders in individuals with spinal cord injury

Blood pressure regulation is impacted by a spinal cord injury (SCI) due to impaired descending sympathetic vascular control. Common blood pressure problems in the SCI population include persistently low blood pressure with bouts of orthostatic hypotension and autonomic dysreflexia, which are more prevalent in individuals with lesions above the sixth thoracic vertebral level; however, they may occur regardless of the neurological level of injury. Although blood pressure disorders adversely impact daily function and quality of life, most individuals with SCI do not acknowledge this association. Few pharmacological options have been rigorously tested for safety and efficacy to manage blood pressure disorders in the SCI population. Furthermore, clinical management of any one blood pressure disorder may adversely impact others, as such treatment is complicated and not often prioritized.     

Metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) by Streptomyces griseolus CYP105A1 and its variants

In the field of drug development, technology for producing human metabolites at a low cost is required. In this study, we explored the possibility of using prokaryotic water-soluble cytochrome P450 (CYP) to produce human metabolites. Streptomyces griseolus CYP105A1 metabolizes various non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, meclofenamic acid, and ibuprofen. CYP105A1 showed 4′-hydroxylation activity towards diclofenac, mefenamic acid, flufenamic acid, tolfenamic acid, and meclofenamic acid. It should be noted that this reaction specificity was similar to that of human CYP2C9. In the case of mefenamic acid, another metabolite, 3′-hydroxymethyl mefenamic acid, was detected as a major metabolite. Substitution of Arg at position 73 with Ala in CYP105A1 dramatically reduced the hydroxylation activity toward diclofenac, flufenamic acid, and ibuprofen, indicating that Arg73 is essential for the hydroxylation of these substrates. In contrast, substitution of Arg84 with Ala remarkably increased the hydroxylation activity towards diclofenac, mefenamic acid, and flufenamic acid. Recombinant Rhodococcus erythrocyte cells expressing the CYP105A1 variant R84A/M239A showed complete conversion of diclofenac into 4′-hydroxydiclofenac. These results suggest the usefulness of recombinant R. erythropolis cells expressing actinomycete CYP, such as CYP105A1, for the production of human drug metabolites.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Patient and clinician experiences with cross-border reproductive care: A systematic review

ObjectivesThis review analyzes the experiences of patients and clinicians with regards to international cross-border reproductive care (CBRC) for the purpose of conception.MethodsElectronic databases PubMed, Embase, Web of Science, and Scopus were searched using ‘medical tourism’ AND ‘assisted reproductive technology’ from 1978 to 2020.ResultsPredominant patient motivators for CBRC were cost and legality of assisted reproduction technology (ART) in one's home country, followed by cultural factors like shared language, religion, and cultural familiarity. Clinicians suggested global laws for CBRC would reduce the potential for exploitation of vulnerable populations but believed the enactment of international regulations unlikely and, even if enacted, difficult to enforce.ConclusionsWhile patient and clinician experiences with CBRC varied, patients frequently cited financial and legal reasons for pursuing CBRC, while many providers had concern for the patient’s safety.Clinical practice implicationsThis review recommends clinicians involved in family planning counsel patients seeking treatment abroad by: (i) informing patients of the risks and benefits of treatment abroad, (ii) establishing guidelines and standards for clinicians on resuming patient care post-CBRC, and (iii) creating a directory of reputable CBRC clinicians and experts.     

Left Atrial Appendage Occlusion,A Misnomer?: Where Do We Go From Here?

The importance of the left atrial appendage (LAA) as the source of thromboembolism including stroke in patients with nonvalvular atrial fibrillation is well documented, with more than 90% of ischemic strokes related to a LAA thrombus. Although oral anticoagulation has been the standard of care, approximately 50% to 60% of patients either have contraindications to oral anticoagulation or do not continue the medication beyond the first year. This led to the development of local site-specific therapy to occlude the LAA by either surgical or transcatheter means. Despite marked advancements, incomplete LAA closure with surgical and transcatheter approaches remains frequent. The etiology of incomplete LAA closure and its clinical implications remain unclear. Multiple strategies are in development including changes in deployment techniques, a new device design, and alternative approaches to leak closure.