Current medical research and opinion
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Purpose: Over the last two decades, increasing attention has been paid to environmental toxins and their effects on the female reproductive system. Endocrine disrupting chemicals (EDCs) are exogenous substances or mixtures that can mimic the action of steroid hormones and interfere with their metabolism. Advanced glycation end products (AGEs) are proinflammatory molecules that can interact with cell surface receptors and mediate the triggering of proinflammatory pathways and oxidative stress. ⋯ They favor PCOS/OC development through different mechanisms that finally lead to hormonal and metabolic disruption and epigenetic modifications. Conclusions: Environmental toxin exposure in PCOS women could favor neoplastic transformation by exacerbating and potentiating some PCOS features. Further research, although difficult, is needed in order to prevent further diffusion of these substances in the environment, or at least to provide adequate information to the population considered at risk.
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Multicenter Study
The mirogabalin ALDAY phase 3 program in pain associated with fibromyalgia: the lessons learned.
Aims: The main aim of this work was to identify and to share the lessons learned from the negative outcome of the mirogabalin ALDAY phase 3 clinical program in pain associated with fibromyalgia. These lessons are important to improve planning and design of future phase 3 programs in fibromyalgia. Methods: A systematic review from Cochrane Library, Medline, Embase, clinicaltrials.gov, pharmaceutical companies, and regulatory agencies' websites, was carried out starting from the development of gabapentin, the first α2δ ligand studied for the treatment of neuropathic pain and ending with the mirogabalin program. ⋯ Outcome: In terms of main lessons learned from ALDAY, the first was the need for a comprehensive patient-focused strategy to preliminarily identify the challenges of fibromyalgia based on patient perspective and study complexity. Second, there was a need for a harmonized, truly patient-centric, global regulatory guidance accepted by regulatory agencies. Third, ALDAY proved that a phase 2 proof of concept, dose ranging study is necessary before commencing any phase 3 program in fibromyalgia.
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Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.
Aim: The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults. Methods: We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE and The Cochrane Register of Studies; date of the final search was November 2018. ⋯ Conclusion: This systematic review of 11,000+ participants demonstrates that topical diclofenac is effective for acute pain, such as sprains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain. Formulation does play a part in effectiveness but needs further studies.
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Objective: Oral supplementation with iron is a standard intervention for treating or preventing iron deficiency with or without anemia. Over the last few decades, various forms of oral iron have been developed to improve treatment tolerability and iron bioavailability. In this review, we gathered research data regarding the use of iron protein succinylate since it was first marketed in the 1980s. ⋯ The change in all parameters was similar or higher with iron protein succinylate compared to other iron treatments evaluated. Overall, study groups receiving iron protein succinylate reported the lowest rate of adverse events. Conclusions: Although all iron treatments analyzed are effective and safe, our results suggest that iron protein succinylate may be an excellent choice to treat iron deficiency and anemia due to its superior effectiveness and tolerability.
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Background: Renal cell carcinoma (RCC) is the most common type of renal malignancy with 87% frequency. As a global health problem, kidney cancer is responsible for 2.2% of new cancer cases. One of the highly effective mechanisms that renal cancer cells avoid in the immune system is PD-1 and PD-L1 interaction. ⋯ Following tyrosine kinase inhibitors, checkpoint inhibitors have a great influence on treatment of advanced RCC, especially the combination of these two strategies. In 2019 these combined strategies demonstrated 5% complete remission with up to 60% objective response rate. While not immediately, but perhaps in the near future, advanced RCC will become a manageable chronic disease, even if a cure is not possible.