Current medical research and opinion
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Retraction Of Publication Retracted Publication
Modulation of sensitization processes in the management of pain and the importance of descending pathways: a role for tapentadol?
Objective: This paper presents and discusses recent evidence on the pathophysiological mechanisms of pain. The role of tapentadol - an analgesic molecule characterized by an innovative mechanism of action (i.e. µ-opioid receptor [MOR] agonism and inhibition of noradrenaline [NA] reuptake [NRI]) - in the modulation of pain, and the most recent pharmacological evidence on this molecule (e.g. the µ-load concept) are also presented and commented upon. Methods: Narrative review. ⋯ The synergistic interaction of these two mechanisms allows a strong analgesic effect by acting on both ascending and descending pathways. Of note, the reduced µ-load of tapentadol has two important consequences: first, it limits the risk of opioid-related adverse events, as well as the risk of dependence; second, the NA component becomes predominant at least in some types of pain with consequent specific clinical efficacy in the treatment of neuropathic and chronic pain. Conclusions: According to these characteristics, tapentadol appears suitable in the treatment of chronic pain conditions characterized by both a nociceptive and a neuropathic component, such as osteoarthritis or back pain.
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Background: Current healthcare professional consensus-generating methodologies work by forcing consensus, which risks corrupting original opinions and often fails to assess prior expert knowledge awareness. Experience gained with a novel method in a progressive life-long rare disease, X-linked hypophosphataemia, which addresses these risks is presented here. Methods: Four case-studies are reported, presenting a novel methodology comprised of two survey rounds. ⋯ Less frequent Round 1 items had various degrees of prompted agreement consensus; some did not reach the consensus threshold of >50% participant agreement. Conclusions: Observed proportional group awareness and consensus is quicker than the Delphi technique and its variants, providing objective assessments of expert knowledge and standardized categorization of items regarding awareness, consensus and prompting. Further, it offers tailored management of each item in terms of educational need and further investigation.
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Objective: To evaluate the risk of death from Alzheimer's disease among cancer survivors in a population-based setting. Methods: Within Surveillance, Epidemiology and End Results (SEER)-9 registries, cancer patients who were diagnosed between 1975 and 2016 have been reviewed. Observed/expected ratios for the risk of death from Alzheimer's disease were calculated for the overall group as well as for clinically defined subgroups. "Observed" is the number of observed deaths from Alzheimer's disease in the studied group, while "Expected" is the number of deaths from Alzheimer's disease in a demographically similar group within the US and within the same period. ⋯ Death from Alzheimer's disease seems to be particularly associated with older age at time of cancer diagnosis (O/E for patients ≥70 years: 1.29 [95% CI: 1.26-1.31] versus O/E for patients <70 years: 1.01 [95% CI: 0.98-1.03]), American Indian race (O/E for American Indian patients: 1.94 [95% CI: 1.30-2.78] versus O/E for White patients: 1.12 [95% CI: 1.10-1.14]), localized tumor stage (O/E for patients with localized disease stage: 1.13 [95% CI: 1.11-1.15] versus O/E for patients with distant disease stage: 1.04 [95% CI: 0.93-1.15]) and brain tumors (O/E for brain tumors: 2.54 [95% CI: 1.42-4.19]). Conclusion: Long-term cancer survivors (≥10 years) are more likely to die from Alzheimer's disease compared to the US general population. This risk seems to be higher among patients with older age at the time of cancer diagnosis, American Indian race and those with brain tumors.
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Randomized Controlled Trial Multicenter Study
IncobotulinumtoxinA for upper- and lower-limb spasticity in Japanese patients.
Introduction: The safety and tolerability of incobotulinumtoxinA 400 U for upper- and lower-limb post-stroke spasticity was assessed in a small cohort of Japanese patients during the open-label lead-in tolerability periods (LITP) of two phase 3 studies (CTI-153029 and CTI-153030; Japan Pharmaceutical Information Centre). Methods: Adult patients received a single incobotulinumtoxinA injection session (total dose of 400 U) in the upper (J-PURE) or lower limb (J-PLUS). Adverse events (AEs) were assessed at 1, 4, 8 and 12 weeks post-injection during the 12 week follow-up. ⋯ Non-serious, transient AEs of special interest reported by two patients in J-PURE comprised muscular weakness and eyelid ptosis. No patient discontinued due to AEs. Conclusion: Preliminary results in this small population suggest that incobotulinumtoxinA 400 U is well tolerated for treating upper- or lower-limb post-stroke spasticity in Japanese patients.
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Meta Analysis
The impact of clinical heterogeneity on conducting network meta-analyses in transthyretin amyloidosis with polyneuropathy.
Objective: The comparative safety and efficacy of tafamidis, patisiran and inotersen treatments for transthyretin amyloidosis with polyneuropathy (ATTR-PN) has not been evaluated in clinical trials. In the absence of head-to-head evidence, indirect treatment comparisons such as network meta-analyses (NMAs) can be performed to evaluate relative effects of treatments. This study aims to assess the feasibility of conducting an NMA of available therapies for ATTR-PN patients. ⋯ Neuropathy outcomes were not evaluated consistently between trials. Conclusions: An NMA of ATTR-PN treatments was not feasible, given the observed cross-trial heterogeneity. This decision highlights the importance of careful consideration for clinical heterogeneity that may threaten the validity of indirect comparisons.