We appreciate Dr Prommer's letter and would like to make several comments in reply.The type of opioid-induced hyperalgesia (OIH) described in our case report does not involve most of the cellular and subcellular mechanisms described in detail by Dr Prommer. Outlined mechanisms apply to OIH associated with opioid maintenance doses and/or opioid withdrawal (OIH MW ). However, the case presented by us concerned OIH associated with the use of very high and escalating opioid doses (OIH HD ). This type of OIH is not mediated through the opioid receptor system. From a mechanistic and management point of view it is important to differentiate OIH MW from OIH HD . 1 Dr Prommer suggests that ketamine is "clearly the best current initial management," for OIH HD because opioid "dose reduction or detoxification is not practical". We do not share Dr Prommer's view. Available evidence clearly suggests that opioid dose reduction or opioid rotation are effective strategies for abolishing or attenuating OIH HD . 1 Ketamine may be useful as an adjuvant therapeutic agent because some of the symptoms associated with OIH HD seem to be mediated through the N-methyl-D-aspartate (NMDA) receptor system. 2 Dr Prommer is quite firm about the mechanisms underlying OIH MW . However, there is still some uncertainty about the major mechanisms that mediate OIH MW and several receptor systems went unmentioned. For example, dynorphin is upregulated by chronic morphine exposure, which results in the activation of non-NMDA voltage-gated calcium channels. 3,4 Similarly, cholecystokinin is upregulated at the level of the rostral ventromedial medulla and periaqueductal gray, which results in the activation of pain facilitating pathways that descend to spinal cord. [5][6][7][8][9] In addition, neurokinin-1 antagonists, cyclooxygenase inhibitors, and nitric oxide synthase inhibitors have all been shown to attenuate OIH MW . 10 In summary, we would like to reiterate our opinion that opioid dose reduction or opioid rotation should be the first-line treatment for OIH HD .
Background: Women with high mammographic density have an increased breast cancer risk and also a lower mammographic tumor detectability. Nevertheless, these women are currently screened with mammography only. MRI could lead to earlier tumor detection, because of its higher sensitivity. To study the additional value of MRI, a parallel-group randomized controlled trial design is needed with one group receiving mammography and the other group receiving mammography and MRI. With this design it is possible to determine the proportion of interval tumors within each arm. A reduction in interval tumors is a precondition of effectiveness, because this represents clinically relevant cancer detection, rather than overdiagnosis. Study design: DENSE is a multicenter randomized trial, carried out in the Dutch biennial screening program (age range 50-75 years). Mammographic density is measured using a fully-automated volumetric method (Volpara™). Participants with extremely dense breasts (ACR4) and a negative mammogram are randomized to ‘additional MRI’ (n=7,237) versus ‘current practice’ (n=28,948). After randomization, only the intervention arm is asked for consent (single-consent prerandomized design). The intervention consists of a dynamic breast MRI with gadolinium-based contrast medium (Gadovist®) and is carried out for 3 screening rounds. The primary outcome is the difference in proportion of interval tumors between the arms. Secondary outcomes are the number of MRI screen-detected tumors, proportion false-positives, quality of life, breast cancer mortality and costs. Conclusion: DENSE investigates the (cost-)effectiveness of screening with mammography and MRI compared to mammography alone in women with extremely dense breasts aged 50-75 years. Inclusion started in December 2011. Citation Format: Marleen Emaus, Wouter Veldhuis, Marije Bakker, Evelyn Monninkhof, Nico Karssemeijer, Maurice van den Bosch, Petra Peeters, Willem Mali, Carla van Gils. Design of the DENSE trial: MRI as an additional screening modality to detect breast cancer in women aged 50-75 years with extremely dense breasts. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B10.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.