Prescription Trends in Complex Regional Pain Syndrome: A Retrospective Case-Control Study.

OBJECTIVE: The objective of this study was to evaluate discrepancies in prescription trends for analgesic medications in complex regional pain syndrome (CRPS) patients based on recommendations in the literature. DESIGN: We conducted a retrospective case-control study. SUBJECTS: A total of 2510 CRPS patients and 2510 demographic-matched controls participated in this study. METHODS: The SlicerDicer feature in Epic was used to find patients diagnosed with CRPS I or II between January 2010 and November 2022. An equal number of age-, gender-, and race-matched controls without a CRPS diagnosis were retracted from Epic. General and CRPS-associated prescription frequencies for the following classes were retrieved for both cases and controls: benzodiazepines, bisphosphonates, calcitonin, capsaicin, neuropathic pain medications, NSAIDs, opioids, and steroids. RESULTS: A total of 740 (29%) CRPS patients and 425 (17%) controls were prescribed benzodiazepines (95% CI 0.1-0.15), 154 (6.1%) CRPS patients and 52 (2.1%) controls were prescribed capsaicin (95% CI 0.03-0.05), 1837 (73%) CRPS patients and 927 (37%) controls were prescribed neuropathic pain medications (95% CI 0.05-0.34), 1769 (70%) CRPS patients and 1217 (48%) controls were prescribed opioids (95% CI 0.19-0.25), 1095 (44%) CRPS patients and 1217 (48%) controls were prescribed steroids (95% CI 0.08-0.14), and 1638 (65%) CRPS patients and 1765 (70%) controls were prescribed NSAIDs (95% CI -0.08-0.02), p < 0.001 for all classes. With CRPS-associated prescriptions, (95% CI 0.05-0.16, p < 0.001) more CRPS patients were prescribed opioids (N = 398, 59%) than controls (N = 327, 49%). CONCLUSIONS: CRPS is difficult to treat with significant variance in suggested treatment modalities. Based on the results of our study, there is a divergence between some published recommendations and actual practice.

Flower isoforms promote competitive growth in cancer.

In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require an adaptive immune system1,2. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing3, prevent developmental malformations3,4 and replace old tissues during regeneration5. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins3,4,6. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated6. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed4,6,7. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease8-17. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage18. This would be undesirable for humans because it might make tumours more aggressive19-21. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.

An animal homolog of plant Mep/Amt transporters promotes ammonia excretion by the anal papillae of the disease vector mosquito Aedes aegypti.

The transcripts of three putative ammonia (NH3/NH4 (+)) transporters, Rhesus-like glycoproteins AeRh50-1, AeRh50-2 and Amt/Mep-like AeAmt1 were detected in the anal papillae of larval Aedes aegypti Quantitative PCR studies revealed 12-fold higher transcript levels of AeAmt1 in anal papillae relative to AeRh50-1, and levels of AeRh50-2 were even lower. Immunoblotting revealed AeAmt1 in anal papillae as a pre-protein with putative monomeric and trimeric forms. AeAmt1 was immunolocalized to the basal side of the anal papillae epithelium where it co-localized with Na(+)/K(+)-ATPase. Ammonium concentration gradients were measured adjacent to anal papillae using the scanning ion-selective electrode technique (SIET) and used to calculate ammonia efflux by the anal papillae. dsRNA-mediated reductions in AeAmt1 decreased ammonia efflux at larval anal papillae and significantly increased ammonia levels in hemolymph, indicating a principal role for AeAmt1 in ammonia excretion. Pharmacological characterization of ammonia transport mechanisms in the anal papillae suggests that, in addition to AeAmt1, the ionomotive pumps V-type H(+)-ATPase and Na(+)/K(+)-ATPase as well as NHE3 are involved in ammonia excretion at the anal papillae.