Rejected

To evaluate the dose trajectory of new opioid tapers and estimate the percentage of patients with sustained tapers at long-term follow-up.

Consuming addictive drugs is often initially pleasurable, but escalating drug intake eventually recruits physiological anti-reward systems called opponent processes that cause tolerance and withdrawal symptoms. Opponent processes are fundamental for the addiction process, but their physiological basis is not fully characterized. Here, we propose an opponent processes mechanism centered on the endocrine stress response, the hypothalamic-pituitary-adrenal (HPA) axis. We focus on alcohol addiction, where the HPA axis is activated and secretes β-endorphin, causing euphoria and analgesia. Using a mathematical model, we show that slow changes in the functional mass of HPA glands act as an opponent process for β-endorphin secretion. The model explains hormone dynamics in alcohol addiction and experiments on alcohol preference in rodents. The opponent process is based on fold-change detection (FCD) where β-endorphin responses are relative rather than absolute; FCD confers vulnerability to addiction but has adaptive roles for learning. Our model suggests gland mass changes as potential targets for intervention in addiction.

Idiopathic retroperitoneal fibrosis is a rare fibro-inflammatory disease that can be associated with other IgG4-related diseases (IgG4-RDs). It is exceedingly uncommon to encounter this condition in a patient with Riedel's thyroiditis (RT), another disease in the IgG4-RD family. We present the case of a 53-year-old man with a history of RT who presented for severe localized lower abdominal and suprapubic pain due to obstructive uropathy from extensive retroperitoneal fibrosis. The biopsy of the mass demonstrated fibro-inflammatory tissue, and its immunohistochemistry was notable for IgG4-positive plasma cells. This case highlights the challenge associated with the diagnosis and management of this rare manifestation of IgG4-RD. In a patient with a history of any form of IgG4-RDs, providers should be vigilant for any signs or symptoms that suggest the development of fibrosis in other organs.

May-Thurner syndrome is an anatomical condition characterized by compression of the left common iliac vein by the right common iliac artery, causing venous outflow obstruction. It is an uncommon cause of deep vein thrombosis and is more prevalent among women. This paper highlights the importance of considering May-Thurner syndrome in young males without risk factors presenting with left lower limb pain, as endovascular treatment may be required.

There is a lack of national report of the labour neuraxial analgesia (NA) rates in China in recent years, especially after the national promotion policy. The adverse maternal and perinatal outcomes associated with NA in China are also unknown. The aim of this study is to estimate the trends of NA rates from 2012 to 2019, to evaluate the effect of national policy on promoting NA and to identify the association between NA and adverse outcomes in China.

Pain management is important for ensuring early mobilization after hip arthroplasty; however, the optimal components remain controversial. Recently, the quadratus lumborum block has been proposed as an analgesic option. The current study tested the hypothesis that the posterior quadratus lumborum block combined with multimodal analgesia decreases morphine consumption after hip arthroplasty.

Galcanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, was recently approved for migraine prophylaxis. The pharmacokinetic/pharmacodynamic (PK/PD) relationship between galcanezumab concentration and inhibition of capsaicin-induced dermal blood flow (CIDBF) was evaluated using first-in-human data following 6 single subcutaneous doses (1 to 600 mg) or multiple (4) 150-mg doses every 2 weeks in 7 cohorts (7 actively treated subjects and 2 placebo-treated healthy subjects). Galcanezumab pharmacokinetics were best described by a 1-compartment model with delayed first-order absorption/linear elimination. Apparent estimates (between-subject variability) of clearance, volume of distribution, absorption rate constant, and lag time were 0.0106 L/h (27%CV), 11.2 L (21%CV), 0.0192 h (89%CV), and 0.202 hours, respectively. Estimated elimination half-life was about 30 days. An effect compartment link model described the concentration-effect relationship; estimated maximum inhibitory effect was 70.5%, and 50% maximum inhibitory effect concentration (IC ) was 1060 ng/mL. Galcanezumab showed dose- and concentration-dependent potent and durable inhibition of CIDBF. Simulated effect compartment concentrations were maintained above IC after 12 weeks of dosing. Near-maximal CIDBF inhibition occurred with 150 mg biweekly for 12 weeks lasting ≥24 weeks or with ≥30 mg every 2 weeks or 195 mg every 13 weeks. Quantitative modeling of galcanezumab PK/PD supported dose selection for the phase 2 proof-of-concept study.

Intake excessive arsenic (As) is related to the occurrence of peripheral neuropathy. However, both the underlying mechanism and the preventive approach remain largely unknown. In the present study, As treatment significantly decreased the mechanical withdrawal threshold and increased the titer of anti-myelin basic protein antibody in rats, accompanied with damaged BNB. The levels of inflammatory cytokines and proteolytic enzymes were also significantly upregulated. However, administration of MeCbl in As-treated rats significantly reversed the decline in hindfoot mechanical withdrawal threshold, as well as BNB failure and sciatic nerve inflammation. Repeated As treatment in athymic nude mice indicated that sciatic nerve inflammation and mechanical hyperalgesia were T cell-dependent. These data implicated that MBP-activated autoimmunity and the related neuroinflammation probably contributed to As-induced mechanical hyperalgesia and MeCbl exerted a protective role probably via maintenance the integrity of BNB and inhibition of neuroinflammation.

This study explored factors that underpin decisions to seek emergency department (ED) care for chronic non-cancer pain in patients identifying as culturally and linguistically diverse (CALD) or Australian-born.