Physician Characteristics Associated With Opioid Prescribing After Same-Day Breast Surgery in Ontario, Canada: A Population-Based Cohort Study.

Background and Objectives: Opioid overprescribing in patients undergoing breast surgery is a concern, as evidence suggests that minimal or no opioid is needed to manage pain. We sought to describe characteristics of opioid prescribers and determine associations between prescriber's characteristics and high opioid prescribing within 7 days of same-day breast surgery. Methods: Patients ≥18 years of age who underwent same-day breast surgery in Ontario, Canada from 2012 to 2020 were identified and linked to prescriber data. The primary outcome was current high opioid prescribing defined as >75th percentile of the mean oral morphine equivalents (OME; milligrams). Prescriber characteristics including age, sex, specialty, years in practice, practice setting, and history of high (>75th percentile) opioid prescribing in the previous year were captured. Associations between prescriber characteristics and the primary outcome were estimated in modified Poisson regression models. Results: The final cohort contained 56,434 patients, 3469 unique prescribers, and 58,656 prescriptions. Over half (1971/3469; 57%) of prescribers wrote ≥1 prescription that was >75th percentile of mean OME of 180 mg, of which 50% were family practice physicians. Adjusted mean OMEs prescribed varied by specialty with family practice specialties prescribing the highest mean OME (614 ± 38 mg) compared to surgical specialties (general surgery [165 ± 9 mg], plastic surgery [198 ± 10 mg], surgical oncology [154 ± 14 mg]). Whereas 73% of first and 31% of second prescriptions were provided by general surgery physicians, family practice physicians provided 2% of first and 51% of second prescriptions. Prescriber characteristics associated with a higher likelihood of high current opioid prescribing were family practice (risk ratio [RR], 1.56; 95% confidence interval [CI], 1.35-1.79 compared to general surgery), larger community practice setting (RR, 1.34; 95% CI, 1.05-1.71 compared to urban), and a previous high opioid prescribing behavior (RR, 2.28; 95% CI, 2.06-2.52). Conclusions: While most studies examine surgeon opioid prescribing, our data suggest that other specialties contribute to opioid overprescribing in surgical patients and identify characteristics of physicians likely to overprescribe.

Survival of Patients With Head and Neck Merkel Cell Cancer: Findings From the Pan-Canadian Merkel Cell Cancer Collaborative.

Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Due to its relatively low incidence and limited prospective trials, current recommendations are guided by historical single-institution retrospective studies. Objective: To evaluate the overall survival (OS) of patients in Canada with head and neck MCC (HNMCC) according to American Joint Committee on Cancer 8th edition staging and treatment modalities. Design, Setting, and Participants: A retrospective cohort study of 400 patients with a diagnosis of HNMCC between July 1, 2000, and June 31, 2018, was conducted using the Pan-Canadian Merkel Cell Cancer Collaborative, a multicenter national registry of patients with MCC. Statistical analyses were performed from January to December 2022. Main Outcomes and Measures: The primary outcome was 5-year OS. Multivariable analysis using a Cox proportional hazards regression model was performed to identify factors associated with survival. Results: Between 2000 and 2018, 400 patients (234 men [58.5%]; mean [SD] age at diagnosis, 78.4 [10.5] years) with malignant neoplasms found in the face, scalp, neck, ear, eyelid, or lip received a diagnosis of HNMCC. At diagnosis, 188 patients (47.0%) had stage I disease. The most common treatment overall was surgery followed by radiotherapy (161 [40.3%]), although radiotherapy alone was most common for stage IV disease (15 of 23 [52.2%]). Five-year OS was 49.8% (95% CI, 40.7%-58.2%), 39.8% (95% CI, 26.2%-53.1%), 36.2% (95% CI, 25.2%-47.4%), and 18.5% (95% CI, 3.9%-41.5%) for stage I, II, III, and IV disease, respectively, and was highest among patients treated with surgery and radiotherapy (49.9% [95% CI, 39.9%-59.1%]). On multivariable analysis, patients treated with surgery and radiotherapy had greater OS compared with those treated with surgery alone (hazard ratio [HR], 0.76 [95% CI, 0.46-1.25]); however, this was not statistically significant. In comparison, patients who received no treatment had significantly worse OS (HR, 1.93 [95% CI, 1.26-2.96)]. Conclusions and Relevance: In this cohort study of the largest Canada-wide evaluation of HNMCC survival outcomes, stage and treatment modality were associated with survival. Multimodal treatment was associated with greater OS across all disease stages.

Variation in opioid filling after same-day breast surgery in Ontario, Canada: a population-based cohort study.

BACKGROUND: Postoperative pain management practices in breast surgery are variable, with recent evidence that approaches for minimizing or sparing opioids can be successfully implemented. We describe opioid filling and predictors of higher doses in patients undergoing same-day breast surgery in Ontario, Canada. METHODS: In this retrospective population-based cohort study, we used linked administrative health data to identify patients aged 18 years or older who underwent same-day breast surgery from 2012 to 2020. We categorized procedure types by increasing invasiveness of surgery: partial, with or without axillary intervention (P ± axilla); total, with or without axillary intervention (T ± axilla); radical, with or without axillary intervention (R ± axilla); and bilateral. The primary outcome was filling an opioid prescription within 7 or fewer days after surgery. Secondary outcomes were total oral morphine equivalents (OMEs) filled (mg, median and interquartile range [IQR]) and filling more than 1 prescription within 7 or fewer days after surgery. We estimated associations (adjusted risk ratios [RRs] and 95% confidence intervals [CIs]) between study variables and outcomes in multivariable models. We used a random intercept for each unique prescriber to account for provider-level clustering. RESULTS: Of the 84 369 patients who underwent same-day breast surgery, 72% (n = 60 620) filled an opioid prescription. Median OMEs filled increased with invasiveness (P ± axilla = 135 [IQR 90-180] mg; T ± axilla = 135 [IQR 100-200] mg; R ± axilla = 150 [IQR 113-225] mg, bilateral surgery = 150 [IQR 113-225] mg; p < 0.0001). Factors associated with filling more than 1 opioid prescription were age 30-59 years (v. age 18-29 yr), increased invasiveness (RR 1.98, 95% CI 1.70-2.30 bilateral v. P ± axilla), Charlson Comorbidity Index ≥ 2 versus 0-1 (RR 1.50, 95% CI 1.34-1.69) and malignancy (RR 1.39, 95% CI 1.26-1.53). INTERPRETATION: Most patients undergoing same-day breast surgery fill an opioid prescription within 7 days. Efforts are needed to identify patient groups where opioids may be successfully minimized or eliminated.

Conformers of cysteine and cysteine sulfenic acid and mechanisms of the reaction of cysteine sulfenic acid with 5,5-dimethyl-1,3-cyclohexanedione (dimedone).

Equilibrium and molecular structures, relative energies of conformers of gaseous cysteine (Cys, C, Cys-SH) and gaseous cysteine sulfenic acid (Cys-SOH), and the mechanisms of the reaction of Cys-SOH with 3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one, the enol tautomer of 5,5-dimethyl-1,3-cyclohexadione (dimedone), have been studied using BD(T), CCSD(T), and QCISD(T) with the cc-pVTZ basis set and using MP2 and the density functionals B3LYP, B3PW91, PBE1PBE, PBEh1PBE, M062X, CAM-B3LYP, and WB97XD with the 6-311+G(d,p) basis set. The structures of the six lowest energy conformers of gaseous Cys-SOH are compared with the six lowest energy conformers of gaseous cysteine (Cys-SH). The relative stability of the six lowest energy conformers of Cys-SH and Cys-SOH are influenced by the interplay among many factors including dispersive effects, electronic effects, electrostatic interactions, hydrogen bonds, inductive effects, and noncovalent interactions. The mechanism of the addition of the lowest energy conformer of cysteine sulfenic acid (Cys-SOH) to dimedone may proceed through a six-membered ring transition state structure and through cyclic hydrogen-bonded transition state structures with one water molecule (8-membered ring), with two water molecules (10-membered ring), and with three water molecules (12-membered ring). Inclusion of one and two water molecules in the transition state structures lowers the activation barrier, whereas inclusion of a third water molecule raises the activation barrier.