Association of Opioid Type With Opioid Consumption After Surgery.

OBJECTIVE: This study was designed to test the hypothesis that patients prescribed hydrocodone consume a similar number of tablets as those prescribed oxycodone after surgery. SUMMARY OF BACKGROUND DATA: In October 2017, the Michigan Opioid Prescribing Engagement Network released opioid prescribing guidelines for surgeries. For each procedure, these guidelines recommended prescribing 50% more tablets of hydrocodone than tablets of oxycodone to adjust for potency differences. These guidelines were simplified in January 2019 to recommend the same number of 5 mg hydrocodone tablets as 5 mg oxycodone tablets for each procedure. METHODS: Retrospective, observational analysis of opioid-naïve adults who underwent surgical procedures across 64 hospitals in Michigan and were prescribed 5 mg tablets of hydrocodone or oxycodone between January 1, 2018 and May 31, 2019. The primary outcome was number of tablets consumed. We defined a meaningful difference in consumption as 5 pills a priori. Secondary outcomes included self-reported pain, satisfaction, and opioid refills. RESULTS: A total of 6842 patients were included. Adjusting for covariates, patients prescribed hydrocodone consumed 7 tablets (95% confidence interval 6.79-7.18) while patients prescribed oxycodone consumed 6 tablets (95% confidence interval 5.58-6.40.) Comparing patients prescribed oxycodone with those prescribed hydrocodone, there were no differences in satisfaction, pain, or refills. CONCLUSIONS: Although patients prescribed hydrocodone consumed more tablets than patients prescribed oxycodone, this difference was not clinically significant and did not result in differences in satisfaction, pain, or refills. Perioperative opioid prescribing guidelines may recommend the same number of 5 mg oxycodone and hydrocodone tablets without sacrificing patient-reported outcomes.

The histone H3-H4 tetramer is a copper reductase enzyme.

Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3' dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- and gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.

Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases.

To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.

Primary care physicians' perceptions of rates of unintended pregnancy.

BACKGROUND: Primary care physicians (PCPs) treat many women of reproductive age who need contraceptive and preconception counseling. STUDY DESIGN: To evaluate perceptions of rates of unintended pregnancy, we distributed an online survey in 2009 to 550 PCPs trained in General Internal Medicine or Family Medicine practicing in Western Pennsylvania, Central Pennsylvania, Rhode Island or Oregon. RESULTS: Surveys were completed by 172 PCPs (31%). The majority (54%) of respondents underestimated the prevalence of unintended pregnancy in the United States [on average, by 23±8 (mean±SD) percentage points], and 81% underestimated the risk of pregnancy among women using no contraception [on average, by 35±20 (mean±SD) percentage points]. PCPs also frequently underestimated contraceptive failure rates with typical use: 85% underestimated the failure rate for oral contraceptive pills, 62% for condoms and 16% for contraceptive injections. PCPs more often overestimated the failure rate of intrauterine devices (17%) than other prescription methods. In adjusted models, male PCPs were significantly more likely to underestimate the rate of unintended pregnancy in the United States than female PCPs [adjusted odds ratio (95% confidence interval): 2.17 (1.01-4.66)]. CONCLUSIONS: Many PCPs have inaccurate perceptions of rates of unintended pregnancy, both with and without use of contraception, which may influence the frequency and the content of the contraceptive counseling they provide.