Pharmacists' perspectives on opioid stewardship challenges.

OBJECTIVE: Pharmacists are in a distinctive position to champion opioid stewardship principles in communications with prescribers and patients. This effort is focused on elucidating perceived barriers to uphold these principles observed in pharmacy practice. DESIGN: Qualitative research study. SETTING: A healthcare system, consisting of inpatient and outpatient settings across several United States (US) states in both rural and academic settings. PARTICIPANTS: Twenty-six pharmacists who represented the study setting in the sole healthcare system. INTERVENTIONS: Five virtual focus groups were conducted with the 26 pharmacists from inpatient and outpatient settings across four states in both rural and academic settings. Trained moderators conducted 1-hour focus group meetings that consisted of a mix of poll and discussion questions. MAIN OUTCOME MEASURE: Participant questions were related to awareness, knowledge, and system issues affecting opioid stewardship. RESULTS: All pharmacists reported their routine follow-up with prescribers when questions or concerns arise but noted workload as a barrier to meticulous review of opioid prescriptions. Participants highlighted best practices, including transparency on the rationale for guideline exceptions to improve the management of after-hours concerns. Suggestions were integration of guidelines into prescriber and pharmacist order review workflows and a more visible prescriber review of prescription drug monitoring programs. CONCLUSIONS: Improvements in communication and transparency of information related to opioid prescribing between pharmacists and prescribers would enhance opioid stewardship. Integration of opioid guidelines into opioid ordering and review would improve efficiency, guideline adherence, and, most importantly, patient care.

Methods for locating the tibio-femoral contact pathway in total knee replacements using marker-based gait analysis and standard radiography.

INTRODUCTION: The purpose of this study was to develop and test techniques for tracking the path of contact between the tibial and femoral total knee replacement components during level over-ground walking. The tibio-femoral path of contact could be an indicator of the in vivo performance of a total knee replacement as an estimator of areas of contact between the implant components. A longer contact path, indicative of more sliding between the implant components during walking, could indicate an implant at risk for increased wear. In addition, the tibio-femoral contact path determines the position and length of the muscle and ligament lever arms about the knee, and can subsequently influence knee contact force calculations. METHODS: Two methods were developed to predict the tibio-femoral contact pathways for total knee replacement devices. Both methods used patient-specific knee kinematics obtained during gait analysis, standard radiographs obtained during clinical follow-ups, and point-clouds of the tibial and femoral bearing surfaces. The validity of the techniques was evaluated with knee wear simulator tests and comparisons to wear scars on postmortem retrieved tibial components. RESULTS: The average total anterior-posterior distance covered by the contact path for ten patients implanted with a total knee replacement was 29.01 mm on the lateral side, and 21.80 mm on the medial side. Both methods for predicting the tibiofemoral contact pathways yielded similar results, and fell within the wear scars of simulator-tested and postmortem retrieved implants. CONCLUSIONS: The methods for predicting the tibio-femoral contact pathway using marker-based gait analysis and standard clinical radiographs are computationally simple, and reliably predict contact path characteristics as evaluated against wear scars from knee wear simulator tests and postmortem retrieved implants.

Collaboration between allergists and pharmacists increases ß-lactam antibiotic prescriptions in patients with a history of penicillin allergy.

BACKGROUND: Over 90% of patients with a history of penicillin allergy have negative penicillin skin tests. Pharmacists are trained to identify and resolve medication-related problems. We hypothesized that collaboration between allergists and pharmacists to identify and evaluate patients with a history of penicillin allergy would increase ß-lactam antibiotic prescription. METHODS: We conducted a prospective observational study in which patients with a history of penicillin allergy were identified and educated at the pharmacy about penicillin allergy and offered an allergist consultation with a penicillin skin test. All patients were followed up to determine which antibiotics were subsequently prescribed. RESULTS: A total of 503 patients were enrolled, and 71 (14%) were evaluated by an allergist. Sixty-seven of these 71 patients (94%) had a negative penicillin skin test. Twenty-nine patients evaluated by an allergist and 205 patients not evaluated were prescribed antibiotics. Patients prescribed antibiotics and evaluated by an allergist were compared to those not evaluated by an allergist, with the following results: 19 of 29 patients (66%) were prescribed a ß-lactam antibiotic compared to 54 of 205 (26%; p < 0.0001); 8 of 29 patients (28%) were prescribed penicillin compared to 7 of 205 (3%; p < 0.0001); 15 of 29 patients (52%) were prescribed a cephalosporin compared to 48 of 205 (23%; p < 0.01), and 10 of 29 patients (34%) were prescribed a non-ß-lactam antibiotic compared with 177 of 205 (86%; p < 0.0001). CONCLUSION: A collaborative effort between allergists and pharmacists can increase ß-lactam antibiotic prescriptions and decrease non-ß-lactam prescriptions in patients with a history of penicillin allergy.

Calreticulin and Hsp90 stabilize the human insulin receptor and promote its mobility in the endoplasmic reticulum.

Elimination of misfolded membrane proteins in the endoplasmic reticulum (ER) affects cell survival and growth and can be triggered by either local physiologic events or disease-associated mutations. Regulation of signaling receptor degradation involves both cytosolic and ER luminal molecular chaperones, but the mechanisms and timing of this process remain uncertain. Here we report that calreticulin (CRT) and Hsp90 exert distinct effects on the stability and cell surface levels of native and misfolded forms of the human insulin receptor (hIR) and a human variant found in type A insulin resistance. CRT was unique in stabilizing the disease variant and in augmenting hIR expression when glycolysis was abrogated. Effects of Hsp90 were independent of receptor tyrosine phosphorylation and did not change levels of downstream signaling kinases. Live cell imaging revealed that movement of the hIR through the ER was accelerated by misfolding or by overexpression of either CRT or Hsp90. Together, our results indicate that both CRT and Hsp90 control expression of hIR at its earliest maturation stages and modulate its movement within the ER before either degradation or cell surface expression.