Wide Variation and Overprescription of Opioids After Elective Surgery.

OBJECTIVE: We aimed to identify opioid prescribing practices across surgical specialties and institutions. BACKGROUND: In an effort to minimize the contribution of prescription narcotics to the nationwide opioid epidemic, reductions in postoperative opioid prescribing have been proposed. It has been suggested that a maximum of 7 days, or 200 mg oral morphine equivalents (OME), should be prescribed at discharge in opioid-naïve patients. METHODS: Adults undergoing 25 common elective procedures from 2013 to 2015 were identified from American College of Surgeons National Surgical Quality Improvement Program data from 3 academic centers in Minnesota, Arizona, and Florida. Opioids prescribed at discharge were abstracted from pharmacy data and converted into OME. Wilcoxon Rank-Sum and Kruskal-Wallis tests assessed variations. RESULTS: Of 7651 patients, 93.9% received opioid prescriptions at discharge. Of 7181 patients who received opioid prescriptions, a median of 375 OME (interquartile range 225-750) were prescribed. Median OME varied by sex (375 men vs 390 women, P = 0.002) and increased with age (375 age 18-39 to 425 age 80+, P < 0.001). Patients with obesity and patients with non-cancer diagnoses received more opioids (both P < 0.001). Subset analysis of the 5756 (75.2%) opioid-naïve patients showed the majority received >200 OME (80.9%). Significant variations in opioid prescribing practices were seen within each procedure and between the 3 medical centers. CONCLUSIONS: The majority of patients were overprescribed opioids. Significant prescribing variation exists that was not explained by patient factors. These data will guide practices to optimize opioid prescribing after surgery.

Developing a standardized healthcare cost data warehouse.

BACKGROUND: Research addressing value in healthcare requires a measure of cost. While there are many sources and types of cost data, each has strengths and weaknesses. Many researchers appear to create study-specific cost datasets, but the explanations of their costing methodologies are not always clear, causing their results to be difficult to interpret. Our solution, described in this paper, was to use widely accepted costing methodologies to create a service-level, standardized healthcare cost data warehouse from an institutional perspective that includes all professional and hospital-billed services for our patients. METHODS: The warehouse is based on a National Institutes of Research-funded research infrastructure containing the linked health records and medical care administrative data of two healthcare providers and their affiliated hospitals. Since all patients are identified in the data warehouse, their costs can be linked to other systems and databases, such as electronic health records, tumor registries, and disease or treatment registries. RESULTS: We describe the two institutions' administrative source data; the reference files, which include Medicare fee schedules and cost reports; the process of creating standardized costs; and the warehouse structure. The costing algorithm can create inflation-adjusted standardized costs at the service line level for defined study cohorts on request. CONCLUSION: The resulting standardized costs contained in the data warehouse can be used to create detailed, bottom-up analyses of professional and facility costs of procedures, medical conditions, and patient care cycles without revealing business-sensitive information. After its creation, a standardized cost data warehouse is relatively easy to maintain and can be expanded to include data from other providers. Individual investigators who may not have sufficient knowledge about administrative data do not have to try to create their own standardized costs on a project-by-project basis because our data warehouse generates standardized costs for defined cohorts upon request.

Effect of Surgical Care Team Consistency During Urologic Procedures on Surgical Efficiency and Perioperative Outcomes.

OBJECTIVE: To evaluate the effect of urologic surgical care team consistency on surgical efficiency and patient outcomes. METHODS: Patients undergoing major urologic surgery (prostatectomy, nephrectomy, or cystectomy) at a single institution from 2010 to 2019 were identified. A surgical care team comprised a certified surgical assistant, certified surgical technologist, and circulating nurse. Primary team member status was assigned on a quarterly basis to team members present for the highest proportion of a surgeon's cases. Surgical efficiency outcomes included time to first incision, procedure duration, and turnover time. Perioperative clinical outcomes included hospital length of stay and 30-day readmission and reoperation rates. Outcomes were compared according to team consistency and assessed via univariate and multivariable analyses. RESULTS: Overall, 11,213 surgical procedures were included. Time to first incision, procedure duration, and turnover time were significantly lower in procedures performed with high-consistency teams (2-3 primary members) versus low-consistency teams (0-1 primary members) (all P <.001). After adjusting for patient-related variables, high-consistency teams were significantly associated with decreased time to first incision (estimate, -2.04 minutes; 95% CI, -2.68 to -1.41 minutes; P <.001) and turnover time (estimate, -7.23 minutes; 95% CI, -9.8 to -4.66 minutes; P <.001). For minimally invasive nephrectomy, high-consistency teams were associated with significantly decreased odds of prolonged hospitalization (odds ratio, 0.63; 95% CI, 0.47-0.84; P = .001). For robotic prostatectomy, high-consistency teams were associated with decreased procedure duration (estimate, -4.55 minutes; 95% CI, -7.48 to -1.62 minutes; P = .002). CONCLUSION: Highly consistent surgical care teams were associated with improved surgical efficiency and patient outcomes.

Evaluation of safety and care outcomes after the introduction of a virtual registered nurse model.

OBJECTIVE: To evaluate the impact of a virtual registered nurse (ViRN) model on safety and care outcomes. ViRN is a telemedicine intervention that enables an experienced virtual nurse to assist the in-person care team in providing care to patients. DATA SOURCES AND STUDY SETTING: Electronic health records data were utilized from the Mayo Clinic during the intervention (December 2020-November 2021) and historical periods (December 2018-November 2019). ViRN was implemented on general medical units at the Mayo Clinic Rochester. We used general medical units at the Mayo Clinic Arizona as the comparison group. STUDY DESIGN: This study used a difference-in-differences design to evaluate the impact of ViRN compared to usual care on transfer to the intensive care unit (ICU), inpatient mortality, and length of stay (LOS). We used logistic regression for transfer to the ICU and inpatient mortality and negative binomial regression for LOS. We controlled for demographics, patient interaction with the health system, clinical characteristics, and admission characteristics. We clustered standard errors to account for patients who have multiple admissions during the study period. PRINCIPAL FINDINGS: There were no significant differences for transfer to the ICU (average marginal effect (AME) -0.08 percentage point [95% confidence interval (CI): -1.34, 1.18]), inpatient mortality (AME 0.43 percentage point [95% CI: -0.33, 1.18]), or LOS (AME -0.20 days [95% CI: -0.57, 0.17]). The findings were mostly consistent across the sensitivity analyses. CONCLUSIONS: Our results suggest that ViRN led to similar outcomes as usual care in general medical units. These findings support the potential to develop more advanced models of ViRN at the Mayo Clinic and the dissemination of the ViRN model to other systems. In the context of staffing shortages and other disruptions to the delivery of nursing care, it is critical to understand whether new models like ViRN provide nurse staffing alternatives without negatively affecting outcomes.

Feasibility of Instituting a Clinical Otolaryngology Human Papillomavirus (HPV) Vaccination Program.

OBJECTIVES: To measure baseline human papillomavirus (HPV) vaccination rates among tertiary and community-based Otolaryngology - Head and Neck Surgery (Oto-HNS) clinic patients and to determine risk factors for under-vaccination. METHODS: Retrospective chart review of patients aged 9 to 26 years presenting to an Oto-HNS clinic from 2017 to 2019. Patients were considered complete for HPV vaccination if they received two doses of HPV vaccine with the first dose received before age 15 years or three doses of HPV vaccine otherwise. RESULTS: 8,532 unique patients met the criteria. At the index visit, 3,110 (36.5%) had completed the HPV series, 5,422 (63.5%) were due for one or more doses, with 4,981 (58.4%) eligible for vaccination at the time of their appointment. Of those dues, most (3,148/5,422 or 58%) were past due by age (≥13 years old). Of the 3,148 patients past due, 745 (23.7%) were partially vaccinated and 2,403 (76.3%) were vaccine naïve. Male sex and younger age were both independently associated with incomplete vaccination (p < 0.0001). CONCLUSION: This study demonstrates that the implementation of on-site HPV vaccination has the potential to increase the opportunities for vaccination among vaccine-eligible patients, especially among young males. Otolaryngologists have the potential to provide meaningful preventive services in the fight against HPV-mediated disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:116-123, 2023.

Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia.

Uncontrolled proliferation is a defining feature of the malignant phenotype. Ki67 is a marker for proliferating cells and is overexpressed in many breast cancers. Atypical hyperplasia is a premalignant lesion of the breast (relative risk approximately 4.0). Here, we asked if Ki67 expression could stratify risk in women with atypia. Ki67 expression was assessed immunohistochemically by digital image analysis in archival sections from 192 women with atypia diagnosed at the Mayo Clinic 1/1/67-12/31/91. Risk factor and follow-up data were obtained via study questionnaire and medical records. Observed breast cancer events were compared to population expected rates (Iowa SEER) using standardized incidence ratios (SIRs). We examined two endpoints: risk of breast cancer within 10 years and after 10 years of atypia biopsy. Thirty-two (16.7%) of the 192 women developed breast cancer over a median of 14.6 years. Thirty percent (58) of the atypias had >or=2% cells staining for Ki67. In these women, the risk of breast cancer within 10 years after atypia was increased (SIR 4.42 [2.21-8.84]) but not in those with <2% staining. Specifically, the cumulative incidence for breast cancer at 10 years was 14% in the high Ki67 vs. 3% in the low Ki67 group. Conversely, after 10 years, risk in the low Ki67 group rose significantly (SIR 5.69 [3.63-8.92]) vs. no further increased risk in the high Ki67 group (SIR 0.78 [0.11-5.55]). Ki67 appears to be a time-varying biomarker of risk of breast cancer in women with atypical hyperplasia.

Pseudoangiomatous stromal hyperplasia and breast cancer risk.

BACKGROUND: Pseudoangiomatous stromal hyperplasia (PASH) is a benign localized fibrotic lesion in which clusters of spindle cells form cleftlike spaces, resembling ectatic vessels. Its relationship to breast cancer risk has not been characterized. MATERIALS AND METHODS: Histological presence of PASH was evaluated by review of archival slides in a single institution cohort of women who underwent benign excisional breast biopsy from 1967 to 1991. Relative risks for subsequent breast cancer were estimated using standardized incidence ratios (SIR), comparing the observed number of cancers with those expected based on Iowa SEER data (mean follow-up 18.5 years). RESULTS: PASH was identified in 579 of 9065 biopsies (6.4%). Women with PASH were younger, more likely to have a palpable mass as indication for biopsy, and had less lobular involution compared with those without PASH (all P < 0.001), while they did not differ by family history of breast cancer or degree of epithelial proliferation. Breast cancers occurred in 34 women with PASH (5.9%) and 789 without (8.8%). Women with PASH had lower risk of breast cancer (SIR 1.03, 95% confidence interval [95% CI] 0.71-1.44) than those without PASH (SIR 1.54, 95% CI 1.43-1.65), P = 0.01. Lower levels of breast cancer risk for the PASH group persisted in analyses stratified by age, family history, epithelial proliferation, and involution. The cancers in the PASH group occurred predominantly in the ipsilateral breast more than 5 years after biopsy. CONCLUSIONS: Despite clinical concern generated by palpable density often associated with PASH, this relatively uncommon histological finding does not connote increased risk of subsequent breast cancer.

Lobular involution: localized phenomenon or field effect?

As women age, the lobules in their breasts undergo involution. We have shown that, in women with benign breast disease, progressive involution assessed near the benign lesion is associated with lower breast cancer risk. However, it is unknown whether the extent of involution is variable or uniform across the entire breast. We compared involution across the four quadrants of both breasts for fifteen women undergoing bilateral prophylactic mastectomy. One pathologist classified involution extent as none (0% involuted lobules), mild (1-24%), moderate (25-74%), or complete (> or =75%). We assessed intra-woman concordance using intraclass correlation coefficients (ICCs), kappa coefficients, and pairwise comparisons of agreement. We found strong intra-woman concordance of involution across the eight quadrants of breast tissue (ICC = 0.75, 95% CI 0.59, 0.89). Our study suggests that lobular involution is a homogeneous process, supporting the use of involution measures from a single benign biopsy as a component in breast cancer risk assessment paradigms.

Economic and clinical outcomes of a physician-led continuous quality improvement intervention in the delivery of percutaneous coronary intervention.

OBJECTIVE: To compare clinical and economic outcomes associated with percutaneous coronary intervention (PCI) in cohorts before and after continuous quality improvement (CQI) was instituted. STUDY DESIGN: Observational study. METHODS: Clinical, angiographic, procedural, and outcome data on 1441 pre-CQI and 1760 post-CQI PCIs (performed in 1997 and 1998, respectively) were derived from an institutional PCI registry. Administrative data were used to estimate total procedural and postprocedural costs and length of stay (LOS). Logistic and generalized linear modeling was used to adjust in-hospital clinical and economic outcomes, respectively, for differences in patient characteristics. RESULTS: The 2 cohorts were similar in terms of age, sex, and rate of diabetes. Post-CQI patients more often received intracoronary stents, had urgent PCIs, had a history of prior PCI, and received glycoprotein IIb/IIIa inhibitors. Procedural success without in-hospital complications occurred in 90% of both cohorts and did not differ statistically in adjusted analyses. Compared with patients treated pre-CQI, those treated post-CQI had a reduced adjusted odds ratio for in-hospital death or any myocardial infarction (odds ratio = 0.66; 95% confidence interval = 0.46, 0.95). Models predicted a mean postprocedural LOS difference of 0.8 days (2.8 days pre-CQI vs 2.0 days post-CQI; P <.001) and an average post-CQI cost savings of $5430 (P <.001). CONCLUSION: Physician-led, multidisciplinary practice management efforts were successful at significantly reducing PCI-related costs in an era of rapid technological advances while maintaining and perhaps improving quality of care.

Association Between Atrial Fibrillation and Costs After Myocardial Infarction: A Community Study.

BACKGROUND: The authors sought to estimate incremental economic impact of atrial fibrillation (AF) and the timing of its onset in myocardial infarction (MI) patients. HYPOTHESIS: Concurrent AF and its timing are associated with higher costs in MI patients. METHODS: This retrospective cohort study included incident MI patients from Olmsted County, Minnesota, treated between November 1, 2002, and December 31, 2010. We compared inflation-adjusted standardized costs accumulated between incident MI and end of follow-up among 3 groups by AF status and timing: no AF, new-onset AF (within 30 days after index MI), and prior AF. Multivariate adjustment of median costs accounted for right-censoring in costs. RESULTS: The final study cohort had 1389 patients, with 989 in no AF, 163 in new-onset AF, and 237 in prior AF categories. Median follow-up times were 3.98, 3.23, and 2.55 years, respectively. Mean age at index was 67 years, with significantly younger patients in the no AF group (64 years vs 76 and 77 years, respectively; P < 0.001). New-onset and prior AF patients had more comorbid conditions (hypertension, heart failure, and chronic obstructive pulmonary disease). After accounting for differences in baseline characteristics, we found adjusted median (95% confidence interval) costs of $73 000 ($69 000-$76 000) for no AF; $85 000 ($81 000-$89 000) for new-onset AF; and $97 000 ($94 000-$100 000) for prior AF. Inpatient costs composed the largest share of total median costs (no AF, 82%; new-onset AF, 84%; prior AF, 83%). CONCLUSIONS: Atrial fibrillation frequently coexists with MI and imposes incremental costs, mainly attributable to inpatient care. Timing of AF matters, as prior AF was found to be associated with higher costs than new-onset AF.

Estrogen receptor expression in atypical hyperplasia: lack of association with breast cancer.

Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967 to 1991. The ACIS III (Dako) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared with the Iowa SEER control population. Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity (P < 0.05). ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. We found increasing ER expression in AH with increasing age. ER expression in AH does not further discriminate breast cancer risk in women with atypia.

Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia.

PURPOSE: Accurate breast cancer risk assessment is vital to personalize screening and risk reduction strategies. Women with atypical hyperplasia have a four-fold higher risk of breast cancer. We evaluated the performance of the Tyrer-Cuzick model, which was designed to predict 10-year risk of breast cancer development, in a well-defined cohort of women with atypia. PATIENTS AND METHODS: The Mayo Benign Breast Disease cohort includes 9,376 women who had a benign breast biopsy between 1967 and 1991. Among those, 331 women with atypia were identified by our study pathologists. Risk factor data for the Tyrer-Cuzick model were collated for each woman and used to predict individual risk of developing invasive breast cancer within 10 years. RESULTS: Over a median follow-up of 14.6 years, 64 (19%) of the 331 women developed invasive breast cancer. In the first 10 years after biopsy, 31 women developed invasive breast cancer whereas the Tyrer-Cuzick model predicted 58.9. The observed-to-predicted ratio was 0.53 (95% CI, 0.37 to 0.75). The concordance statistic was 0.540, revealing that the Tyrer-Cuzick model did not accurately distinguish, on an individual level, between women who developed invasive breast cancer and those who did not. CONCLUSION: The Tyrer-Cuzick model significantly overestimated risk of breast cancer for women with atypia, and individual risk estimates showed poor concordance between predicted risk and invasive breast cancer development. Thus, we cannot recommend the use of the Tyrer-Cuzick model to predict 10-year breast cancer risk in women with atypical hyperplasia.

Independent association of lobular involution and mammographic breast density with breast cancer risk.

BACKGROUND: Lobular involution, or age-related atrophy of breast lobules, is inversely associated with breast cancer risk, and mammographic breast density (MBD) is positively associated with breast cancer risk. METHODS: To evaluate whether lobular involution and MBD are independently associated with breast cancer risk in women with benign breast disease, we performed a nested cohort study among women (n = 2666) with benign breast disease diagnosed at Mayo Clinic between January 1, 1985, and December 31, 1991 and a mammogram available within 6 months of the diagnosis. Women were followed up for an average of 13.3 years to document any breast cancer incidence. Lobular involution was categorized as none, partial, or complete; parenchymal pattern was classified using the Wolfe classification as N1 (nondense), P1, P2 (ductal prominence occupying <25%, or >25% of the breast, respectively), or DY (extremely dense). Hazard ratios (HRs) and 95% confidence intervals (CIs) to assess associations of lobular involution and MBD with breast cancer risk were estimated using adjusted Cox proportional hazards model. All tests of statistical significance were two-sided. RESULTS: After adjustment for MBD, having no or partial lobular involution was associated with a higher risk of breast cancer than having complete involution (none: HR of breast cancer incidence = 2.62, 95% CI = 1.39 to 4.94; partial: HR of breast cancer incidence = 1.61, 95% CI = 1.03 to 2.53; P(trend) = .002). Similarly, after adjustment for involution, having dense breasts was associated with higher risk of breast cancer than having nondense breasts (for DY: HR of breast cancer incidence = 1.67, 95% CI = 1.03 to 2.73; for P2: HR of breast cancer incidence = 1.96, 95% CI = 1.20 to 3.21; for P1: HR of breast cancer incidence = 1.23, 95% CI = 0.67 to 2.26; P(trend) = .02). Having a combination of no involution and dense breasts was associated with higher risk of breast cancer than having complete involution and nondense breasts (HR of breast cancer incidence = 4.08, 95% CI = 1.72 to 9.68; P = .006). CONCLUSION: Lobular involution and MBD are independently associated with breast cancer incidence; combined, they are associated with an even greater risk for breast cancer.

Novel breast tissue feature strongly associated with risk of breast cancer.

PURPOSE: Accurate, individualized risk prediction for breast cancer is lacking. Tissue-based features may help to stratify women into different risk levels. Breast lobules are the anatomic sites of origin of breast cancer. As women age, these lobular structures should regress, which results in reduced breast cancer risk. However, this does not occur in all women. METHODS: We have quantified the extent of lobule regression on a benign breast biopsy in 85 patients who developed breast cancer and 142 age-matched controls from the Mayo Benign Breast Disease Cohort, by determining number of acini per lobule and lobular area. We also calculated Gail model 5-year predicted risks for these women. RESULTS: There is a step-wise increase in breast cancer risk with increasing numbers of acini per lobule (P = .0004). Adjusting for Gail model score, parity, histology, and family history did not attenuate this association. Lobular area was similarly associated with risk. The Gail model estimates were associated with risk of breast cancer (P = .03). We examined the individual accuracy of these measures using the concordance (c) statistic. The Gail model c statistic was 0.60 (95% CI, 0.50 to 0.70); the acinar count c statistic was 0.65 (95% CI, 0.54 to 0.75). Combining acinar count and lobular area, the c statistic was 0.68 (95% CI, 0.58 to 0.78). Adding the Gail model to these measures did not improve the c statistic. CONCLUSION: Novel, tissue-based features that reflect the status of a woman's normal breast lobules are associated with breast cancer risk. These features may offer a novel strategy for risk prediction.

Intermittent hemodialysis versus continuous renal replacement therapy for acute renal failure in the intensive care unit: an observational outcomes analysis.

BACKGROUND: Studies have failed to show a survival difference between intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). Comparative cost analyses are limited and fail to control for differences in patient disease severity and comorbid conditions. The authors retrospectively estimated clinical and economic outcomes associated with CRRT and IHD among critically ill patients experiencing acute renal failure (ARF) in 2 tertiary care hospitals in Rochester, Minnesota, between January 1, 2000, and December 12, 2001. METHODS: 161 critically ill patients requiring dialysis for ARF were analyzed. Patient demographics, comorbid conditions, ARF etiology, mode of renal replacement therapy (RRT), renal recovery, and survival were abstracted from medical chart. APACHE II scores at dialysis initiation were calculated. Administrative data tracked length of stay (LOS) and direct medical costs from initiation of RRT to death or intensive care unit (ICU) and hospital discharge. Multivariate modeling was used to adjust outcomes for baseline differences. RESULTS: 84 (52%) of the patients received CRRT and 77 (48%) received IHD. CRRT-treated patients were younger (58 vs 65 years), less likely male (58% vs 77%), had higher APACHE II scores (32 vs 27) with a higher incidence of sepsis (46% vs 30%) and respiratory disease (56% vs 39%), and were less likely to have chronic renal insufficiency (32% vs 49%). With adjustment for differences in baseline patient characteristics, the RRT method did not affect the likelihood of renal recovery, in-hospital survival, or survival during follow-up. Mean adjusted ICU LOS was 9.5 days shorter for IHD-treated than CRRT-treated patients (P< .001), and the adjusted mean difference in hospital and total costs associated with ICU stay was $56,564 and $60 827, in favor of IHD (P< .001). Mean adjusted total costs through hospital discharge were $93 611 and $140,733 among IHD-treated and CRRT-treated patients, respectively (P< .001). CONCLUSIONS: This observational study suggests that costs may significantly differ by mode of RRT despite similar severity-adjusted patient outcomes. Future prospective comparisons of renal replacement modalities will need to include both clinical and economic outcomes.