Evaluation of a novel metric for personalized opioid prescribing after hospitalization.

BACKGROUND: The duration of an opioid prescribed at hospital discharge does not intrinsically account for opioid needs during a hospitalization. This discrepancy may lead to patients receiving much larger supplies of opioids on discharge than they truly require. OBJECTIVE: Assess a novel discharge opioid supply metric that adjusts for opioid use during hospitalization, compared to the conventional discharge prescription signature. DESIGN, SETTING, & PARTICIPANTS: Retrospective study using electronic health record data from June 2012 to November 2018 of adults who received opioids while hospitalized and after discharge from a single academic medical center. MEASURES & ANALYSIS: We ascertained inpatient opioids received and milligrams of opioids supplied after discharge, then determined days of opioids supplied after discharge by the conventional prescription signature opioid-days ("conventional days") and novel hospital-adjusted opioid-days ("adjusted days") metrics. We calculated descriptive statistics, within-subject difference between measurements, and fold difference between measures. We used multiple linear regression to determine patient-level predictors associated with high difference in days prescribed between measures. RESULTS: The adjusted days metric demonstrates a 2.4 day median increase in prescription duration as compared to the conventional days metric (9.4 vs. 7.0 days; P<0.001). 95% of all adjusted days measurements fall within a 0.19 to 6.90-fold difference as compared to conventional days measurements, with a maximum absolute difference of 640 days. Receiving a liquid opioid prescription accounted for an increased prescription duration of 135.6% by the adjusted days metric (95% CI 39.1-299.0%; P = 0.001). Of patients who were not on opioids prior to admission and required opioids during hospitalization but not in the last 24 hours, 325 (8.6%) were discharged with an opioid prescription. CONCLUSIONS: The adjusted days metric, based on inpatient opioid use, demonstrates that patients are often prescribed a supply lasting longer than the prescription signature suggests, though with marked variability for some patients that suggests potential under-prescribing as well. Adjusted days is more patient-centered, reflecting the reality of how patients will take their prescription rather than providers' intended prescription duration.

UC Care Check-A Postoperative Neurosurgery Operating Room Checklist: An Interrupted Time Series Study.

BACKGROUND: The effectiveness of neurosurgical operating room (OR) checklists to improve communication, safety attitudes, and clinical outcomes is uncertain. PURPOSE: To develop, implement, and evaluate a post-operative neurosurgery operating room checklist. METHODS: Four large academic medical centers participated in this study. We developed an evidence-based checklist to be performed at the end of every adult-planned or emergent surgery in which all team members pause to discuss key elements of the case. We used a prospective interrupted time series study design to assess trends in clinical and cost outcomes. Safety attitudes and communication among OR providers were also assessed. RESULTS: There were 11,447 neurosurgical patients in the preintervention and 10,973 in the postintervention periods. After implementation, survey respondents perceived that postoperative checklists were regularly performed, important issues were communicated at the end of each case, and patient safety was consistently reinforced. Observed to expected (O/E) overall mortality rates remained less than one, and 30-day readmission rate, length of stay index, direct cost index, and perioperative venous thromboembolism and hematoma rates remained unchanged as a result of checklist implementation. CONCLUSION: A neurosurgical checklist can improve OR team communication; however, improvements in safety attitudes, clinical outcomes, and health system costs were not observed.

The Impact of Unmet Communication and Education Needs on Neurosurgical Patient and Caregiver Experiences of Care: A Qualitative Exploratory Analysis.

OBJECTIVE: To describe neurosurgical patient and caregiver perceptions of provider communication, the impact of patient education, and their understanding of information given to them throughout the neurosurgical care trajectory. METHODS: We organized focus groups composed of patients who had been hospitalized on the neurosurgical service at 5 urban academic tertiary referral hospitals within a large university health system, along with the patients' caregivers. During focus groups, we used semistructured questions to answer the study questions. Content analysis was used to analyze the data. RESULTS: Forty-three patients and caregivers took part in 5 focus groups. In total we identified 12 coding categories (or topics) that were associated with patient and family information needs. Despite the fact all patients were receiving care within the same health system, often with the same care team and clinical environments, their experiences often could not have been more different. We found stark variations in how patients and caregivers described the quality of communication and patient education they received that affected their satisfaction. Satisfied patients and caregivers generally felt well informed and reported good understanding of the clinical care plan throughout the perioperative course, whereas dissatisfied patients struggled with unanswered questions, unmet information needs, and a sense of confusion throughout their care experience. CONCLUSIONS: Our study describes several unmet needs, finds inconsistencies in how information is delivered and a lack of patient-centered and caregiver-centered approaches to communication. Neurosurgery groups should identify unmet needs at their institution and implement strategies and interventions to improve the patient and caregiver experience.

Changing Operating Room Culture: Implementation of a Postoperative Debrief and Improved Safety Culture.

BACKGROUND: Patient safety is foundational to neurosurgical care. Postprocedural "debrief" checklists have been proposed to improve patient safety, but data about their use in neurosurgery are limited. Here, we implemented an initiative to routinely perform postoperative debriefs and evaluated the impact of debriefing on operating room (OR) safety culture. METHODS: A 10-question safety attitude questionnaire (SAQ) was sent to neurosurgical OR staff at a major academic medical center before and 18 months after the implementation of a postoperative debriefing initiative. Rates of debrief compliance and changes in attitudes before and after the survey were evaluated. The survey used a Likert scale and analyzed with standard statistical methods. RESULTS: After the debrief initiative, the rate of debriefing increased from 51% to 86% of cases for the neurosurgery service. Baseline SAQ responses found that neurosurgeons had a more favorable perception of OR safety than did anesthesiologists and nurses. After implementation of the postoperative debriefing process, perceptions of OR safety significantly improved for neurosurgeons, anesthesiologists, and nurses. Furthermore, the disparity between nurses and surgeons was no longer significant. After debrief implementation, neurosurgical OR staff had improved perceptions of patient safety compared with surgical services that did not commonly perform debriefing. Debriefing identified OR efficiency concerns in 26.9% of cases, and prevention of potential adverse events/near misses was reported in 8% of cases. CONCLUSIONS: Postoperative debriefing can be effectively introduced into the OR and improves the safety culture after implementation. Debriefing is an effective tool to identify OR inefficiencies and potential adverse events.

Preventing Delays in First-Case Starts on the Neurosurgery Service: A Resident-Led Initiative at an Academic Institution.

OBJECTIVE: On-time starts for the first case of the day are critical to maintaining efficiency in operating rooms (ORs). We studied whether a resident-led initiative to ensure on-time site marking and documentation of surgical consent could lead to improved first-case start time. DESIGN AND SETTING: In a resident-led initiative at a large 600-bed academic hospital with 25 ORs, we aimed to complete site marking and surgical consents half an hour before the scheduled start time for all first-case neurosurgical patients. We monitored the occurrence of delayed first starts and the length of delay during our initiative, and compared these cases to neurosurgical cases 3 months before the implementation of the initiative and to first-start nonneurosurgical cases. RESULTS: In the year of the initiative, both site marking and surgical consents were completed 30 minutes before the case start in 97% of neurosurgical cases. The average delay across all first-case starts was reduced to 7.17 minutes (N = 1271), compared with 9.67 minutes before the intervention (N = 345). During the study period, non-neurosurgical cases were delayed on average 10.3 minutes (N = 3592). There was a significant difference in latencies between the study period and the period before the initiative (p < 0.001), and also between neurosurgical cases and nonneurosurgical cases (p < 0.001). There was no reduction in delay times seen on the non-neurosurgical services in the study period when compared to the case 3 months before. Considering its effect across 1271 cases, this initiative over 1 year resulted in a total reduction of 52 hours and 57 minutes in delays. CONCLUSIONS: Through a resident-led quality improvement program, neurosurgical trainees successfully reduced delays in first-case starts on a surgical service. Engaging physician trainees in quality improvement and enhancing OR efficiency can be successfully achieved and can have a significant clinical and financial effect.

Improving patient safety in neurologic surgery.

The delivery of safe healthcare is one of the fundamental tenets of medicine, but the study of patient safety has lagged in neurosurgery. Patients are at high risk for medical errors, adverse events, and complications. To prevent and mitigate these risks, it is not enough to shame and blame individual practitioners for mistakes or errors. Complete health care delivery systems should be evaluated for ways to reduce adverse events and errors, and restrict the harm they cause. This article reviews the context of patient safety in history, and outlines the ways in which patient safety is being improved.

Quality improvement tools and processes.

The Model for Improvement and the Plan-Do-Study-Act cycle is a popular quality improvement (QI) tool for health care providers to successfully lead QI projects and redesign care processes. This tool has several distinct components that must be addressed in sequence to organize and critically evaluate improvement activities. Unlike other health sciences clinical research, QI projects and research are based on dynamic hypotheses that develop into observable, serial tests of change with continuous collection and feedback of performance data to stakeholders.

Medical errors in neurosurgery.

BACKGROUND: Medical errors cause nearly 100,000 deaths per year and cost billions of dollars annually. In order to rationally develop and institute programs to mitigate errors, the relative frequency and costs of different errors must be documented. This analysis will permit the judicious allocation of scarce healthcare resources to address the most costly errors as they are identified. METHODS: Here, we provide a systematic review of the neurosurgical literature describing medical errors at the departmental level. Eligible articles were identified from the PubMed database, and restricted to reports of recognizable errors across neurosurgical practices. We limited this analysis to cross-sectional studies of errors in order to better match systems-level concerns, rather than reviewing the literature for individually selected errors like wrong-sided or wrong-level surgery. RESULTS: Only a small number of articles met these criteria, highlighting the paucity of data on this topic. From these studies, errors were documented in anywhere from 12% to 88.7% of cases. These errors had many sources, of which only 23.7-27.8% were technical, related to the execution of the surgery itself, highlighting the importance of systems-level approaches to protecting patients and reducing errors. CONCLUSIONS: Overall, the magnitude of medical errors in neurosurgery and the lack of focused research emphasize the need for prospective categorization of morbidity with judicious attribution. Ultimately, we must raise awareness of the impact of medical errors in neurosurgery, reduce the occurrence of medical errors, and mitigate their detrimental effects.

Frequency and predictors of complications in neurological surgery: national trends from 2006 to 2011.

OBJECT: Surgical complications increase the cost of health care worldwide and directly contribute to patient morbidity and mortality. In an effort to mitigate morbidity and incentivize best practices, stakeholders such as health insurers and the US government are linking reimbursement to patient outcomes. In this study the authors analyzed a national database to determine basic metrics of how comorbidities specifically affect the subspecialty of neurosurgery. METHODS: Data on 1,777,035 patients for the years 2006-2011 were acquired from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as "neurological surgery." Univariate statistics were calculated using the chi-square test, and 95% confidence intervals were determined for the resultant risk ratios. A multivariate model was constructed using significant variables from the univariate analysis (p < 0.05) with binary logistic regression. RESULTS: Over 38,000 neurosurgical cases were analyzed, with complications occurring in 14.3%. Cranial cases were 2.6 times more likely to have complications than spine cases, and African Americans and Asians/Pacific Islanders were also at higher risk. The most frequent complications were bleeding requiring transfusion (4.5% of patients) and reoperation within 30 days of the initial operation (4.3% of patients), followed by failure to wean from mechanical ventilation postoperatively (2.5%). Significant predictors of complications included preoperative stroke, sepsis, blood transfusion, and chronic steroid use. CONCLUSIONS: Understanding the landscape of neurosurgical complications will allow better targeting of the most costly and harmful complications of preventive measures. Data from the ACS NSQIP database provide a starting point for developing paradigms of improved care of neurosurgical patients.

Targeted reduction in neurosurgical laboratory utilization: resident-led effort at a single academic institution.

OBJECT: Given economic limitations and burgeoning health care costs, there is a need to minimize unnecessary diagnostic laboratory tests. METHODS: The authors studied whether a financial incentive program for trainees could lead to fewer unnecessary laboratory tests in neurosurgical patients in a large, 600-bed academic hospital setting. The authors identified 5 laboratory tests that ranked in the top 13 of the most frequently ordered during the 2010-2011 fiscal year, yet were least likely to be abnormal or influence patient management. RESULTS: In a single year of study, there was a 47% reduction in testing of serum total calcium, ionized calcium, chloride, magnesium, and phosphorus. This reduction led to a savings of $1.7 million in billable charges to health care payers and $75,000 of direct costs to the medical center. In addition, there were no significant negative changes in the quality of care delivered, as recorded in a number of metrics, showing that this cost savings did not negatively impact patient care. CONCLUSIONS: Engaging physician trainees in quality improvement can be successfully achieved by financial incentives. Through the resident-led quality improvement incentive program, neurosurgical trainees successfully reduced unnecessary laboratory tests, resulting in significant cost savings to both the medical center and the health care system. Similar programs that engage trainees could improve the value of care being provided at other academic medical centers.

Changing our culture to advance patient safety: the 2013 AANS Presidential Address.

"Changing our culture to advance patient safety" served as the theme of the 81st Annual Meeting of the American Association of Neurological Surgeons and is an issue of personal importance to the author. To improve outcomes for patients and prevent avoidable surgical errors, neurosurgeons must change the culture that currently exists in the operating room so that safety concerns are of the utmost importance and that each member of the care team has a personal sense of accountability. Doing this will involve implementing and consistently applying systems-based strategies to ensure an adequate level of safeguards; improving communication with all members of the care team and dismantling authority gradients; and maintaining a well-trained and well-rested workforce.

Creating a culture of safety within operative neurosurgery: the design and implementation of a perioperative safety video.

OBJECT: Surgical and medical errors result from failures in communication and handoffs as well as lack of standardization in clinical protocols and safety practices. Checklists, simulation training, and teamwork training have been shown to decrease adverse patient events and increase the safety culture of surgical teams. The goal of this project was to simplify and standardize perioperative patient safety practices and team communication processes within operative neurosurgery through the creation of an educational safety video targeted at a neurosurgical provider audience. METHODS: A multidisciplinary group consisting of neurosurgeons, anesthesiologists, nurses, neuromonitoring specialists, quality champions, and a professional video production company met over several months in an iterative process to 1) determine the overall objectives of the video, 2) decide on the content and format of the video, 3) modify the proposed content and format based on stakeholder feedback, and 4) record the video and complete final revisions during postproduction. RESULTS: The video was launched within the authors' institution in July 2012 in conjunction with ongoing research projects to study the effects of the video on 1) multidisciplinary providers' knowledge of perioperative safety practices, 2) provider safety attitudes and safety culture in the operating room, and 3) provider behavior in performing predetermined elements of the preoperative timeout and postoperative debrief. CONCLUSIONS: The neurosurgical perioperative safety video can serve as a national model for how quality champions can drive changes in safety culture and provider behavior among multidisciplinary perioperative patient care teams. Ongoing research is being performed to assess the impact of the video on provider knowledge, behavior, and safety attitudes and culture.

Effects of increased overnight supervision on resident education, decision-making, and autonomy.

BACKGROUND: New supervisory regulations highlight the challenge of balancing housestaff supervision and autonomy. To better understand the impact of increased supervision on residency training, we investigated housestaff perceptions of education, autonomy, and clinical decision-making before and after implementation of an in-hospital, overnight attending physician (nocturnist). METHODS: We established a nocturnist program in July 2010 at our academic, tertiary care medical center. We administered pre-surveys and post-surveys of internal medicine residents on night float rotation during the 2010-2011 academic year. We surveyed residents before and after experiencing the nocturnist program. RESULTS: Housestaff reported an increase in the clinical value of the night float rotation (3.95 vs 4.27, P = 0.01) and the adequacy of overnight supervision (3.65 vs 4.30, P < 0.0001) without a change in decision-making autonomy (4.35 vs 4.45, P = 0.44). Trainees agreed that nocturnist supervision positively impacted patient outcomes (3.79 vs 4.30, P = 0.002). Housestaff contacted attendings more frequently for transfers from outside facilities (2.00 vs 3.20, P = 0.006), during adverse events (2.51 vs 3.25, P = 0.04), prior to ordering invasive diagnostics (1.75 vs 2.76, P = 0.004), and prior to vasopressor use (1.52 vs 2.40, P = 0.004). Residents' fear of revealing knowledge gaps and desire to make decisions independently did not change. CONCLUSIONS: Increased overnight supervision enhanced the clinical value of the night float rotation, increased rates of attending contact during critical clinical decision-making, and improved perception of patient care. These changes occurred without a decrease in housestaff's perceived decision-making autonomy.

Patients previously transfused or treated with epoetin alfa at low baseline hemoglobin are at higher risk for subsequent transfusion: an integrated analysis of the Canadian experience.

BACKGROUND: The introduction of recombinant human erythropoietin to the management of anemia in cancer patients has resulted in significant reductions in allogeneic blood transfusions, while at the same time contributing to improvements in quality of life. A recent meta-analysis of five randomized, placebo-controlled trials with patient-level data revealed that, while epoetin alfa was very effective in reducing transfusions compared with placebo, patients who were pretransfused were twice as likely to subsequently be transfused during epoetin alfa treatment. METHODS: To further assess the validity of this rather provocative concept, another integrated analysis was conducted with patient-level data from three Canadian trials, with a combined total of 665 patients receiving epoetin alfa treatments for their cancer- and chemotherapy-induced anemia. RESULTS: Once again, pretransfusion was the most significant baseline predictor of transfusion, with patients that were pretransfused having a significantly greater likelihood of being transfused than their transfusion-naive counterparts. Furthermore, and corroborating previous findings, baseline hemoglobin (Hb) level was again found to be a significant predictor of transfusion, with patients who were treated at a baseline Hb level < 10 g/dl having a higher chance of being transfused than patients in whom epoetin alfa was initiated at baseline Hb levels of 10-11 g/dl. In addition, when the total units transfused in patients receiving epoetin alfa at different baseline Hb levels were analyzed, >85% of the units of blood transfused were received by patients with baseline Hb levels < 10 g/dl. CONCLUSION: These data strongly suggest that early treatment with epoetin alfa could significantly optimize clinical benefit in reducing the use of transfusion in cancer patients receiving chemotherapy.

The pharmacokinetics of erythropoietin in the cerebrospinal fluid after intravenous administration of recombinant human erythropoietin.

OBJECTIVES: Erythropoietin (EPO) was originally described as a regulator of erythropoiesis. Recently, synthesis of EPO and expression of the EPO receptor (EPO-R) have been reported for the central nervous system (CNS). The potential use of EPO to prevent or reduce CNS injury and the paucity of information regarding its entry into the human CNS led us to examine the pharmacokinetics (PK) of recombinant human EPO (r-HuEPO) in the serum and cerebrospinal fluid (CSF). METHODS: Four patients with Ommaya reservoirs were enrolled to facilitate serial CSF sampling. R-HuEPO was given intravenously (IV) in single doses of 40,000 IU or 1,500 IU/kg and in multiple doses of 40,000 IU daily for 3 days. RESULTS: The EPO concentrations in the CSF increased after a period of slow equilibration. Linear first-order distribution kinetics were observed for serum and CSF. The concentration of EPO in the CSF was proportional to the serum concentration of EPO and the permeability of the blood-brain barrier (BBB), as determined by the albumin quotient (QA=[albumin] CSF/[albumin] serum). A rise in the CSF concentration was seen as early as 3 h after IV administration. Peak levels (C(max)) were reached between 9 h and 24 h. After a single dose of 1,500 IU/kg, the Cmax in the CSF ranged from 11 mIU/ml to 40 mIU/ml, and the ratios of CSF/serum Cmax ranged from 3.6x10-4 to 10.2x10-4. The terminal half-life (t1/2) values of EPO in serum and CSF were similar. The t(1/2) of r-HuEPO in the CSF ranged from 25.6 h to 35.5 h after a single dose of 1,500 IU/l. Using these parameters a PK model was generated that predicts the concentration-time profile of EPO in the CSF. CONCLUSIONS: We report that r-HuEPO can cross the human BBB and describe for the first time the PK of EPO in the CSF after IV administration. Our data suggest that the concentration-time profile of EPO in the CSF can be predicted for individual patients if the serum concentration of EPO and the Q(A) are known. This information may be useful in the design of clinical trials to explore the potential therapeutic effects of EPO during CNS injury.

Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy.

PURPOSE: Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer patients receiving chemotherapy increases hemoglobin levels, improves quality of life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated. METHODS: Breast cancer patients (N = 354) receiving chemotherapy were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses, transfusion requirements, and prognostic factors for responses were measured. RESULTS: At week 12, Functional Assessment of Cancer Therapy-Anemia (FACT-An; mean, 2.16 +/- 12.84 for epoetin alfa v -4.43 +/- 13.42 for SOC) and FACT-An fatigue (mean, 1.85 +/- 10.52 for epoetin alfa v -3.55 +/- 11.14 for SOC) change scores were significantly higher in the epoetin alfa group (P < .0001). Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both comparisons). Percentage transfused was significantly lower in the epoetin alfa group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require a dose increase and 28.7% had a dose reduction. CONCLUSION: Epoetin alfa administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin level, and reducing transfusion requirements in breast cancer patients. The high effectiveness observed could be attributed in part to early treatment with epoetin alfa.

Weekly administration of epoetin alfa improves cognition and quality of life in patients with breast cancer receiving chemotherapy.

Patients with breast cancer treated with adjuvant chemotherapy experience not only fatigue and menopausal symptoms but also documented cognitive dysfunction and reduced capacity to carry out activities of daily living. The role of epoetin alfa in improving cognition and functional capacity was assessed in a large randomized trial through patient self-reported outcomes. Patients with breast cancer (N = 354, adjuvant and metastatic) undergoing chemotherapy were randomized in a 1:1 ratio to receive epoetin alfa (40,000 IU once weekly) or the standard of care (SOC). Change in patient-reported Health Utilities Index Mark 3 (HUI3) from baseline to week 12 was compared between the epoetin alfa and SOC groups. In addition, correlations between the disease-nonspecific HUI3 utility scale and the cancer-specific quality of life instrument Functional Assessment of Cancer Therapy-Anemia (FACT-An) and Fatigue subscales were assessed. Epoetin alfa treatment significantly improved HUI3 scores compared with patients receiving SOC (P = 0.036). Three subscales within HUI3 were also significantly better for epoetin alfa-treated patients (emotion, P = 0.048; ambulation, P = 0.048; and cognition, P = 0.02). Moreover, a strong correlation (P = 0.0001) exists between the disease-nonspecific utility scale HUI3 and the disease-specific FACT-An and FACT-Fatigue scales in terms of overall scores and score changes. The findings of the study demonstrate for the first time in patients with breast cancer that epoetin alfa significantly enhances functional well-being, which translates into significantly better utility scores. In addition, epoetin alfa also significantly improved cognitive function of women undergoing chemotherapy, and this could have an important impact on their lives from a societal perspective.

Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebo-controlled study.

OBJECTIVE: The aim of this study was to evaluate the effects of a constant-estrogen, intermittent-progestogen hormone replacement regimen (Ortho-Prefest, Ortho-McNeil Pharmaceutical, Raritan, NJ, USA) on menopausal symptoms measured by the Kupperman Index and on quality of life measured by the Menopause Quality of Life-Intervention questionnaire. DESIGN: This was a randomized, double-blind, placebo-controlled multicenter study of 90 days' duration. Nonhysterectomized, postmenopausal women with vasomotor symptoms and at least 6 months' amenorrhea were eligible. On completion of the placebo-controlled portion of the study, participants could elect to receive active treatment for an additional 90 days. RESULTS: The study enrolled 119 participants, 59 and 60 in the Prefest and placebo groups, respectively. A marked reduction of menopausal symptoms, as measured by the Kupperman Index, was observed in the active treatment group compared with the placebo group after 45 days' treatment (mean reduction, 14.8 v 7.2 points, respectively), which was sustained to day 90 (16.8 v 7.8 points; < 0.001). Similarly, greater improvement in quality of life, as measured by the Menopause Quality of Life summary score, was also observed in the active treatment group for the same period (improvement of up to 1.6 points v 0.7 points; < 0.001). The adverse event profile was unremarkable. Of the 114 participants who received the active treatment, 6 withdrew because of adverse events. CONCLUSIONS: The constant-estrogen, intermittent-progestogen regimen was highly effective in relieving menopausal symptoms and in improving quality of life and was well received by the study participants.