Healthcare resource utilization of maribavir versus investigator-assigned therapy in transplant recipients with cytomegalovirus infection refractory (with or without genotypic resistance) to prior treatment: Exploratory analysis of the Phase 3 SOLSTICE trial.

BACKGROUND: Cytomegalovirus (CMV), a common post-transplant infection, is associated with increased healthcare resource utilization. In the Phase 3 SOLSTICE trial, maribavir was superior to investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, and cidofovir) for CMV viremia clearance at Week 8 in transplant recipients with confirmed refractory CMV infection with/without resistance. This exploratory analysis evaluated hospital admissions of patients during the SOLSTICE trial. METHODS: Patients were randomized to maribavir (400 mg twice daily) or IAT for an 8-week treatment phase with a 12-week follow-up. After ≥3 weeks of treatment, patients on IAT who met pre-specified criteria could enter a maribavir rescue arm (8-week maribavir treatment, 12-week follow-up). Adjusted hospitalization rates and length of hospital stay (LOS) were estimated using negative binomial models adjusting for the time in the relevant study phase. Subgroup analysis for the maribavir rescue arm was conducted. RESULTS: Overall, 352 patients were randomized (maribavir: 235; IAT: 117); 22 entered the maribavir rescue arm. After adjusting for treatment exposure, patients on maribavir had a 34.8% reduction in hospitalization rate and 53.8% reduced LOS (days/person/year) versus IAT during the treatment phase. No significant differences between treatments were observed during the follow-up phase, although in both arms, hospitalization rates were lower than in the treatment phase. In the maribavir rescue arm, hospitalizations were 60.6% lower on/after maribavir rescue versus pre-rescue treatment (p = 0.008). CONCLUSION: In patients requiring post-transplant CMV treatment, hospitalization rate and LOS were lower for maribavir than IAT, and hospitalization rates were lower on/after maribavir rescue than pre-rescue. Reducing hospitalizations can alleviate the burden on patients and healthcare systems.

Reliability, validity and important difference estimates for the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18).

Objective: To evaluate psychometric performance of the NCCN-FACT Ovarian Cancer Symptom Index-18 (NFOSI-18) in advanced ovarian cancer. Methods: Cross-sectional, observational data from patients receiving treatment for ovarian cancer. Other measures included European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core (EORTC QLQ-C30) and associated ovarian cancer module (EORTC QLQ-OV28) and Work Productivity and Activity Impairment. Internal consistency reliability, construct validity and anchor-based clinically important differences were assessed. Results: 897 patients were analyzed. Reliability was acceptable for all NFOSI-18 scores; construct validity was supported. Twelve anchors sufficiently correlated with NFOSI-18 scores and suggested clinically important differences: NFOSI-18 total score (5-7), disease-related symptoms - physical (3-4), disease-related symptoms - emotional (1), treatment side effects (2) and functional well-being (1-2). Conclusions: Results provide evidence of reliability and validity of NFOSI-18 scores. Generated CIDs will help improve interpretation of between-group treatment differences in clinical trials.

Lay abstract The National Comprehensive Cancer Network Functional Assessment of Cancer Therapy ­ Ovarian Cancer Symptom Index-18 (NFOSI-18) is a questionnaire assessing the health of patients with ovarian cancer. When using such questionnaires, it is important to evidence that they produce consistent scores (referred to as reliability) and are aligned with other assessments of health (referred to as construct validity). It is also important to set guidelines on what constitutes a clinically important difference in scores, so clinicians and researchers can judge how effective new treatments are. This study analyzed data from 897 patients with advanced ovarian cancer, providing evidence of reliability and construct validity. Guidelines for clinically important differences were also provided. The findings support continued use of the NFOSI-18.

Is insurance instability associated with hypertension outcomes and does this vary by race/ethnicity?

BACKGROUND: Stable health insurance is often associated with better chronic disease care and outcomes. Racial/ethnic health disparities in outcomes are prevalent and may be associated with insurance instability, particularly in the context of health insurance reform. METHODS: We examined whether insurance instability was associated with uncontrolled blood pressure (UBP) and whether this association varied by race/ethnicity. We used a retrospective longitudinal observational cohort study of patients diagnosed with hypertension who obtained care within two health systems in Massachusetts. We measured the UBP, insurance instability, and race of 43,785 adult primary care patients, age 21-64 with visits from 1/2005-12/2013. RESULTS: We found higher rates of UBP for blacks and Hispanics at each time point over the entire 9 years. Insurance instability was associated with greater rates of UBP. Always uninsured black patients fared worst, while white and Hispanic patients with consistent public insurance fared best. CONCLUSIONS: Stable insurance of any type was associated with better hypertension control than no or unstable insurance.

Racial Differences in Insurance Stability After Health Insurance Reform.

BACKGROUND: One of the potential benefits of insurance reform is greater stability of insurance and reduced coverage disparities by race and ethnicity. OBJECTIVES: We examined the temporal trends in insurance coverage by racial/ethnic group before and after Massachusetts Insurance Reform by abstracting records across 2 urban safety net hospital systems. RESEARCH DESIGN: We examined adjusted odds of being uninsured and incident rate ratios of gaining and losing insurance over time by race and ethnicity. We used billing records to capture the payer for each episode of care. SUBJECTS: We included data from January 2005 through December 2013 on patients with hypertension between the ages of 21 and 64 years. We compared 4 racial and ethnic groups: non-Hispanic white, non-Hispanic Black, non-Hispanic Asian, and Hispanic. MEASURES: We examined individual patients' insurance coverage status in 6-month intervals. We compared odds of being uninsured in the transition and postinsurance reform period to the prereform period, adjusting for age, sex, comorbidities practice location and education, and income by Census tract. RESULTS: Among 48,291 patients with hypertension, reduction in rates of uninsurance with insurance reform was greater for Hispanic (29.7%), non-Hispanic Black (24.8%), and non-Hispanic Asian (26.8%) than non-Hispanic white (14.9%) patients. The odds of becoming uninsured were reduced in all racial and ethnic groups (odds ratio, 0.27-0.41). CONCLUSIONS: Massachusetts Insurance Reform resulted in stable insurance coverage and a reduction in disparities in insurance instability by race and ethnicity.

Estimation of minimally important differences and responder definitions for EORTC QLQ-MY20 scores in multiple myeloma patients.

OBJECTIVES: Thresholds for the minimally important difference (MID) or responder definition (RD) in health-related quality-of-life (HRQoL) scores are required to interpret the impact of an intervention or change in the trajectory of the condition which is meaningful to patients. This study aimed to establish MID and RD for the European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20). METHODS: A novel mixed-methods approach was applied by utilizing both existing clinical trial data and prospective patient interviews. Anchor-based, distribution-based, and qualitative-based estimates of meaningful change were triangulated to form recommended RDs for each scale of the EORTC QLQ-MY20. Anchor-based MIDs were summarized using weighted correlation. RESULTS: Recommended MIDs were as follows: Disease Symptoms (DS 10 points), Side Effects of Treatment (SE 10 points), Body Image (BI 13 points), and Future Perspective (FP 9 points). Recommended RDs were as follows: DS (16 improvement; 11 worsening), SE (6 improvement; 9 worsening), BI (33 improvement; 33 worsening), and FP (11 improvement; 11 worsening). CONCLUSIONS: The study generated estimates of the MID and RD for each scale of the EORTC QLQ-MY20. Published estimates will enable investigators and clinicians to adopt these as standard for interpretation and for hypothesis testing. Consequently, analyses from trials of different interventions can be more comparable.

Resident participation in laparoscopic Roux-en-Y gastric bypass: a comparison of outcomes from the ACS-NSQIP database.

BACKGROUND: As clinical outcome data are increasingly tied to hospital reimbursement, balancing quality care with training of surgical residents has become critical. We used the ACS-NSQIP database to determine impact of resident participation in laparoscopic gastric bypass on 30-day morbidity and mortality. METHODS: We queried the ACS-NSQIP database from 1/2005 to 12/2012 for laparoscopic gastric bypass, dividing cases between those with or without resident involvement. Univariate and multivariate analyses of intraoperative and postoperative outcomes were assessed. A sub-analysis was performed to address whether different resident training levels affected outcomes. RESULTS: A total of 43,477 laparoscopic gastric bypass cases were available for analysis; 22,189 had resident involvement (resident = R), and 21,288 did not (no resident = NR). Preoperative characteristics were similar between groups. On multivariate analysis, procedures with resident assistance had increased risk of the following complications: superficial site infection (R = 2.1 vs. 1.5 %, p < 0.001), renal failure (R = 0.4 vs. NR = 0.3 %, p = 0.002), urinary tract infection (R = 1.1 vs. 0.9 %, p = 0.027), and sepsis (R = 0.8 vs. NR = 0.6 %, p = 0.019). Increased operative time in the resident group (29 min, p < 0.0001) demonstrated direct linear association with resident trainee level. There was no statistical difference in the incidences of the following: pulmonary embolism, deep venous thrombosis, deep surgical site infection, organ space infection, pneumonia, unplanned intubation, mechanical ventilation >48 h, septic shock, cardiac arrest, return to the operating room, or mortality. CONCLUSION: Resident participation in laparoscopic gastric bypass was associated with statistically significant, but clinically insignificant increase in incidence of superficial site infection, renal failure, readmission rate, and length of stay. Therefore, although resident participation in laparoscopic gastric bypass is associated with significantly increased operative time, it does not lead to increased mortality and has no clinically significant effect on morbidity.

Modelling Health State Utilities as a Transformation of Time to Death in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: When utilities are analyzed by time to death (TTD), this has historically been implemented by 'grouping' observations as discrete time periods to create health state utilities. We extended the approach to use continuous functions, avoiding assumptions around groupings. The resulting models were used to test the concept with data from different regions and different country tariffs. METHODS: Five-year follow-up in advanced non-small cell lung cancer (NSCLC) was used to fit six continuous TTD models using generalized estimating equations, which were compared with progression-based utilities and previously published TTD groupings. Sensitivity analyses were performed using only patients with a confirmed death, the last year of life only, and artificially censoring data at 24 months. The statistically best-fitting model was then applied to data subsets by region and different EQ-5D-3L country tariffs. RESULTS: Continuous (natural) [Formula: see text] and [Formula: see text] models outperformed other continuous models, grouped TTD, and progression-based models in statistical fit (mean absolute error and Quasi Information Criterion). This held through sensitivity and scenario analyses. The pattern of reduced utility as a patient approaches death was consistent across regions and EQ-5D tariffs using the preferred [Formula: see text] model. CONCLUSIONS: The use of continuous models provides a statistically better fit than TTD groupings, without the need for strong assumptions about the health states experienced by patients. Where a TTD approach is merited for use in modelling, continuous functions should be considered, with the scope for further improvements in statistical fit by both widening the number of candidate models tested and the therapeutic areas investigated.

Three-year follow-up and patient-reported outcomes from CheckMate 078: Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer.

OBJECTIVES: In the phase 3 CheckMate 078 study, nivolumab prolonged overall survival (OS) and showed a favorable safety profile versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer (aNSCLC). However, long-term efficacy, safety, and health-related quality of life findings with second-line nivolumab are very limited in Asian patients with previously treated aNSCLC. Here, we report updated clinical data and patient-reported outcomes (PROs) from the phase 3 CheckMate 078 trial with a 3-year minimum follow-up. MATERIALS AND METHODS: Patients with aNSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or unacceptable toxicity. The primary endpoint was OS; secondary endpoints included objective response rate, progression-free survival, safety, and disease-related symptom deterioration assessed using the Lung Cancer Symptom Scale (LCSS) by Week 12. Additional PRO assessments were exploratory endpoints. RESULTS: At ≥ 37.3 months follow-up, 3-year OS rates were 19% with nivolumab and 12% with docetaxel; 30% and 0% of responders remained in response for ≥ 3 years, respectively. Incidence of treatment-related adverse events occurring after 2 years was lower than during the first 2 years. No new treatment-related deaths were reported. By Week 12 of treatment, rates of disease-related symptom deterioration were 32% with nivolumab and 47% with docetaxel. Completion rates for PRO questionnaires were ≥ 80% in both arms. Clinically meaningful and sustained improvements in LCSS Average Symptom Burden Index scores and delayed time to first symptom deterioration were observed with nivolumab against docetaxel. CONCLUSIONS: At 3 years, nivolumab continued to demonstrate survival benefit versus docetaxel, exhibiting improvements in disease-related symptoms and overall health status in a predominantly Chinese patient population with previously treated aNSCLC. No new safety signals were observed. These findings are similar to the global population.

First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1.

INTRODUCTION: In CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs). METHODS: Patients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted. RESULTS: PRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy. CONCLUSIONS: Nivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.

Pitfalls and Unexpected Benefits of an Electronic Hand Hygiene Monitoring System.

BACKGROUND: No single strategy is more effective than proper hand hygiene (HH) in reducing the spread of nosocomial infections. Unfortunately, health care worker compliance with HH is imperfect. We sought to improve HH compliance using an electronic hand hygiene monitoring system (EHHMS) in 2 units to collect unbiased data and provide feedback. METHODS: In this prospective, quasi-experimental study, the Hyginex EHHMS was installed in 2 units at Tufts Medical Center. Ninety-one bracelets were assigned, and electronic data were collected over 8 months. Human observations continued. We compared HH compliance as measured by human observation before, during, and after EHHMS implementation. Pre- and post-implementation surveys were distributed to staff. RESULTS: The number of electronically captured HH compliance observations was small due to infrequent bracelet use after month 2 of the intervention. HH compliance, as determined by human observation, increased by an average of 1.3 percentage points per month (P = .0005). Survey responses revealed negative attitudes about the EHHMS before and after its implementation. CONCLUSIONS: Despite poor EHHMS participation and negative attitudes toward its implementation, HH compliance, as measured by human observation, significantly improved. Hospitals considering implementing an EHHMS should look to refine the intervention to encourage health care worker participation.

The use of patient-specific equipoise to support shared decision-making for clinical care and enrollment into clinical trials.

BACKGROUND: To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient-clinician shared decision-making about care and RCT enrollment, based on "mathematical equipoise." OBJECTIVES: As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis. METHODS: With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making. RESULTS: The KOMET predictive regression model for knee pain had four patient-specific variables, and an r 2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r 2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received. CONCLUSIONS: Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.

Primary Amyloidosis With Renal Involvement: Outcomes in 77 Consecutive Patients at a Single Center.

BACKGROUND: Outcomes in primary amyloid renal patients are of interest as the era of monoclonal antibody therapies begins. PATIENTS AND METHODS: We studied 77 consecutive primary amyloid renal patients (58% men) for renal progression (end stage renal disease [ESRD]), renal response (RR), and overall survival (OS). RESULTS: At diagnosis median age was 63 (range, 35-81) years, estimated glomerular filtration rate 70 mL/min (range, 5-114), difference between involved and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2 and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR. Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months, respectively. Median OS was not reached in this cohort and was not reached from onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR. In those without ESRD at diagnosis, baseline creatinine and absent RR predicted progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR predicted RR. In multivariate Cox regression analysis, cardiac stage and achievement of CR/VGPR predicted OS, enabling construction of a prognostic model. CONCLUSION: Anti-plasma cell therapies provide a definite albeit limited benefit and new approaches to amyloid-related organ dysfunction are needed.