Association between bronchiectasis exacerbations and longitudinal changes in FEV1 in patients from the US Bronchiectasis and NTM Research Registry.

BACKGROUND: This study aimed to evaluate the association between the number of non-cystic fibrosis bronchiectasis (bronchiectasis) exacerbations during baseline and follow-up (objective 1) and to identify longitudinal changes in FEV1 associated with exacerbation frequency (objective 2). METHODS: This was a retrospective cohort study of adult patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry September 2008 to March 2020. Objective 1 outcome was association between exacerbations during baseline (24 months) and 0-to-24 month and 24-to-48 month follow-up windows. Objective 2 outcomes were change in FEV1 and FEV1 % predicted over 24 months stratified by baseline exacerbation frequency. RESULTS: Objective 1 cohort (N=520) baseline frequency of any exacerbations was 59.2%. Overall, 71.4% and 75.0% of patients with ≥1 baseline exacerbations had ≥1 exacerbations during the 0-to-24 and 24-to-48 month follow-ups. Having ≥1 exacerbation during baseline was significantly associated with ≥1 exacerbation during the 0-to-24 month (P=0.0085) and 24-to-48 month follow-ups (P=<0.0001). Objective 2 cohort (N=431) baseline FEV1 was significantly lower in patients who had more exacerbations, however decline in FEV1 from baseline was not significantly different between patients with 0, 1, and ≥2 exacerbations. In patients with more baseline exacerbations, FEV1 % predicted was significantly lower at baseline (P<0.0001) and at 12 (P=0.0002) and 24 month follow-ups (P<0.0001). CONCLUSIONS: Patients with frequent bronchiectasis exacerbations may be more likely than those with less frequent exacerbations to experience disease progression based on future exacerbation frequency and lower FEV1 at baseline, although FEV1 decline may not differ by baseline exacerbation frequency.

Pulmonary exacerbations in insured patients with bronchiectasis over 2†years.

Background: Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation. Methods: This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days. Patients with ≥36 months of continuous health plan enrolment (12 months preceding the first bronchiectasis claim, i.e., baseline period and ≥24 months of follow-up) were included. Patients with cystic fibrosis at baseline were excluded. A multivariable logistic regression model identified baseline factors associated with having ≥2 exacerbations over the 2-year follow-up period. Results: In total, 14 798 patients with bronchiectasis were identified; 64.5% were female, 82.7% were aged ≥55 years and 42.7% had ≥2 exacerbations at baseline. Having ≥2 exacerbations after 2 years was positively associated with chronic macrolide use, long-acting ß2 agonist use, gastro-oesophageal reflux disease, heart failure and Pseudomonas aeruginosa. Frequent exacerbations (≥2) at baseline were significantly associated with greater likelihood of experiencing ≥2 exacerbations during the first and second year's follow-up (unadjusted odds ratios 3.35 (95% CI 3.1-3.6) and 2.96 (95% CI 2.8-3.2), respectively). The proportion of patients experiencing ≥1 all-cause hospitalisation cumulatively increased from 41.0% in the first year of follow-up to 51.1% over 2 years' follow-up. Conclusion: Frequent exacerbations in patients with bronchiectasis may increase the likelihood of future exacerbations over 2 years of follow-up, with increased hospitalisation rates over time.

Benefit-risk assessment of brensocatib for treatment of non-cystic fibrosis bronchiectasis.

Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile. https://bit.ly/3SbisW3.

Health state utility estimation of Mycobacterium avium complex pulmonary disease using a time trade-off approach.

AIMS: To obtain appropriate health state utility values for cost-effectiveness analyses of new Mycobacterium avium complex pulmonary disease (MAC-PD) treatments. The impact of MAC-PD severity and symptoms on quality of life (QoL) also were quantified. METHODS: A questionnaire describing four health states, MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative, was developed based on St. George's Respiratory Questionnaire (SGRQ) Symptom and Activity scores from the CONVERT trial. The time trade-off (TTO) method with ping-pong titration procedure was used to estimate health state utilities. Regression analyses assessed the impacts of covariates. RESULTS: Of 319 Japanese adults (49.8% female, mean age 44.8 years), mean (95% CI) health state utility scores (MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative) were 0.252 (0.194-0.310), 0.535 (0.488-0.582), 0.816 (0.793-0.839), and 0.881 (0.866-0.896), respectively. MAC-negative state utility scores were significantly higher than MAC-positive severe (mean difference [95% CI], 0.629 [0.574-0.684]), MAC-positive moderate (0.346 [0.304-0.389]), and MAC-positive mild (0.065 [0.048-0.082]) scores (p < .001 each). Most participants would trade survival duration to avoid MAC-positive states (97.5% to avoid MAC-positive severe; 88.7% MAC-positive moderate; 61.4% MAC-positive mild). Regression analyses to investigate the impact of background characteristics showed similar utility differences between health states when not adjusted for covariates. LIMITATIONS: Some participant demographics differed from the general population; however, this did not impact utility differences among health states as regression analyses adjusting for demographics did not affect these differences. Similar investigations are needed among patients with MAC-PD and in other countries. CONCLUSIONS: This study evaluating the impact of MAC-PD on utilities using the TTO method demonstrates that differences in utilities are dependent on the severity of respiratory symptoms and their impacts on daily activities and QoL. These results could contribute to a better quantification of the value of MAC-PD treatments and improve assessments of cost-effectiveness.

Economic burden of central nervous system metastases in human epidermal growth factor receptor 2-positive breast cancer.

Aim: Compare healthcare resource utilization and costs among patients with HER2+ metastatic breast cancer (MBC) with and without central nervous system (CNS) metastases. Methods: Retrospective matched cohort study using IQVIA's PharMetrics® Plus claims database. Results: Patients with CNS metastases (n = 753) experienced more outpatient, emergency room and inpatient visits versus controls (n = 753; all p < 0.05). In the post-index year, median total all-cause healthcare costs were significantly higher among patients with CNS metastases versus controls ($112,402 vs $50,835; p < 0.0001); outpatient costs primarily drove the cost differential. Conclusion: More effective therapies are needed that improve clinical outcomes and reduce economic burden associated with CNS metastases in patients with HER2+ MBC.

Burden of illness and treatment patterns among patients with peripheral T-cell lymphoma in the US healthcare setting.

OBJECTIVE: Limited real-world information exists on the characteristics or treatment patterns of patients with peripheral T-cell lymphoma (PTCL). We reported demographics, treatments and direct healthcare resource utilization (HRU) in a large cohort of US patients newly diagnosed with PTCL. METHODS: Patients aged ≥18 years with a PTCL diagnosis between January 2011 and December 2016 were identified from the Inovalon MORE2 Registry. Continuous medical/pharmacy enrollment 6-months prior to and ≥1-month after the first PTCL diagnosis was required. The main focus of this study was on newly diagnosed patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus other chemotherapy. RESULTS: A total 2971 patients with PTCL and chemotherapy information were included in the study; 1706 (57%) received CHOP and 1265 (43%) other chemotherapy. A majority of patients (51.7%) were female; mean (standard deviation) age at index was 61.0 (±16.0), Charlson score was 4.1 (±2.9), and follow-up time was 24.6 (±16.7) months. During the variable follow-up period, HRU was similar for the CHOP and other chemotherapy cohorts; 58.1% and 59.3% had ≥1 all-cause hospitalizations, respectively. The proportion of patients with ≥1 PTCL-related hospitalizations was higher in the CHOP than in the other chemotherapy cohort (40.3% vs. 9.7%, respectively) and mean length of stay was longer (4.6 vs. 3.7 days per patient per month, respectively). CONCLUSIONS: This retrospective analysis of patients with PTCL revealed high levels of comorbidity and HRU; novel interventions that improve patient outcomes and reduce the HRU burden of PTCL are needed.

Health Care Resource Utilization and Costs Among Medicare Beneficiaries Newly Diagnosed With Peripheral T-cell Lymphoma: A Retrospective Claims Analysis.

BACKGROUND: There are limited data on the treatment patterns, health care resource utilization (HRU), survival outcomes, and medical costs among Medicare beneficiaries newly diagnosed with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: This was a retrospective analysis of data from the Medicare Fee-For-Service claims database using the 100% sample of the Medicare research identifiable files. Patients identified for analysis were aged ≥ 65 years and had received a PTCL diagnosis between January 2011 and December 2017. Outcomes included patient characteristics, HRU, direct all-cause and PTCL-specific health care costs, treatment patterns, and overall survival. Patients were followed until disenrollment, death, or end of the study period. RESULTS: Overall, 2551 patients with PTCL were included, among whom 37% had ≥ 1 emergency department visit and 42% had ≥ 1 hospitalization during the pre-index period. During follow-up (median, 2.0 years), 70% of patients were hospitalized at least once (mean length of stay, 1.34 days); 22% advanced to hospice care. A total of 1593 patients received ≥ 1 identifiable treatment regimen post index, of whom 26% received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 3% CHOEP (CHOP plus etoposide), whereas 71% received other regimens. The median overall survival among patients receiving identifiable therapy was 4.6 years. The mean adjusted per-person-per-month all-cause costs among the overall PTCL cohort during follow-up were $5930; the mean disease-related costs were $2384. Costs were driven primarily by hospitalizations (38%) and outpatient services (28%). CONCLUSIONS: Medicare beneficiaries newly diagnosed with PTCL have high HRU and cost burden, with no evident standard of care in real-world practice.

Patient preferences for first-line treatment of classical Hodgkin lymphoma: a US survey and discrete choice experiment.

A cross-sectional online survey, including a discrete choice experiment (DCE), was used to investigate first-line treatment preferences in patients with classical Hodgkin lymphoma (cHL) in the United States; 141 patients (median age 35.0 years) participated. In the DCE, risk of progression at 2 years (progression free survival) had the highest relative importance to patients (31.3%) when considering first-line treatments, followed by 2-year overall survival (OS; 26.9%), on-treatment pulmonary toxicity (23.3%), and on-treatment peripheral neuropathy (18.5%). Marginal rate of substitution analyses demonstrated that a 0.44% and 0.09% increase in 2-year OS was required for patients to accept a 1% increase in the risk of disease progression at 2 years and peripheral neuropathy, respectively. A 2.6% increase in 2-year OS was needed to accept a 7% rather than a 2% risk of pulmonary toxicity. In summary, patients with cHL rated survival attributes as more important than drug-related toxicity when considering first-line treatments.

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

BACKGROUND: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION: NCT01578499.

Cost-effectiveness of brentuximab vedotin with chemotherapy in treatment of CD30-expressing PTCL.

OBJECTIVES: To evaluate the cost-effectiveness of brentuximab vedotin (Adcetris) in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in the first-line setting for CD30-expressing peripheral T-cell lymphoma (PTCL). STUDY DESIGN: An economic model was developed using clinical and quality-of-life (QOL) data from the ECHELON-2 trial, in which A+CHP demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). METHODS: A partitioned survival model, consisting of 3 health states (PFS, postprogression survival, and death), was constructed from a US payer perspective over a lifetime time horizon. PFS and OS observed from ECHELON-2 were extrapolated using standard parametric distributions. The best-fitting distributions (log-normal for both arms) were selected based on statistical goodness of fit and clinical plausibility of the long-term projections. Utilities were based on the European Quality of Life 5-Dimensional data collected in ECHELON-2. Medical resource use and costs were from literature and standard sources. RESULTS: The model predicted that A+CHP extended PFS and OS by 2.92 and 3.38 years, respectively, over CHOP. After incorporating QOL and discounting, A+CHP was associated with 1.79 quality-adjusted life-years gained at a total incremental cost of $159,388, resulting in an incremental cost-effectiveness ratio (ICER) of $89,217. Sensitivity analyses provided ICERs ranging approximately from $57,000 to $138,000. The estimated probability that A+CHP is cost-effective compared with CHOP was 82% at a willingness-to-pay threshold of $150,000. CONCLUSIONS: Based on the ECHELON-2 trial data, this analysis found A+CHP to be cost-effective for patients with previously untreated CD30-expressing PTCL.

Patient-reported distress in Hodgkin lymphoma across the survivorship continuum.

PURPOSE: Hodgkin lymphoma (HL) survivors face long-term, elevated risk of treatment-related sequelae, including psychosocial distress associated with poor health outcomes. The magnitude and sources of distress are not well described in the routine care of HL outside of clinical trials. METHODS: We conducted a retrospective cohort study of patients visiting a tertiary-care center for treatment or long-term follow-up of HL. Patient-reported distress was documented using the National Comprehensive Cancer Network Distress Thermometer (DT) and Problem List. Three survivor groups were compared using descriptive methods: on treatment, surviving < 5 years, and surviving ≥ 5 years since diagnosis. RESULTS: A total of 1524 DT were abstracted for 304 patients (106 on treatment, 77 surviving < 5 years, and 121 surviving ≥ 5 years). Distress was low overall (median DT = 1, inter-quartile range 0-4) and was similar across survivor groups. However, actionable distress (score ≥ 4) was reported at 29.5% of clinical encounters. Patients on treatment more frequently reported actionable distress (32.5% of visits) compared with patients surviving < 5 years (20.4%) and ≥ 5 years (28.7%) (P = 0.065). Distress was associated primarily with physical and emotional problems, especially fatigue, worry, and sleep. We did not observe any associations between distress and clinical prognostic factors. CONCLUSIONS: Distress burden is low in HL, but survivorship is marked by periods of actionable distress, largely related to physical symptoms and emotional issues. This burden may be higher when on treatment and is unrelated to disease-related prognostic factors. Survivorship research typically focuses on the post-therapy period, but our results support testing the efficacy of interventions to address distress in HL during active treatment as well.

Real-world analysis of cost, health care resource utilization, and supportive care in Hodgkin lymphoma patients with frontline failure.

PURPOSE: The purpose of this study was to evaluate the economic burden of frontline failure (FLF) among classical Hodgkin lymphoma (HL) patients during and after treatment. PATIENTS AND METHODS: The population consisted of adult HL patients identified from January 2010 through September 2015 without any other primary cancer prior to HL diagnosis, who also had a frontline (FL) regimen indicative of curative intent. Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy. RESULTS: There were 77 FLF and 602 non-FLF patients who met the final inclusion criteria. FLF and non-FLF patients were demographically similar with mean age 38.5 years and 47.5% females. Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, P<0.05). Annual total expenditures were significantly higher among FLF patients (US$198,388) vs non-FLF patients (US$37,549). FLF (vs non-FLF) patients had a significantly shorter duration of FL therapy (116 vs 131 days, P=0.024) and higher total PPPM expenditures during FL (US$29,040 vs US$16,369, P<0.05). Annual cost varied by failure type with those who failed due to restart incurring the highest cost (US$269,189) and those who switched incurring the lowest cost (US$46,951). FLF patients had a significantly greater utilization in every health care resource category during follow-up. CONCLUSION: FLF (vs non-FLF) patients utilized substantially more health care resources and incurred a substantially higher economic burden. Over 5 years, FLF patients with at least two lines of treatment were projected to incur US$535,846 of health care costs. Further research is needed to determine optimal treatment that could reduce the risk of progression, need for treatment after FL, and enhance long-term clinical and economic outcomes.

Development of a harmonized patient-reported outcome questionnaire to assess myelofibrosis symptoms in clinical trials.

Along with reducing spleen size, relieving symptom severity is a key objective of the treatment of myelofibrosis (MF). Several questionnaires have been developed for patient self-report of MF symptoms in clinical trials and each includes unique instructions, items, and/or response scales. This variability in questionnaire content increases uncertainty; it is unclear which questionnaire is the most appropriate for assessing MF symptoms and it makes comparisons across trials difficult. The Patient-Reported Outcome (PRO) Consortium's MF Working Group (WG) was established to review existing MF symptom questionnaires and to develop a harmonized, consensus-based PRO questionnaire for use in future MF trials. The WG focused on the seven core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. The resulting Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) asks respondents to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. The MFSAF v4.0, for which there are 24-h and 7-day recall formats, will be maintained and licensed by the Critical Path Institute and made publicly available for use in future clinical trials.

Robotic retroperitoneal partial nephrectomy: a four-arm approach.

INTRODUCTION: Robotic partial nephrectomy is an effective alternative to laparoscopic partial nephrectomy. The 3-arm and 4-arm transperitoneal robotic approaches are well described in the literature. However, a retroperitoneal robotic technique has yet to be fully described. We report our technique and initial experience with robotic retroperitoneal partial nephrectomy with a novel 4-arm approach. MATERIALS AND METHODS: We reviewed our current experience with the robotic retroperitoneal approach. Descriptive statistics on patient characteristics, operative parameters, and oncologic outcomes are reported. RESULTS: A total of 67 robotic-assisted partial nephrectomies were performed by one surgeon between October 2009 and October 2010. The 4-arm retroperitoneal approach was used in 8 patients (12%) with no complications. Median tumor size was 2cm. All were posterior renal tumors, with 5 located in the upper pole. The median operative time, warm ischemia time, estimated blood loss, and length of stay were 202 minutes, 18 minutes, 100cc, and 2 days, respectively. Pathology indicated renal cell carcinoma (RCC) in 7 patients with negative margins. CONCLUSION: The 4-arm robotic approach to retroperitoneal partial nephrectomy is safe, reproducible, and easily used. The fourth arm provides optimal traction on target tissues in key maneuvers and may decrease complications and positive margins secondary to impaired exposure.

The incidence of fluoroquinolone resistant infections after prostate biopsy--are fluoroquinolones still effective prophylaxis?

PURPOSE: Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquinolone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquinolone resistant infections after prostate biopsy under fluoroquinolone prophylaxis. MATERIALS AND METHODS: We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1 month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was calculated. RESULTS: Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However, 100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone. CONCLUSIONS: Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms, almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or amikacin should be initiated until culture specific therapy can be implemented.

Treatment of splenic injury during laparoscopic nephrectomy with BioGlue, a surgical adhesive.

Splenic laceration is a recognized complication of both open and laparoscopic renal surgery. Laparoscopic renal surgery continues to become the new standard of care, and this potentially problematic complication may be encountered during mobilization to gain access to the retroperitoneum. We present 2 cases of splenic injury managed with BioGlue, a new surgical adhesive, during one hand-assisted and one pure laparoscopic nephrectomy. Application of the BioGlue adhesive resulted in satisfactory hemostasis for both injuries without the need for further intervention. These preliminary observations suggest that BioGlue may be a useful addition to the urologic armamentarium to achieve hemostasis in laparoscopic surgery.