Quantifying patient centered outcomes associated with the use of bilateral endobronchial coil treatment in patients with severe emphysema

Objective: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses.

Methods: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying).

Results: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p?<?.001) on utility (+0.101 and +0.061, respectively). When combined with selected baseline characteristics and time, Coils and Standard of Care (SoC) generated more QALYs than SoC alone in all scenarios, with incremental lifetime benefit ranging from 0.29–0.55 QALYs.

Conclusions: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.     

First-line treatment disruption among post-menopausal women with HR+/HER2– metastatic breast cancer: a retrospective US claims study

Objective: This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2– metastatic breast cancer (mBC) in the US.

Methods: Post-menopausal women with HR+/HER2– mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data.

Results: A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1–42.2%), liver (8.8–17.3%), and lung (8.6–9.5%). Overall, 37.7% (n?=?3,074) of patients receiving endocrine therapy and 86.1% (n?=?1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p?Conclusions: Treatment disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2– mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.     

Effectiveness of denosumab on back pain-related disability and quality-of-life in patients with vertebral fragility fractures

Background: Denosumab is a fully human IgG2 monoclonal antibody that, neutralizing the receptor activator of nuclear factor kappa-Β ligand (RANKL), inhibits the osteoclast-mediated bone resorption. It is yet to be defined if denosumab can reduce osteoporosis-related disability and improve health-related quality-of-life (HRQoL) in patients with fragility fractures.

Objective: To assess the effectiveness of denosumab in reducing back pain related disability and improving HRQoL in osteoporotic post-menopausal women with vertebral fractures.

Research design and methods: A real practice prospective study was carried out, enrolling women over 50 years with a post-menopausal osteoporosis that experienced at least one vertebral fracture receiving subcutaneous denosumab (60?mg, every 6 months), calcium carbonate (500–1000?mg/day) and cholecalciferol (800?IU/day) for 1 year. Back pain related disability was assessed as the primary outcome using the Spine Pain Index (SPI); secondary outcomes were: SF-12 (Physical Health Composite Score, PCS, and Mental Health Composite Score, MCS), and EuroQol-5D (EuroQol-5D-3L index and EuroQol-Visual Analog Scale, EQ-VAS). All outcome measures were assessed at baseline (T0), after 6 months (T1), and after 12 months (T2) of treatment. Trabecular Bone Score (TBS), lumbar spine (LS) and femoral neck (FN) BMD at T0 and T2 were also evaluated.

Results: This study included 140 post-menopausal women, mean age?=?70.60 (SD?=?8.81) years. There were statistically significant differences after 12 months (T2–T0) in all outcomes assessed: SPI (p?<?0.001), SF-12 PCS (p?<?0.001), SF-12 MCS (p?<?0.001), EQ-5D-3L index (p?=?0.039), and EQ-VAS (p?=?0.003). Moreover, there was a significant improvement of both LS BMD (p?<?0.001) and FN BMD (p?<?0.001). No local or systemic adverse events, including new vertebral fractures, osteonecrosis of the jaw and atypical femur fractures, were reported.

Conclusions: The data demonstrated that denosumab was effective in reducing back pain related disability and in improving HRQoL in post-menopausal women with vertebral fractures.     

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer

Abstract

Background:

The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole.     

Defining the role of aromatase inhibitors in the adjuvant endocrine treatment of early breast cancer

ABSTRACT

Background: Over the past few years, data have been published concerning the relative efficacy and safety profiles of tamoxifen and the aromatase inhibitors (AIs) in the adjuvant therapy setting for women with early hormone receptor-positive breast cancer. Recently, debate has centred around trials which have studied primary tamoxifen and AI therapy, switching and equencing strategies and extended adjuvant therapy.

Methods: Here, a group of 24 breast cancer experts review efficacy and safety data from the recent major trials investigating tamoxifen and the third-generation AIs in postmenopausal women, which have challenged the perception of tamoxifen as optimum adjuvant endocrine therapy. Data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, Breast International Group (BIG) 1‐98 study, National Cancer Institute of Canada MA 17 trial, Intergroup Exemestane Study (IES), Italian Tamoxifen Anastrozole (ITA) trial, Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8 and Arimidex-Nolvadex (ARNO) 95 are considered to provide a rational interpretation of the impact of these data on current practice, and to highlight areas where further investigation is needed.

Conclusion: We can be confident that AIs represent superior adjuvant endocrine treatment to tamoxifen in postmenopausal women, either as initial therapy or as an alternative for women who have started adjuvant therapy with tamoxifen. However, there remain issues regarding the best way to use AIs, such as the optimal length of AI treatment and how a sequence of tamoxifen followed by an AI compares with AI monotherapy; these will require further data to resolve.     

Characterization of patients in the European Forsteo Observational Study (EFOS): postmenopausal women entering teriparatide treatment in a community setting

ABSTRACT

Objective: The European Forsteo^* Observational Study (EFOS) study was primarily designed to assess fracture incidence, degree of pain, health-related quality of life (HRQoL) and compliance in women prescribed teriparatide in a community setting. This report describes the design of the study and characteristics of the patients at entry.

Methods: At entry, 1645 postmenopausal women with a diagnosis of osteoporosis and about to initiate teriparatide treatment were enrolled in eight European countries. Baseline data were collected on demographic characteristics, medical and osteoporosis history, disease status, prior use of medications and HRQoL.

Results: The mean (standard deviation [SD]) age of patients was 71.5 (8.4) years, lumbar spine bone mineral density (BMD) T?score was –3.3 (1.2), the mean number of previous fractures reported after 40 years of age was 2.9 (2.0), 70% had two or more vertebral deformities and 91.7% were pre-treated with bisphosphonates. HRQoL, evaluated by the health state value (HSV) (median: 0.59, Q1; Q3: 0.08; 0.71) and visual analogue scale (VAS) (median 50.0, Q1; Q3: 35.0; 69.0) status of the European quality of life questionnaire (EQ?5D) was poor. Extreme problems were reported by 31% of patients for the pain/discomfort dimension, mobility was limited in 69% and anxiety/depression was reported by 57% of patients. Chronic or intermittent back pain was reported by 91% of patients, which occurred every day or almost every day within the last month in 66% of patients.

Conclusions: The post-menopausal women prescribed teriparatide were severely osteoporotic, with a high fracture risk and poor HRQoL, despite previous therapy for osteoporosis. Moderate to severe back pain was very common.     

The biochemical basis of renal osteodystrophy and post-menopausal osteoporosis: a view from the vitamin D system

Summary

The vitamin D endocrine system is now known to play an essential role in the regulation of plasma calcium and phosphorus concentrations and in overall organismal calcium economy. These two basic functions of the vitamin D endocrine system have provided important new insight into several disease states. The two disease states discussed here are the genesis of renal osteodystrophy and of post-menopausal osteoporosis. It seems likely that defects or alternations in the vitamin D system play important roles in the development of these disease states. Successful treatment undoubtedly will involve the vitamin D system and most likely the active form of vitamin D, 1,25-(OH)₂D₃.     

Health-related quality of life during bosutinib (SKI-606) therapy in patients with advanced chronic myeloid leukemia after imatinib failure

Objectives: The tyrosine kinase inhibitor (TKI) bosutinib has demonstrated activity in patients with advanced phase chronic myeloid leukemia (CML), but effects on health-related quality of life (HRQoL) remain unexplored. This study evaluated HRQoL in advanced CML patients receiving bosutinib in an ongoing phase 2 study following resistance or intolerance to prior imatinib therapy.

Methods: This analysis included data from 76 accelerated-phase (AP) and 64 blast-phase (BP) patients resistant/intolerant to prior imatinib with or without prior exposure to other TKIs. Patient-reported HRQoL assessments completed at baseline; weeks 4, 8, and 12; every 12 weeks thereafter; and at treatment completion included the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu); general health status was assessed using the 5-item EuroQol (EQ-5D) instrument and a visual analog scale (VAS).

Results: HRQoL at baseline was somewhat worse in BP versus AP CML patients. There was a significant improvement in the mean FACT-Leu Total scale at weeks 24, 36, and 48 in AP CML patients and at weeks 4, 8, 12, 24, 36, 48, and 96 in BP CML patients compared with baseline. EQ-5D Utility scores were stable throughout treatment in AP CML patients but significantly improved versus baseline in BP CML patients at weeks 4, 8, 12, and 36. Mean VAS scores were significantly improved at weeks 8, 36, and 48 in AP CML patients and at weeks 4, 8, 12, 24, 36, and 96 in BP CML patients. The lack of a comparison group limits attribution of improvements in HRQoL specifically to bosutinib treatment; potential bias due to non-ignorable dropout may limit the ability to generalize these findings to situations where durations of therapy exceed the 96-week follow-up duration of the present study.

Conclusion: These findings suggest that bosutinib therapy is associated with improved HRQoL in advanced phase CML patients.

Clinical trial registration: NCT00261846.     

Synthesis of (substituted benzamidostyryl) l<Emphasis Type="Italic">H</Emphasis>-benzimidazoles and their screening for anti-inflammatory activity

A series of substituted (benzamidostyryl) benzimidazole (3a–r) were synthesized and evaluated for their possible anti-inflammatory and ulcerogenicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Majority of the compounds were active in carrageenan-induced hind paw edema method test and compounds 3b, 3k had shown high potency after 3 and 4 h time intervals (P < 0.001) almost equipotent to the standard drug indomethacin and showed less severity index than it.     

Pharmacist-led motivational interviewing for diabetes medication adherence in a worksite wellness program

ObjectiveThe primary objective was to evaluate the impact of a pharmacist-delivered motivational interviewing (MI) intervention for diabetes medication adherence; the secondary objectives were to assess the changes in clinical outcomes and health-related quality of life (HRQoL).MethodsA quasi-experimental intervention study was conducted with baseline, postintervention, and follow-up data collections. The study duration was 6 months. Pharmacists trained in MI delivered 3 face-to-face encounters using MI-based semistructured conversation tools to address barriers or challenges to medication adherence. A diabetes worksite wellness program (WWP) at a 350-bed regional hospital in the southeastern United States was the setting, and the study participants were WWP employees or dependents (with type 1 diabetes or type 2 diabetes). The primary outcome was a change in self-reported diabetes medication adherence; the secondary outcomes included the changes in clinical indicators (glycated hemoglobin [HbA1c], blood pressure, and depressive symptoms), and HRQoL. The measures included the Medometer, Summary of Diabetes Self-Care Activities–Medication Subscale (SDSCA-MS), Audit of Diabetes-Dependent QoL (ADDQoL-19), and the Short Form–12 (SF-12) health survey.ResultsFifty-three WWP participants enrolled, and 36 completed the full intervention protocol. Medication adherence (through the Medometer) demonstrated statistically significant improvement after the intervention (P = 0.010); the SDSCA-MS score improved, but was not statistically significant. The change in diastolic blood pressure was statistically significant (P = 0.034), but the changes in HbA1c, systolic blood pressure, presence of depressive symptoms, and ADDQoL-19 were not statistically significant. The SF-12 physical component summary (PCS) and mental component summary (MCS) scores were statistically significant: PCS, P = 0.003, and MCS, P = 0.025.ConclusionThe findings from this pilot study support the effectiveness of a pharmacist-delivered, semistructured MI-based intervention for medication adherence in persons with diabetes in a hospital-based WWP. Pharmacists can support patients’ behavior change using MI communication skills to explore salient barriers to medication adherence and to facilitate goal setting to overcome these in encounters aimed at shared clinical and behavioral decision-making.     

Systematic literature review of health-related quality of life among aggressive non-Hodgkin lymphoma survivors

Objective: Studies have shown that a proportion of patients with aggressive non-Hodgkin lymphoma (NHL) treated with standard chemotherapy will have long-term life expectancy comparable to those in the age-adjusted general population. This systematic literature review summarizes current literature regarding health-related quality of life (HRQoL) of long-term (≥2 years) survivors of aggressive NHL.

Methods: Electronic databases (without restriction on years) and abstracts from four major oncology and HRQoL conferences from 2014 to 2017 were searched. Studies were included if HRQoL or health utility was assessed at least 2 years after NHL diagnosis. Studies focusing on central nervous system lymphoma, or indolent NHL, were excluded. Results were categorized relative to baseline (improvement, deterioration or no change) and compared to the general population (better, comparable or worse).

Results: Fourteen studies met the inclusion criteria. Twelve studies included ≥1 HRQoL instrument, and two measured health utilities using EQ-5D. Half of the studies showed improvement (5/10) and half no change (5/10) in overall HRQoL. Compared to the general population, overall HRQoL was more comparable when assessed at ≥3 years from baseline (3/3 better or comparable) versus assessment at <3 years (2/3 better or comparable). Six studies reported on the physical HRQoL domain with improvement in 4/6 studies and no change in 2/6 studies.

Conclusions: HRQoL of NHL survivors may improve from baseline and becomes more comparable to general population HRQoL with longer survival. Overall HRQoL improvement is driven mostly by improvements in the physical domain.     

A survey of care pathway and health-related quality of life impact for children with central precocious puberty

Abstract

Objective: To describe the timeline to diagnosis for children with central precocious puberty (CPP) and evaluate their psychosocial and health-related quality of life (HRQoL).

Methods: A cross-sectional survey was used to prospectively collect data from caregivers, recruited via the MAGIC Foundation, of children with CPP. The control (non-CPP) group was recruited from a national panel of parents/caregivers. After completing a screening survey, respondents completed a burden of illness survey. Respondents in both groups completed the Pediatric Quality of Life Inventory (PedsQL) and Patient-Reported Outcomes Measurement Information System (PROMIS) peer relationship instruments.

Results: Responses from 142 caregivers of children with and 300 without CPP were assessed. Mean time to treatment after a child’s visit to the pediatric endocrinologist was 220?days and time from onset of symptoms to initiating treatment was approximately 2?years. Responses to HRQoL inventories were all lower in children with CPP versus non-CPP. Adjusted mean (± standard error) PedsQL total (65.3?±?1.8 versus 75.7?±?1.2), Psychosocial Health Summary (62.4?±?1.8 versus 73.4?±?1.2), and Physical Health Summary (70.7?±?2.2 versus 79.9?±?1.5) scores were significantly lower (p?<?.01) in CPP versus non-CPP group. PROMIS peer relationship T score (± standard error) was numerically lower for the CPP versus non-CPP group (45.4?±?1.0 versus 47.4?±?0.7, p = .11).

Conclusions: In clinical practice, there is a longer than expected delay between CPP symptom onset and referral to an endocrinologist and ultimate treatment. Children with CPP experience a substantial disease burden with a significant impact on emotional, social, and physical functioning compared with children without CPP.     

Investigations on the estrogenic activity of the metallohormone cadmium in the rat intestine

Cadmium (Cd), a toxic heavy metal and an important environmental pollutant, is now also regarded as potential endocrine disruptor. Its estrogenic effects have been examined so far just in classical target tissues, e.g. uterus, and mostly upon intraperitoneal (i.p.) injection of CdCl₂. Yet, estrogen receptors are also expressed in the gut, and food is the main source of cadmium intake in the general population. Therefore, possible estrogenic effects were now investigated in the intestine of ovariectomized Wistar rats after oral short- and long-term administration of CdCl₂ (0.05–4 mg/kg bw on 3 days by gavage and 0.4–9 mg/kg bw for 4 weeks in drinking water) or upon i.p. injection (0.00005–2 mg CdCl₂/kg bw), and compared to steroid estrogen (estradiol or ethinylestradiol) treated groups. Analysis of Cd in kidneys and small intestine by atomic absorption spectrometry showed dose-dependent increases in tissue levels with rather high Cd concentrations in the gut, both after oral and i.p. administration. Expression of metallothionein (MT1a), a typical metal response parameter, was clearly induced in kidney and small intestine of several CdCl₂ treated groups, but also notably increased by steroid estrogens. Levels of estrogen-regulated genes, i.e. pS2/TFF1, vitamin D receptor (VDR), and estrogen receptor α and β (ER α/β) were studied as parameters of hormonal activity: The intestinal mRNA expression of pS2/TFF1 was significantly decreased in the estrogen reference groups, but also after single i.p. injection and oral long-term administration of CdCl₂. In contrast, the mRNA and protein expression of the VDR were unaffected by long-term administration of Cd via drinking water. We detected expression of ERβ, but not ERα in the small intestine of OVX rats. ERβ mRNA and protein expression were significantly down-regulated by Cd, similar to the ethinylestradiol reference group. The mRNA expression and immunostaining of proliferating cell nuclear antigen (PCNA), as an index for cell proliferation, revealed decreases after long-term administration of Cd and ethinylestradiol. In summary, cadmium exposure was shown to modulate molecular and functional parameters of estrogenicity in the intestinal tract of OVX rats. As the intestine is known to express predominantly ERβ, and is an important site of interaction with dietary contaminants, it is indicated to further investigate specific molecular mechanisms of cadmium and estrogen receptor interactions in more detail.     

Impact of a pharmacist-driven recombinant zoster vaccine administration program

ObjectiveTo determine whether a pharmacist-driven recombinant zoster vaccine (RZV) administration pilot program within a human immunodeficiency virus/infectious diseases clinic setting increased the completion of the 2-dose series when compared with standard care.MethodsIn this retrospective cohort study, the patients enrolled in a pharmacist-driven RZV administration pilot program (intervention) were compared with those in provider-directed RZV education (standard care) for completion of the 2-dose vaccine series.ResultsOne hundred nineteen patients were included (standard care [n = 84], intervention intention to treat [ITT, n = 35], and intervention modified ITT [mITT, n = 23]). There was increased completion of the 2-dose vaccine series in the intervention cohort compared with the standard care cohort (ITT 66% and mITT 100% vs. 23%; P < 0.001).ConclusionThe pharmacist-driven RZV administration program resulted in increased completion of the 2-dose series. However, the revenue generated did not justify the cost of a pharmacist salary for the allocated time commitment.     

Breast Cancer Chemoprevention-An Update

Summary

This article reviews the recent findings of the IBIS-1 and ATAC trials regarding the role of tamoxifen and anastrozole in the chemoprevention of breast cancer. It also emphasises the need to individualise chemoprevention strategies, and to identify high-risk women who are most likely to develop oestrogen receptor (ER)-positive breast cancer.

The prevention of ER-negative disease requires further research, and is likely to be challenging.     

Solifenacin treatment for overactive bladder in black patients: patient-reported symptom bother and health-related quality of life outcomes*

ABSTRACT

Objective: Health-related quality of life (HRQoL) data for black patients receiving overactive bladder (OAB) treatment have not been previously reported. This study presents patient-reported outcomes, measured by symptom bother and HRQoL, in black patients participating in an open-label study of solifenacin succinate. Results are presented, as are those from the full study population.

Methods: In the 12-week, VESIcare Open-Label Trial (VOLT), patients received solifenacin 5?mg or 10?mg once daily according to an individualized, flexible-dosing regimen. A post-hoc analysis assessed solifenacin efficacy and safety in blacks (n = 274). Three patient-derived indices served as study endpoints. The Patient Perception of Bladder Condition (PPBC) scale assessed overall symptom bother, a visual analog scale (VAS) recorded individual symptom bother, the Overactive Bladder Questionnaire (OAB-q) measured OAB-related HRQoL.

Results: Blacks reported significant reductions in bladder-related problems based on PPBC scores (?p < 0.001) and improvements in all OAB-q subscales (symptom severity, coping, concern, sleep, social, and HRQoL; p < 0.001). Based on VAS ratings, significant improvements were reported for urinary urgency, urge incontinence, frequency, and nocturia (?p < 0.001 for change from baseline). Although this study was not placebo-controlled and statistical comparisons were not made, results were similar in the full study population. In total, 46% of black patients experienced adverse events (mostly anticholinergic) and 7.6% discontinued treatment as a result.

Conclusions: Solifenacin treatment was perceived as offering relief from symptom bother and improving HRQoL in the black cohort from VOLT. These results are similar to those in the full VOLT population.