Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France.

BACKGROUND: Midostaurin (MIDO) combined with standard chemotherapy was approved by the European Medicines Agency in 2017 for the treatment of adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) based on results from the RATIFY trial. METHODS: A cost-effectiveness model was developed to compare MIDO and standard-of-care (SOC) to SOC alone in France. Per Haute Autorité de Santé (HAS) guidelines, a partitioned survival model with eight health states was used: diagnosis/induction, complete remission, relapse, hematopoietic stem cell transplantation (HSCT), HSCT recovery, post-HSCT recovery (stabilized after HSCT recovery), post-HSCT relapse, and mortality. A lifetime horizon was used beginning at diagnosis with a "cure model,", which assumed natural mortality after trial cut-off. Utility values were obtained from a systematic literature review and included disutilities. Resource utilization was based on HAS clinical guidelines and a survey of French physicians and included drugs and administration, adverse events, routine medical care, HSCT, and end-of-life care costs. RESULTS: In RATIFY and after extrapolation, MIDO improved survival compared to SOC, translating into MIDO-treated patients gaining 1.12 life years (LYs) and 1.23 quality-adjusted life years (QALYs) versus SOC. The incremental cost-effectiveness ratio (ICER) for MIDO versus SOC was €68,781 per LY and €62,305 per QALY. Sensitivity analyses showed consistency with base case findings. CONCLUSIONS: MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment.

Treatment patterns and deep molecular response in chronic phase - chronic myeloid leukemia patients treated with second-line nilotinib or dasatinib: a multi-country retrospective chart review study.

Achievement of MR4.5 (BCR-ABL1 ≤ 0.0032% on international scale) is an important goal of tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML). This study describes treatment patterns by region and assesses time to achieve MR4.5 in patients with CML - chronic phase (CP) treated with second-line nilotinib or dasatinib in 10 countries. A multivariate Cox proportional hazards model was used to assess time to MR4.5 for nilotinib versus dasatinib. The model accounted for the competing-risk event of TKI resistance, included random effects for country clustering, and was adjusted for baseline covariates. The study included 280 patients treated with either nilotinib (N = 135 [48%]) or dasatinib (N = 145 [52%]) as second-line TKI with median treatment durations of 19.1 and 18.7 months, respectively. Nilotinib was observed to be better in achieving MR4.5 than dasatinib (adjusted hazard ratio = 1.37, 95% CI [1.11, 1.69]) suggesting second-line nilotinib may perform better in achieving MR4.5 than dasatinib.

Cost-effectiveness analysis for midostaurin versus standard of care in acute myeloid leukemia in the United Kingdom.

AIMS: Midostaurin (MIDO) has been proposed for the treatment of newly-diagnosed adult patients with FMS-like tyrosine kinase 3 mutation-positive (FLT3+) acute myeloid leukemia (AML) in combination with standard chemotherapy. The cost-effectiveness of MIDO and standard of care (SOC) followed by MIDO monotherapy was compared to SOC alone for newly-diagnosed FLT3+ AML in the UK. METHODS: A partitioned survival model was developed from a UK public healthcare system perspective to compare the cost-effectiveness of MIDO plus SOC and SOC over a lifetime horizon. The model included the following health states/partitions: induction, consolidation, monotherapy, complete remission (CR), relapse, stem cell transplantation (SCT), SCT recovery, and post-SCT recovery. Data on CR, overall survival, and adverse events were obtained from a Phase III clinical trial. Overall survival was extrapolated beyond the trial horizon using a 'cure model' approach and data from the Office for National Statistics. Utilities were identified via a systematic review. Routine care utilization was obtained from the National Institute for Health and Care Excellence single technology appraisal for azacitidine in AML (TA399). The costs of drugs and administration, adverse events, hospitalizations, physician visits, and end-of-life care were incorporated. RESULTS: Incremental life years (LYs) and quality-adjusted life years (QALYs) gained by patients on MIDO and SOC versus SOC were 1.67 and 1.47, respectively. At an incremental cost of £54,072 over a lifetime horizon, the ICER was £32,465 per LY and £36,826 per QALY. Sensitivity analyses were generally consistent with the base case findings. CONCLUSIONS: With limited treatments in FLT3+ AML, MIDO represents a clinically significant advance in the management of newly-diagnosed AML. Using a threshold of £50,000 per QALY for end-of-life treatment, MIDO was shown to be a cost-effective option for newly-diagnosed FLT3+ AML.

Systematic review of health state utility values for acute myeloid leukemia.

BACKGROUND: Cost-utility analyses for acute myeloid leukemia (AML) require health state utility values (HSUVs) in order to calculate quality-adjusted life-years (QALYs) for each health state. AIM: This study reviewed AML-related HSUVs that could be used in economic evaluation studies. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were searched from January 2000 to November 2016 for relevant studies that reported quality of life (QoL) and HSUVs in AML. Identified relevant European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 values were mapped to HSUVs. HSUVs for each health state in the AML treatment pathway were then collated. RESULTS: Ten relevant studies were identified. Six were cost-effectiveness analyses utilizing HSUVs for calculation of QALYs, one was an effectiveness analysis (incremental QALY), and two were QoL studies reporting AML-specific utilities. An additional study reported QoL for patients undergoing stem cell transplantation (SCT). Since no study reported HSUVs for relapse, values from a study of secondary AML patients who failed prior treatment for myelodysplastic syndrome were used. Where multiple HSUVs were available, collected values were given priority over assumed values. AML treatment (induction, consolidation, or SCT) was associated with decreased HSUV, while post-treatment complete remission led to increased HSUV. CONCLUSION: There are some methodologically robust HSUVs that can be directly used in economic evaluations for AML. Careful interpretation is advised considering significant differences in methodologies and patient population (inclusion, size). We need to develop HSUVs with larger-sized studies, making greater use of condition-specific data.

The Enhancing Connections Program: a six-state randomized clinical trial of a cancer parenting program.

OBJECTIVE: The purpose of this study was to test the efficacy of a cancer parenting program for child rearing mothers with breast cancer, the Enhancing Connections Program. Primary goals were to decrease maternal depressed mood and anxiety, improve parenting quality, parenting skills and confidence, and enhance the child's behavioral-emotional adjustment to maternal breast cancer. METHOD: A total of 176 mothers diagnosed within 6 months with Stage 0 to Stage III breast cancer and their 8- to 12-year-old child were recruited from medical providers in 6 states: Washington, California, Pennsylvania, Minnesota, Arizona, and Indiana. After consenting and obtaining baseline measures, study participants were randomized into experimental or control groups. Experimental mothers received 5, 1-hr educational counseling sessions at 2-week intervals; controls received a booklet and phone call on communicating and supporting their child about the mother's cancer. Outcomes were assessed at 2 and 12 months. RESULTS: Compared to controls, at 2 months experimental mothers significantly improved on depressed mood and parenting skills; experimental children improved on behavioral-emotional adjustment: total behavior problems, externalizing problems, and anxiety/depressed mood significantly declined. At 1 year, experimental children remained significantly less depressed than controls on both mother- and child-reported measures. The intervention failed to significantly affect parenting self-efficacy or maternal anxiety. CONCLUSIONS: The Enhancing Connections Program benefitted mothers and children in specific areas and warrants refinement and further testing.

Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Hypovitaminosis D is common in obesity and insulin-resistant states. Increased fat mass in patients with non-alcoholic fatty liver disease (NAFLD) may contribute to hypovitaminosis D. To determine the relation among plasma vitamin D concentration, severity of disease and body composition in NAFLD. METHODS: Plasma vitamin D concentration was quantified in 148 consecutive biopsy-proven patients with NAFLD (non-alcoholic steatohepatitis - NASH: n = 81; and hepatic steatosis: n = 67) and healthy controls (n = 39). NAFLD was scored using the NASH CRN criteria. Body composition was quantified by bioelectrical impedance analysis and abdominal CT image analysis. RESULTS: Plasma vitamin D concentration was significantly lower in NAFLD (21.2 ± 10.4 ng/ml) compared with healthy controls (35.7 ± 6.0 ng/ml). Higher NAFLD activity scores were associated with lower plasma concentration of vitamin D (r(2)  = 0.29; P < 0.001). Subgroup analysis among patients with NAFLD showed that patients with NASH had significantly lower (P < 0.01) vitamin D levels than those with steatosis alone (18.1 ± 8.4 vs. 25.0 ± 11.3 ng/ml). Low concentrations of vitamin D were associated with greater severity of steatosis, hepatocyte ballooning and fibrosis (P < 0.05).On multivariate regression analysis, only severity of hepatocyte ballooning was independently associated (P = 0.02) with low vitamin D concentrations. Plasma vitamin D (P = 0.004) and insulin concentrations (P = 0.03) were independent predictors of the NAFLD activity score on biopsy. Patients with NAFLD had higher fat mass that correlated with low vitamin D (r(2)  = 0.26; P = 0.008). CONCLUSIONS: Low plasma vitamin D concentration is an independent predictor of the severity of NAFLD. Further prospective studies demonstrating the impact of vitamin D replacement in NAFLD patients are required.

Characterization of clinical course and usual care patterns in female metastatic breast cancer patients treated with zoledronic acid.

PURPOSE: To describe usual care received by women with bony metastatic breast cancer (ICD-9: 174.xx and 198.5) treated in a United States specialty cancer hospital, an Electronic Medical Record (EMR)-based retrospective review identified 111 deceased female breast cancer patients ≥18 years of age treated with zoledronic acid (ZOL). RESULTS: Baseline symptoms included bone pain/fracture (58.6%), breathing difficulties (24.3%), or mental status changes (11.7%). ZOL was started at/after metastatic diagnosis for 75.7% of women (N = 84), with average administration of 15.9 months (median 11.3). Nearly 20% required reduced ZOL doses, most (54.5%) due to impaired renal function; 61.3% discontinued ZOL due to patient death/disease progression. Adverse events were reported in 10.8%, while 0.9% (N = 1) had a documented osteonecrosis of the jaw. CONCLUSIONS: Initiation of palliative care should be considered early in patients with a history of metastatic breast cancer who report bone pain or other skeletal-related events.

Brief report: Creating a culture of evidence-based practice and nursing research in a pediatric hospital.

Evidence-based practice and nursing research are fundamental to the profession of nursing. However, enculturating these processes into daily nursing practice presents challenges. In an effort to identify these challenges specific to our organization's nursing division, the Barriers to Nursing Research survey was distributed to staff nurses (n=239) to assess barriers in utilizing evidence-based practice and research in their daily practice. Based on these findings, our Evidence-Based Practice/Research Council developed a dissemination plan to be implemented over a 1 year time period that provided staff resources to implement evidence-based practice and nursing research. Upon completion of the year long implementation period, the same Barriers to Nursing Research survey was redistributed to staff (n=157). Pre and post survey results were compared for significance. Outcomes included an increase in projects, nurse driven research, and national presentations and publications.

Perspectives on adherence and persistence with oral medications for cancer treatment.

Ensuring persistence, continuing treatment for the prescribed duration, and adherence-taking medication as prescribed-have been challenges for management of patients with oral cancer and for health care cost containment in real-world settings.

Improving health-care quality through an AFPNP National Nursing Education Collaborative to strengthen PNP curriculum in mental/behavioral health and EBP: lessons learned from academic faculty and clinical preceptors.

In 2004, the Association of Faculty of Pediatric Nurse Practitioners was awarded a grant by the Commonwealth Fund to plan, implement, and evaluate a strengthened national curriculum for students in 20 pediatric nurse practitioner programs throughout the United States. Curricular changes focused on increasing the knowledge and skills of students in the area of evidence-based mental and behavioral health care for children and adolescents. The processes through which this national initiative was undertaken were described in "Strengthening PNP Curricula in Mental/Behavioral Health and Evidence-Based Practice" (B. M. Melnyk et al., 2010). This article focuses on the important perspectives of academic faculty and clinical preceptors and provides critical insight for nursing faculty when planning implementation of significant curricular change. The purpose of this descriptive study was to determine the challenges and facilitators of implementing a strengthened curriculum in didactic and clinical courses to inform nationwide dissemination of this curriculum to all PNP programs throughout the country. Confidential, structured, individual telephone interviews were conducted with academic and clinical preceptors from the schools that had participated in the implementation study. Curricular change presents challenges in most schools of nursing and will be affected by characteristics unique to each institution. Faculty need to be educated regarding the factors that are likely to enhance the process of making important and timely changes in curriculum. Finally, valuable lessons regarding the necessary early engagement of clinical preceptors should inform future curricular change initiatives.

Strengthening PNP curricula in mental/behavioral health and evidence-based practice.

INTRODUCTION: The incidence of mental health/behavioral and developmental problems in children and teens is escalating. However, many primary care providers report inadequate skills to accurately screen, identify, and manage these problems using an evidence-based approach to care. Additionally, educational programs that prepare pediatric nurse practitioners (PNPs) have been slow to incorporate this content into their curriculums. METHODS: The purpose of this project was to implement and evaluate a strengthened curriculum in 20 PNP programs from across the United States that focused on: (a) health promotion strategies for optimal mental/behavioral health and developmental outcomes in children, and (b) screening and evidence-based interventions for these problems. An outcomes evaluation was conducted with faculty and graduating students from the participating programs along with faculty and students from 13 PNP programs who did not participate in the project. RESULTS: Participating schools varied in the speed at which components of the strengthened curriculum were incorporated into their programs. Over the course of the project, faculty from participating programs increased their own knowledge in the targeted areas and reported that their students were better prepared to assess and manage these problems using an evidence-based approach. Although reports of screening for certain problems were higher in the graduating students from the participating schools than the non-participating schools, the overall use of screening tools by students in clinical practice was low. DISCUSSION: There is a need for educational programs to strengthen their curricula and clinical experiences to prepare students to screen for, accurately identify, prevent, and provide early evidence-based interventions for children and teens with mental health/behavioral and developmental problems. This project can serve as a national model for curriculum change.

Polysomnography and self-reported sleep, pain, fatigue, and anxiety in children with active and inactive juvenile rheumatoid arthritis.

OBJECTIVE: To compare polysomnography (PSG) and self-reported sleep, symptoms (pain and fatigue), and anxiety between children with active and inactive juvenile rheumatoid arthritis (JRA) and examine relations among sleep, symptoms, and anxiety. METHODS: Two consecutive nights of PSG, self-reported sleep, and symptoms were obtained in 70 children 6-11 years of age with active (n = 35) or inactive (n = 35) JRA. RESULTS: On the second (study) night, PSG and self-reported sleep variables were not different, but pain and fatigue were significantly higher (both p <.02) in children with active compared to inactive disease. In a stepwise regression, age, medications, disease status, anxiety, evening pain, total sleep time, and arousals explained 36% of the variance in fatigue and age, disease status, and evening pain were significant (all p <.04) predictors of fatigue. All children showed longer sleep latency and reduced sleep efficiency on the first night in the laboratory. CONCLUSIONS: Sleep was not altered in children with active JRA, however, the "first night effect" suggests that valid laboratory sleep assessments require an adaptation night.

Actigraphic sleep and daytime naps in adolescent girls with chronic musculoskeletal pain.

OBJECTIVES: A descriptive pilot study to examine sleep and daytime naps in adolescent girls with chronic musculoskeletal (MSK) pain. METHODS: Seventeen girls (14.9 +/- 2.0 years) completed questionnaires on anxiety and depressive symptoms during their clinic visit, and maintained a sleep diary and wore an actigraph for 7 days. Parents completed a daily diary of their teen's medications and approaches used to ease pain. RESULTS: Average nighttime sleep was 7.2 hr by actigraphy. All participants had mean sleep efficiency <90%. In diaries, 76.5% of the girls reported daytime naps; five girls reported more than three days with naps and more naps were associated with lower sleep efficiency and total nighttime sleep. CONCLUSIONS: Adolescent girls with chronic MSK pain may sleep fewer hours at night than is recommended and nap in the daytime to compensate for insufficient nighttime sleep.

The enhancing connections program: pilot study of a cognitive-behavioral intervention for mothers and children affected by breast cancer.

In 2005, approximately 211,240 women in the US will be diagnosed with early stage breast cancer and an estimated 22% will be child rearing. Research reveals that both mothers and children have elevated distress attributed to the cancer; struggle with how to talk about and deal with the impact of the cancer; and both fear the mother will die. The Enhancing Connections Program (EC) was developed to reduce this cancer-related distress and morbidity. The program involves five, 1-hour educational counseling sessions delivered at 2-week intervals by specially trained clinicians. This study reports on the program's short-term impact on mothers' and children's adjustment. Thirteen households were recruited within 7.5 months of the mother's diagnosis with early stage breast cancer. Impact was evaluated within a single group design using data obtained from standardized questionnaires with established reliability and validity. Results revealed significant improvements in the mother's depressed mood, anxiety, and self-confidence to assist her child (mother report). There were also significant decreases in the child's behavioral problems (mother and father report); the child's cancer-related worries (child report); and the child's anxiety/depressed mood (mother and father report). Further evaluation is warranted within a clinical trial.

Dysfunctional elimination syndrome is a negative predictor for vesicoureteral reflux.

PURPOSE: We investigated the likelihood of finding vesicoureteral reflux (VUR) in patients with urinary tract infections (UTIs), accompanied by fever or dysfunctional elimination syndrome (DES). MATERIALS AND METHODS: Two hundred consecutive voiding cystourethrograms performed in 1997-2002 for a diagnosis of UTI were reviewed. Fever, DES, and the grade and laterality of VUR were recorded. Patients were stratified into two groups by age to allow for assessment of DES symptoms in the older patient population: <2 years (n=68) and > or =2 years (n=132). Ratios were compared using a two-tailed Fisher's exact test. RESULTS: Of the children> or =2 years old, 64/132 (48%) had VUR. Patients who were non-febrile with DES were less likely than patients who were febrile without DES to have VUR [12/34 (35%) vs 23/34 (68%), P=0.02], whereas the risk of dilating VUR [5/34 (15%) vs 11/34 (32%), P=0.15] and bilateral VUR [4/34 (12%) vs 11/34 (32%), P=0.08] was not statistically different. In febrile patients, the presence of DES was associated with a lower risk of VUR [22/51 (43%) vs 23/34 (68%), P=0.03] and dilating VUR [5/51 (10%) vs 11/34 (32%), P=0.01], but not bilateral VUR [8/51 (16%) vs 11/34 (32%), P=0.11]. CONCLUSIONS: Children with non-febrile UTI and DES have a significantly lower risk of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES is a negative predictor for VUR.

Assessing the strength and integrity of an intervention.

PURPOSE/OBJECTIVES: To evaluate the strength and integrity of a pilot behavioral intervention designed to assist mothers with breast cancer and their children. RESEARCH APPROACH: A single-group analysis of the strength and integrity characteristics of an intervention developed for a pilot research study. SETTING: Homes of study participants in an urban area. PARTICIPANTS: Seven households with a mother and father and one household with a single mother. METHODOLOGIC APPROACH: Observer-reported checklists, audiorecorded intervention session data, and structured interview data obtained from study participants. MAIN RESEARCH VARIABLES: Strength of the intervention included dimensions such as the theoretical foundation, competence of the interventionist, and specificity to the breast cancer experience in the family. Intervention integrity consisted of adherence by the interventionist and participants to the intervention plan. FINDINGS: The strength of the intervention was determined to be an asset. Careful planning had included a framework, a defined set of scripted sessions, a competent interventionist, and content specific to the breast cancer experience. In regard to integrity, the protocol content was delivered as scripted. Improvements in the dosage and purity dimensions were found to be needed. Homework assignments and in-session skill-building approaches with the mothers were refined. CONCLUSIONS: An intervention can be examined carefully for strength and integrity with established criteria to determine improvements needed. INTERPRETATION: A clinical research protocol can be improved through an assessment of an intervention's strength and integrity.

The use of a positive procedure to increase engagement on-task and decrease challenging behavior.

The exhibition of stereotypic and self-injurious behavior (SIB) combined with a lack of work engagement makes it very difficult to place a person with severe disabilities in an integrated work environment. The purpose of this research was to examine use of a positive procedure to increase engagement on-task and reduce self-injurious slapping and stereotypic clothes manipulation by a 46-year-old man with severe disabilities. A single-subject research design was used to examine the effects of the combined DRA-DRO (differential reinforcement of alternative behavior-differential reinforcement of other behavior) procedure in fostering more appropriate behavior. Following 30 years of institutionalization, the man was successfully integrated into community-based employment.

Making the most of the moment: when a child's mother has breast cancer.

The demands and uncertainties associated with adjustments to chronic illness present challenges to maintaining a stable family life. Little has been reported about mother-child relationships within the cancer experience and even less about interventions that may be useful to help these dyads maintain stability. The focus of this article is a pilot study of an intervention addressing the mother-child relationship of women with breast cancer and their school-aged children. A part of the data collection comprised interviews of mothers and fathers to assess their perceptions of the influence of the intervention on the quality of the mother-child relationships after the program. Using inductive content analysis, the fathers' and mothers' data were organized into categories, domains, and an explanatory construct, called making the most of the moment. The processes by which the intervention affected the mother-child relationships and implications for professionals who work with families are reported.