Newborn screening for neurodevelopmental diseases: Are we there yet?

In the US, newborn screening (NBS) is a unique health program that supports health equity and screens virtually every baby after birth, and has brought timely treatments to babies since the 1960's. With the decreasing cost of sequencing and the improving methods to interpret genetic data, there is an opportunity to add DNA sequencing as a screening method to facilitate the identification of babies with treatable conditions that cannot be identified in any other scalable way, including highly penetrant genetic neurodevelopmental disorders (NDD). However, the lack of effective dietary or drug-based treatments has made it nearly impossible to consider NDDs in the current NBS framework, yet it is anticipated that any treatment will be maximally effective if started early. Hence there is a critical need for large scale pilot studies to assess if and how NDDs can be effectively screened at birth, if parents desire that information, and what impact early diagnosis may have. Here we attempt to provide an overview of the recent advances in NDD treatments, explore the possible framework of setting up a pilot study to genetically screen for NDDs, highlight key technical, practical, and ethical considerations and challenges, and examine the policy and health system implications.

Adherence to imatinib among patients attending Saskatchewan Cancer Agency Pharmacies.

RATIONALE: Chronic use of imatinib confers an important survival benefit for individuals with chronic myeloid leukemia. In Saskatchewan, the provincial cancer agency addresses important barriers to adherence by providing imatinib at no cost through specialized cancer centers. OBJECTIVE: To describe adherence to imatinib dispensed through the Saskatchewan Cancer Agency. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of electronic pharmacy dispensation records from the Saskatchewan Cancer Agency. All dispensations for imatinib classified for hematologic malignancies were electronically abstracted by cancer center personnel and securely forwarded to investigators with all meaningful patient identifiers removed. All subjects receiving a new dispensation (i.e. using a 6-month washout period) for imatinib between 1 June 2004 and 31 December 2011 were included. The primary endpoint was optimal adherence to imatinib during the first year of therapy, defined as a medication possession ratio ≥ 80%. RESULTS: Ninety-one subjects were started on imatinib during the observation period. During the first year of therapy, 82.4% (75/91) maintained a medication possession ratio ≥ 80%. The percentage of individuals maintaining optimal adherence decreased only slightly when the observation period was extended to 2 (78.4%) or 3 years (78.8%). CONCLUSIONS: Non-adherence to imatinib is relatively infrequent when provided by the Saskatchewan Cancer Agency.

Reimbursement for supportive cancer medications through private insurance in Saskatchewan.

BACKGROUND: As demand for cancer treatment grows, and newer, more expensive drugs become available, public payers in Canada are finding it increasingly difficult to fund the full range of available cancer drugs. OBJECTIVE: To determine the extent of private drug coverage for supportive cancer treatments in Saskatchewan, preparatory to exploring the potential for cost-sharing. METHODS: Patients who presented for chemotherapy and who provided informed consent for participation were surveyed regarding their access to private insurance. Insurers were contacted to verify patients' level of coverage for supportive cancer medications. Groups with specified types of insurance were compared statistically in terms of age, income bracket, time required to assess insurance status, and amount of deductible. Logistic regression was used to determine the effect of patients' age and income on the probability of having insurance. RESULTS: Of 169 patients approached to participate, 156 provided consent and completed the survey. Their mean age was 58.5 years. About two-fifths of all patients (64 or 41%) were in the lowest income bracket (up to $30 000). Sixty-three (40%) of the patients had private insurance for drugs, and 36 (57%) of these plans included reimbursement for supportive cancer medications. A deductible was in effect in 31 (49%) of the plans, a copayment in 28 (44%), and a maximum payment in 8 (13%). Income over $50 000 was a significant predictor of access to drug insurance (p = 0.003), but age was not significantly related to insurance status. CONCLUSIONS: A substantial proportion of cancer patients in this study had access to private insurance for supportive cancer drugs for which reimbursement is currently provided by the Saskatchewan Cancer Agency. Cost-sharing and optimal utilization of the multipayer environment might offer a greater opportunity for public payers to cover future innovative and supportive therapies for cancer, but further study is required to determine whether a cost-sharing program would be cost-effective and in the best interest of patients.

Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study.

OBJECTIVES: The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer. METHODS: Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables. RESULTS: One hundred nineteen eligible patients with median age of 61 years and male/female ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5-7.5] versus 4.0 months (95% CI, 2.9-5.1) with GnP (P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7-11) compared with 9.0 months (95% CI, 4.2-13.8) with GnP (P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41-0.97], male sex (HR, 0.65; 95% CI, 0.43-0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28-0.86) were correlated with survival. CONCLUSIONS: Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile.

Patient-centered evaluation of outcomes from rehabilitation for chronic disabling spinal disorders: the impact of personal goal achievement on patient satisfaction.

BACKGROUND CONTEXT: The multiplicity of biopsychosocial and economic facets of chronic disabling back and/or neck pain complicates the treatment outcomes measurement. Our previous work showed that personal functional goal achievement contributed more toward patient satisfaction with the outcome than did traditional self-reports of pain and physical function or measured strength, flexibility, and endurance among functional restoration program (FRP) graduates with chronic disabling back and/or neck pain. PURPOSE: The primary goal was to compare the impact on patient satisfaction of pain and functional goal achievement versus self-reports of pain and physical function. STUDY DESIGN: This was an observational study of all patients with chronic disabling back and/or neck pain completing an FRP between June 2008 and May 2009. OUTCOME MEASURES: Before the treatment, participants recorded personal 3-month goals for pain, work, recreation, and activities of daily living. At least 3 months later, all graduates were sent a follow-up survey displaying the patient's pretreatment functional goals and eliciting the patient's assessment of functional goal achievement; current pain magnitude, "satisfaction with the overall results for your pain problem;" and responses to the Short Form-36v2 Physical Functioning subscale (PF-10). METHODS: Pain goal achievement was calculated as the difference between the pretreatment pain goal and follow-up pain magnitude. Linear regression was used to evaluate the association between satisfaction and four variables (follow-up pain; PF-10; pain goal achievement; functional goal achievement), individually and then together in a full model. RESULTS: Of the 82 patients surveyed, 62 responded completely. Mean age was 44 years, with 48% female and 35% on worker's compensation. The model R(2) combining all four variables explained 0.6033 of the variance in satisfaction. Each variable by itself was significantly related to patient satisfaction at p<.001, but the overlap in association was large. The unique contributions (R(2)) to the variation in satisfaction were the following: functional goal achievement: 0.0471; PF-10 score: 0.0229; pain magnitude: 0.0178; and pain goal achievement: 0.0020. CONCLUSIONS: At least 3 months after the treatment, functional goal achievement had by far the greatest impact on patient satisfaction, followed by PF-10 score, pain magnitude, and, finally, pain goal achievement. Functional goal achievement has great potential as a tool for patient-centered treatment decision-making and outcomes measurement for people with chronic disabling back and/or neck pain and their health care providers.

The impact of personal functional goal achievement on patient satisfaction with progress one year following completion of a functional restoration program for chronic disabling spinal disorders.

STUDY DESIGN: This prospective cohort study investigated personal goal achievement and satisfaction with progress in patients with chronic disabling spinal disorders (CDSD). OBJECTIVE: This study examined the relationships between satisfaction with progress and several alternative outcome measures for CDSD patients at least 1 year after completing a functional restoration program (FRP). SUMMARY OF BACKGROUND DATA: Treatment outcome measures for CDSD commonly include pain, physical capacities, and functional/vocational status. These factors are weakly correlated and may not reflect individual patients' perspectives and priorities. METHODS: On enrollment in the FRP, patients' pretreatment functional, work, and recreation goals were recorded. Pre- and end-of-program clinical measures included: pain, disability, fear avoidance, lifting, trunk flexibility, and treadmill endurance. At least 1 year after program completion surveys were mailed to consecutive FRP graduates. Nonresponders were surveyed by telephone when possible. Surveys included each patient's personal pretreatment goals, and assessed Average Pain, SF-36 Physical Function, and satisfaction "with the progress made with your pain problem." Each patient indicated levels of importance and achievement for each personal goal, and these scores were integrated to yield a goal achievement score (GAS). Linear regression was used to test the relationships between 1-year satisfaction with progress and the following variables: baseline to end-of-program change in clinical measures, and 1-year pain, physical function, and GAS. RESULTS: Of the 106 surveys mailed, 89 (84%) were returned and 86 (81%) had complete data for analysis. None of the pre-post-program clinical measures was significantly correlated with satisfaction (overall R2 = 0.013, P < 0.74). In contrast, year-end Average Pain (R2= 0.28), Physical Function (R2 = 0.29), and GAS (R2 = 0.29) were each significantly correlated (P < 0.0001) with satisfaction, with a combined R2 = 0.43, P < 0.0001. Of these variables, GAS had the highest unique contribution to satisfaction. CONCLUSION: For CDSD patients 1 year after completing rehabilitation, compared to more traditional outcomes, GAS provided the greatest unique contribution to patient satisfaction. Goal achievement may be a valuable patient-centered measure of treatment outcome.