Comparative evaluation of the health utilities index mark 3 and the short form 6D: evidence from an individual participant data meta-analysis of very preterm and very low birthweight adults.

BACKGROUND: The most appropriate preference-based health-related quality of life (HRQoL) instruments for trials or research studies that ascertain the consequences of individuals born very preterm and/or low birthweight (VP/VLBW) are not known. Agreement between the HUI3 and SF-6D multi-attribute utility measures have not been previously investigated for VP/VLBW and normal birthweight or term-born controls. This study examined the agreement between the outputs of the HUI3 and SF-6D measures among adults born VP/VLBW and normal birthweight or term born controls. METHODS: We used two prospective cohorts of individuals born VP/VLBW and controls contributing to the 'Research on European Children and Adults Born Preterm' (RECAP) consortium which assessed HRQoL using two preference-based measures. The combined dataset of individual participant data (IPD) included 407 adult VP/VLBW survivors and 367 controls, ranging in age from 18 to 26 years. Bland-Altman plots, intra-class correlation coefficients, and generalized linear mixed models in a one-step approach were used to examine agreement between the measures. RESULTS: There was significant discordance between the HUI3 and SF-6D multi-attribute utility measures in the VP/VLBW sample, controls, and in the combined samples. Agreement between the HUI3 and SF-6D multi-attribute utility measures was weaker in controls compared with VP/VLBW individuals. CONCLUSIONS AND RELEVANCE: The HUI3 and SF-6D each provide unique information on different aspects of health status across the groups. The HUI3 better captures preterm-related changes to HRQoL in adulthood compared to SF-6D. Studies focused on measuring physical or cognitive aspects of health will likely benefit from using the HUI3 instead of the SF-6D, regardless of gestational age at birth and birthweight status.

Economic impact of genomic diagnostics for intermediate-risk acute myeloid leukaemia.

Acute Myeloid Leukaemia (AML) is a rare but serious group of diseases that require critical decision-making for curative treatment. Over the past decade, scientific discovery has revealed dozens of prognostic gene mutations for AML while sequencing costs have plummeted. In this study, we compared the cost-effectiveness of multigene integrative analysis (genomic analysis) with the standard molecular testing currently used for diagnosis of intermediate-risk AML. We used a decision analytic model with data for costs and outcomes from British Columbia, Canada, to assess the long-term (10-year) economic impacts. Our results suggest that genomic analysis would result in a 26% increase in the use of first-remission allogeneic stem cell transplantation. The resulting treatment decisions and downstream effects would come at an additional cost of $12 556 [2013 Canadian dollars (CAD)] per person and the incremental cost-effectiveness ratio would be $49 493 per quality-adjusted life-year gained. Cost-effectiveness was dependent on quality of life during the long-term (5-10) years of survival, relapse rates following first-remission chemotherapy and the upfront cost of transplantation. Non-relapse mortality rates, short-term quality of life and the cost of genomic sequencing had only minor impacts. Further research on post-remission outcomes can lead to improvements in the cost-effectiveness of curative treatments for AML.

Perinatal Regionalization and Implications for Long-Term Health Outcomes in Cerebral Palsy.

BACKGROUND: Perinatal regionalization is linked to improved neonatal outcomes; however, the effects on long-term outcomes in cerebral palsy (CP) are not known. We estimate the effect of highest levels of neonatal care available at delivery on the risk of developing a nonambulatory CP status. METHODS: Children with CP born in Quebec from the Canadian CP Registry excluding postneonatal causes were included (N=360). We estimate the effect of level of care available at delivery on risk of nonambulatory status among children with CP using propensity score matching and instrumental variables methods to adjust for differences in case mix among the three groups of hospitals. The outcome variable is an indicator for CP nonambulation assigned according to Gross Motor Function Classification System (levels IV and V). This study used data that predated therapeutic hypothermia in Quebec. RESULTS: Propensity score estimates of change in the adjusted risk of having a nonambulatory CP status because of birth at level II versus level I is -0.081, 95% confidence interval (CI; -0.2182 to 0.0562); level III versus level I is -0.072 95% CI (-0.225 to 0.08), and level III versus level II is 0.157 95% CI (0.027 to 0.286). CONCLUSIONS: Differences in levels of neonatal care available at hospital where the delivery was carried out are not associated with the risk of a nonambulatory CP phenotype. This suggests that level of care and associated medical technology within the Quebec regionalized neonatal-perinatal system is used efficiently because it does not offer any further marginal benefit in the reduction of severe CP outcomes. The system works well as it is, which is supportive of the perinatal regionalization. The success of the neonatal resuscitation program and referral of high-risk births to regional hospitals with sufficient obstetric and perinatal competence and resources may contribute to this lack of variability.

Are there patients with an intracapsular fracture of the hip who may benefit from an uncemented hemiarthroplasty?

Aims: Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty - the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most. Methods: We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively. Results: Our analysis revealed a complex landscape of responses to the use of a cemented hemiarthroplasty in the 12 months after surgery. There was heterogeneity of effects with regard to baseline characteristics, including age, pre-injury health status, and lifestyle factors such as alcohol consumption. This heterogeneity was greater at the one-month mark than at subsequent follow-up timepoints, with particular regard to subgroups based on age. However, for all subgroups, the effect estimates for quality of life lay within the confidence intervals derived from the analysis of all patients. Conclusion: The use of a cemented hemiarthroplasty is expected to increase health-related quality of life compared with modern uncemented hemiarthroplasty for all subgroups of patients aged > 60 years with a displaced intracapsular fracture of the hip.

COVID-19 Induced Environments, Health-Related Quality of Life Outcomes and Problematic Behaviors: Evidence from Children with Syndromic Autism Spectrum Disorders.

Between July 2020 and January 2021, 230 principal caregivers completed a questionnaire to measure proxy-assessed health-related quality of life outcomes (HRQoL), behavioral outcomes in children with syndromic autism spectrum disorders and COVID-19 induced changes to lifestyle and environments. HRQoL and behavioral outcomes reported earlier during the pandemic were generally worse compared to those reported later. COVID-19 induced reduction to a caregiver's mental health appointments, and hours spent watching TV were associated with decreases in HRQoL and increased the likelihood of problematic behaviors. Increasing time outdoors and time away from digital devices were positively associated with HRQoL and behaviors and might protect children from COVID-19 induced restrictions.

Psychometric Performance of Generic Childhood Multi-Attribute Utility Instruments in Preterm and Low Birthweight Populations: A Systematic Review.

BACKGROUND: Individuals born preterm (gestational age < 37 weeks) and/or at low birthweight (<2500 g) are at increased risk of health impairments from birth to adulthood. This review aimed to evaluate the psychometric performance of generic childhood-specific or childhood-compatible multi-attribute utility instruments (MAUIs) in preterm and/or low birthweight (PLB) populations. METHODS: Searches covered seven databases, including studies that targeted childhood (aged < 18 years) and/or adult (≥18 years) PLB populations; provided psychometric evidence for generic childhood-specific or compatible MAUI(s) (any language version); and published in English. Eighteen psychometric properties were evaluated using a four-part criteria rating system. Data syntheses identified psychometric evidence gaps and summarised the psychometric assessment methods/results. RESULTS: A total of 42 studies were included, generating 178 criteria rating outputs across four MAUIs: 17D, CHSCS-PS, HUI2, and HUI3. Moreover, 64.0% of outputs concerned the HUI3 MAUI, and 38.2% related to known-group validity. There was no evidence for five psychometric properties. Only 6.7% of outputs concerned reliability and proxy-child agreement. No MAUI outperformed others across all properties. The frequently applied HUI2 and HUI3 lacked content validity evidence. CONCLUSIONS: This psychometric evidence catalogue should inform the selection of MAUI(s) suited to the specific aims of applications targeting PLB populations. Further psychometric research is warranted to address the gaps in psychometric evidence.

Health-Related Quality-of-Life Outcomes of Very Preterm or Very Low Birth Weight Adults: Evidence From an Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVE: Assessment of health-related quality of life for individuals born very preterm and/or low birthweight (VP/VLBW) offers valuable complementary information alongside biomedical assessments. However, the impact of VP/VLBW status on health-related quality of life in adulthood is inconclusive. The objective of this study was to examine associations between VP/VLBW status and preference-based health-related quality-of-life outcomes in early adulthood. METHODS: Individual participant data were obtained from five prospective cohorts of individuals born VP/VLBW and controls contributing to the 'Research on European Children and Adults Born Preterm' Consortium. The combined dataset included over 2100 adult VP/VLBW survivors with an age range of 18-29 years. The main exposure was defined as birth before 32 weeks' gestation (VP) and/or birth weight below 1500 g (VLBW). Outcome measures included multi-attribute utility scores generated by the Health Utilities Index Mark 3 and the Short Form 6D. Data were analysed using generalised linear mixed models in a one-step approach using fixed-effects and random-effects models. RESULTS: VP/VLBW status was associated with a significant difference in the Health Utilities Index Mark 3 multi-attribute utility score of - 0.06 (95% confidence interval - 0.08, - 0.04) in comparison to birth at term or at normal birthweight; this was not replicated for the Short Form 6D. Impacted functional domains included vision, ambulation, dexterity and cognition. VP/VLBW status was not associated with poorer emotional or social functioning, or increased pain. CONCLUSIONS: VP/VLBW status is associated with lower overall health-related quality of life in early adulthood, particularly in terms of physical and cognitive functioning. Further studies that estimate the effects of VP/VLBW status on health-related quality-of-life outcomes in mid and late adulthood are needed.

Resilience, and positive parenting in parents of children with syndromic autism and intellectual disability. Evidence from the impact of the COVID-19 pandemic on family's quality of life and parent-child relationships.

Family quality of life (FQoL) outcomes collected during the first year of COVID-19 has been combined with 2018 data to estimate the outbreak's impact on parental outcomes on a sample of 230 families with syndromic autistic children and those with intellectual disabilities (IDs). Despite challenges imposed by the COVID-19 outbreak, our study found that FQoL outcomes reported by participating parents during the first year of COVID-19 appears to be similar to ratings from a prepandemic study of families with the same conditions. Parents of children in our sample generally displayed a stable functioning trajectory as measured by the validated FQoL instrument. Across syndromic autistic groups considered, families reported that their relationships with their children were positive. Our findings provide evidence of families' resilience which might explain the presence of positive parent-child interactions during COVID-19. Exploring mechanisms which would explain how families with autistic and ID children confront, manage disruptive experiences, and buffer COVID-19 induced stress is a fruitful direction for future research.

Health-Related Quality of Life in Pediatric Patients with Syndromic Autism and their Caregivers.

Children with autism have a significantly lower quality of life compared with their neurotypical peers. While multiple studies have quantified the impact of autism on health-related quality of life (HRQoL) through standardized surveys such as the PedsQL, none have specifically investigated the impact of syndromic autism. Here we evaluate HRQoL in children diagnosed with three genetic disorders that strongly predispose to syndromic autism: Phelan-McDermid syndrome (PMD), Rett syndrome (RTT), and SYNGAP1-related intellectual disability (SYNGAP1-ID). We find the most severely impacted dimension is physical functioning. Strikingly, syndromic autism results in worse quality of life than other chronic disorders including idiopathic autism. This study demonstrates the utility of caregiver surveys in prioritizing phenotypes, which may be targeted as clinical endpoints for genetically defined ASDs.

The effectiveness of generic emails versus a remote knowledge broker to integrate mood management into a smoking cessation programme in team-based primary care: a cluster randomised trial.

BACKGROUND: Knowledge brokering is a knowledge translation approach that has been gaining popularity in Canada although the effectiveness is unknown. This study evaluated the effectiveness of generalised, exclusively email-based prompts versus a personalised remote knowledge broker for delivering evidence-based mood management interventions within an existing smoking cessation programme in primary care settings. METHODS: The study design is a cluster randomised controlled trial of 123 Ontario Family Health Teams participating in the Smoking Treatment for Ontario Patients programme. They were randomly allocated 1:1 for healthcare providers to receive either: a remote knowledge broker offering tailored support via phone and email (group A), or a generalised monthly email focused on tobacco and depression treatment (group B), to encourage the implementation of an evidence-based mood management intervention to smokers presenting depressive symptoms. The primary outcome was participants' acceptance of a self-help mood management resource. The secondary outcome was smoking abstinence at 6-month follow-up, measured by self-report of smoking abstinence for at least 7 previous days. The tertiary outcome was the costs of delivering each intervention arm, which, together with the effectiveness outcomes, were used to undertake a cost minimisation analysis. RESULTS: Between February 2018 and January 2019, 7175 smokers were screened for depression and 2765 (39%) reported current/past depression. Among those who reported current/past depression, 29% (437/1486) and 27% (345/1277) of patients accepted the mood management resource in group A and group B, respectively. The adjusted generalised estimating equations showed that there was no significant difference between the two treatment groups in patients' odds of accepting the mood management resource or in the patients' odds of smoking abstinence at follow-up. The cost minimisation analysis showed that the email strategy was the least costly option. CONCLUSIONS: Most participants did not accept the resource regardless of remote knowledge broker strategy. In contexts with an existing KT infrastructure, decision-makers should consider an email strategy when making changes to a programme given its lower cost compared with other strategies. More research is required to improve remote knowledge broker strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03130998 . Registered April 18, 2017, (Archived on WebCite at www.webcitation.org/6ylyS6RTe ).

The impact of high intensity care around birth on long-term neurodevelopmental outcomes.

BACKGROUND: An equitable and affordable healthcare system requires a constant search for the optimal way to deliver increasingly expensive neonatal care. Therefore, evaluating the impact of hospital intensity around birth on long-term health outcomes is necessary if we are to assess the value of high intensity neonatal care against its costs. METHODS: This study exploits uneven geographical distribution of high intensity birth hospitals across Canada to generate comparisons across similar Cerebral Palsy (CP) related births treated at hospitals with different intensities. We employ a rich dataset from the Canadian Multi-Regional CP Registry (CCPR) and instrumental variables related to the mother's location of residence around birth. RESULTS: We find that differences in hospitals' intensities are not associated with differences in clinically relevant, long-term CP health outcomes. CONCLUSIONS: Our results suggest that existing matching mechanism of births to hospitals within large metropolitan areas could be improved by early detection of high risk births and subsequent referral of these births to high intensity birthing centers. Substantial hospitalization costs might be averted to Canadian healthcare system ($16 million with a 95% CI of $6,131,184 - $24,103,478) if CP related births were assigned to low intensity hospitals and subsequently transferred if necessary to high intensity hospitals.

Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy.

Targeted whole-exome sequencing (WES) is a powerful diagnostic tool for a broad spectrum of heterogeneous neurological disorders. Here, we aim to examine the impact on diagnosis, treatment and cost with early use of targeted WES in early-onset epilepsy. WES was performed on 180 patients with early-onset epilepsy (≤5 years) of unknown cause. Patients were classified as Retrospective (epilepsy diagnosis >6 months) or Prospective (epilepsy diagnosis <6 months). WES was performed on an Ion Proton™ and variant reporting was restricted to the sequences of 620 known epilepsy genes. Diagnostic yield and time to diagnosis were calculated. An analysis of cost and impact on treatment was also performed. A molecular diagnoses (pathogenic/likely pathogenic variants) was achieved in 59/180 patients (33%). Clinical management changed following WES findings in 23 of 59 diagnosed patients (39%) or 13% of all patients. A possible diagnosis was identified in 21 additional patients (12%) for whom supporting evidence is pending. Time from epilepsy onset to a genetic diagnosis was faster when WES was performed early in the diagnostic process (mean: 145 days Prospective vs. 2,882 days Retrospective). Costs of prior negative tests averaged $8,344 per patient in the Retrospective group, suggesting savings of $5,110 per patient using WES. These results highlight the diagnostic yield, clinical utility and potential cost-effectiveness of using targeted WES early in the diagnostic workup of patients with unexplained early-onset epilepsy. The costs and clinical benefits are likely to continue to improve. Advances in precision medicine and further studies regarding impact on long-term clinical outcome will be important.

Participation in the special supplemental nutrition program for women, infants, and children is not associated with early childhood socioemotional development: Results from a longitudinal cohort study.

Socioemotional development in early childhood has long-term impacts on health status and social outcomes, and racial and socioeconomic disparities in socioemotional skills emerge early in life. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is an early childhood nutrition intervention with the potential to ameliorate these disparities. Our objective was to assess the impact of WIC on early socioemotional development in a longitudinal study. We examined the association between WIC participation and scores on the Brief Infant Toddler Social Emotional Assessment (BITSEA) in 327 predominantly African American mother-child dyads who were participants in the longitudinal Conditions Affecting Neurocognitive Development in Early Life (CANDLE) Study (Memphis, TN). To account for selection bias, we used within-child fixed effects to model the variability in each child's BITSEA scores over two measurement occasions (ages 12 and 24 months). Final models were adjusted for time-varying characteristics including child age, maternal stress, mental health, child abuse potential, marital status, and food stamp participation. In fully adjusted models, we found no statistically significant effect of WIC on change in socioemotional development (ß = 0.22 [SD = 0.39] and ß = - 0.58 [SD = 0.79] for BITSEA Competence and Problem subdomains, respectively). Using rigorous methods and a longitudinal study design, we found no significant association between WIC and socioemotional development in a high needs population. This finding suggests that early childhood interventions that more specifically target socioemotional development are necessary if we are to reduce racial disparities in socioemotional skills and prevent poor social and health outcomes across the life course.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

BACKGROUND: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. METHODS: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. RESULTS: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061). CONCLUSION: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

Cost-effectiveness of rituximab in follicular lymphoma.

In advanced follicular lymphoma, rituximab is currently used with chemotherapy as induction therapy, and as maintenance monotherapy following induction in previously untreated patients and treatment-experienced relapsed/refractory patients. Herein, the authors characterize the clinical effectiveness, safety and cost-effectiveness of rituximab in follicular lymphoma, based on the literature review. Rituximab has a favorable safety profile and has been shown to improve progression-free survival, with some evidence of improvements to overall survival, particularly for relapsed/refractory patients. Rituximab has consistently been found to have a favorable economic profile, with cost per quality-adjusted life year falling within standard thresholds for cost-effectiveness. Challenges in cost-effectiveness analysis include the fact that life expectancy for patients with follicular lymphoma exceeds the period of available follow-up data and that treatment pathways are more complex than the model structures frequently used in oncology models. As data accrue and more complex models are developed, the cost-effectiveness of rituximab can be more accurately assessed.