Real-world outcomes of mepolizumab for the treatment of severe eosinophilic asthma in Canada: an observational study.

BACKGROUND: Mepolizumab, the first widely available anti-interleukin 5 biologic, targets eosinophilic inflammation and has been shown in clinical trials to reduce exacerbations, oral corticosteroid dependence, and healthcare utilization in patients with severe asthma. The impact of mepolizumab in a real-world, publicly funded healthcare setting is unknown. The objective of this study was to describe the demographics and clinical characteristics of real-world patients receiving mepolizumab, and to compare asthma-related outcomes and associated asthma-related costs before and during mepolizumab use. METHODS: This retrospective, observational study in Ontario, Canada, included patients initiating mepolizumab between February 2016 and March 2019. Patients were identified using the mepolizumab patient support program and linked to the Institute for Clinical Evaluative Sciences database of publicly accessed healthcare. Patient outcomes were obtained for 12 months pre- and post-mepolizumab initiation and compared. RESULTS: A total of 275 patients were enrolled in the overall patient support program cohort (mean [standard deviation] age 57.6 [13.5] years, mean [standard deviation] of the median per-patient eosinophil count 540.4 [491.9] cells/µL). Mepolizumab was associated with reductions in asthma exacerbations (46.1%, P < 0.001) and in the number of asthma-related visits to general practitioners (40.2%, P < 0.001), specialists (27.2%, P < 0.001), and emergency departments (52.1%, P < 0.001). Associated costs were significantly lower post- versus pre-mepolizumab for asthma-related general practitioner and specialist visits, and for all-cause emergency department visits and hospital admissions. CONCLUSIONS: In a real-world population of Canadian patients with severe asthma with an eosinophilic phenotype, the use of mepolizumab within a patient support program reduced asthma exacerbations and decreased asthma-related healthcare resource utilization and associated costs.

Community-based screening and triage connecting First Nations children and youth to local supports: a cross-sectional study.

BACKGROUND: First Nations children in Canada experience health inequities. We aimed to determine whether a self-report health app identified children's needs for support earlier in their illness than would typically occur. METHODS: Children (aged 8 to 18 yr) were recruited from a rural First Nation community. Children completed the Aaniish Naa Gegii: the Children's Health and Well-being Measure (ACHWM) and then met with a local mental health worker who determined their risk status. ACHWM Emotional Quadrant Scores (EQS) were compared between 3 groups of children: healthy peers (HP) who were not at risk, those with newly identified needs (NIN) who were at risk and not previously identified, and a typical treatment (TT) group who were at risk and already receiving support. RESULTS: We included 227 children (57.1% girls), and the mean age was 12.9 (standard deviation [SD] 2.9) years. The 134 children in the HP group had a mean EQS of 80.1 (SD 11.25), the 35 children in the NIN group had a mean EQS of 67.2 (SD 13.27) and the 58 children in the TT group had a mean EQS of 66.2 (SD 16.30). The HP group had significantly better EQS than the NIN and TT groups (p < 0.001). The EQS did not differ between the NIN and TT groups (p = 0.8). INTERPRETATION: The ACHWM screening process identified needs for support among 35 children, and the associated triage process connected them to local services; the similarity of EQS in the NIN and TT groups highlights the value of community screening to optimize access to services. Future research will examine the impact of this process over the subsequent year in these groups.

A targeted literature review of the burden of illness for spine-related neuropathic pain in Japan.

BACKGROUND: Neuropathic pain (NeP) is pain provoked by damage or disease in the nervous system and about one in three Japanese patients with spinal disorders are highly likely to have NeP. The humanistic and economic burden of illness (BOI) of spine-related NeP represents unmet medical needs that should be addressed. The purpose of this targeted literature review was to synthesize the available evidence on the BOI of spine-related NeP in Japanese patients. METHODS: PubMed and ICHUSHI were searched for relevant studies published between January 2010 and December 2020, in English or Japanese. The population included patients with one or more of prespecified spinal disorders and NeP, and outcomes of interest were data related to humanistic or economic burden. RESULTS: Out of 32 studies that assessed the BOI of spine-related disorders in Japan, only six specifically assessed spine-related NeP. Among these studies, five different validated questionnaires were used to measure humanistic burden. Spine-related NeP was consistently shown to be related with a poorer health-related quality of life and higher levels of anxiety and depression compared to the general population as well as patients with nociceptive pain. No articles directly evaluating economic burden were identified in this search, so an exploratory analysis was conducted. Reduction in work productivity by people experiencing spine-related NeP in the whole of Japan were estimated to total JPY 172,266,780,480 per year. CONCLUSIONS: The humanistic burden of spine-related NeP on Japanese patients is considerable, not only physically but also mentally. Exploratory analysis of the economic burden illustrates the possibility of substantial societal costs associated with NeP. In order to better understand the depth of BOI and the unmet medical need caused by spine-related NeP, further studies on real-world outcomes are recommended.

Rasch Measurement Theory's contribution to the psychometric properties of a co-created measure of health and wellness for Indigenous children and youth.

OBJECTIVES: To determine how Rasch Measurement Theory (RMT) methods can be used to assess the psychometric properties of the Aaniish Naa Gegii: the Children's Health and Wellbeing Measure (ACHWM) and Qanuippit. STUDY DESIGN AND SETTING: Indigenous children aged 8-18 years, from five communities, completed the 62-item ACHWM. We applied RMT methods to ACHWM data from 401 children (mean age 13.4 ± 3.4 years; 51% male) from across Ontario to examine how well the items captured the full range (±3 logit) of the concept of interest in each domain, targeted the needs of Indigenous children, and met the criteria for unidimensional and invariant measurement. RESULTS: RMT results indicated moderate-fit overall fit (raw χ2 = 809, P < 0.001). This model was further improved by aggregating the five response categories into three categories. All four domains showed excellent overall fit to the Rasch model (P > 0.05), with items covering between -4.51 and 6.02 logit, with no gaps along the theoretical continua. CONCLUSION: This study provides evidence that a set of conceptually derived items was able to produce a measure that fits the Rasch model. These results aid our understanding of wellness by establishing the clinical meaning of the scale scores.

Quality of life in adolescents with heavy menstrual bleeding: Validation of the Adolescent Menstrual Bleeding Questionnaire (aMBQ).

BACKGROUND/OBJECTIVES: Heavy menstrual bleeding (HMB) affects 34% to 37% of adolescent girls. The Menstrual Bleeding Questionnaire (MBQ) is a validated measure of menstrual bleeding-specific health-related quality of life (HRQoL) for women aged ≥18 years. No similar measure existed for adolescents with HMB. PATIENTS/METHODS: HMB was defined by the Pictorial Bleeding Assessment Chart (PBAC) score ≥100. In Phase 1, a focus group of adolescents with HMB adapted the MBQ, to generate the Adolescent MBQ (aMBQ). In phase 2, participants with and without HMB were recruited from clinics and self-referral. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life module [PedsQL]©, PBAC) at two time points. Validity of the aMBQ was assessed by Pearson's correlation with the PedsQL©. Reliability was calculated using intra-class correlation (ICC) in those without HMB. The receiver operating characteristic curve assessed the aMBQ's ability to identify those with HMB. RESULTS: Phase 1 included five girls with a mean age of 17.1 (13-18) years. The aMBQ was adapted from the MBQ by substituting four words/phrases that altered 8 of the 20 questions and by adding 1 new question. The 21-item aMBQ has a score range of 0 to 77 (77 = worst HRQoL). Phase 2 included 52 participants: 20 with and 32 without HMB, with a mean age of 14.8 (11-17) years. The validity of the aMBQ was confirmed by a moderate correlation with PedsQL© (r = -0.63; P < .001). Test-retest reliability was substantial (ICC = 0.73; P = .04). An aMBQ score of >30 identified those with HMB with excellent discrimination (area under the curve = 0.82; sensitivity, 70.0%; specificity, 84.4%). CONCLUSIONS: The aMBQ is a valid and reliable tool to assess HRQoL in adolescents with HMB.

Hospitalization-Associated Disability After Cardiac Surgery in Elderly Patients　- Exploring the Risk Factors Using Machine Learning Algorithms.

Background: Hospitalization-associated disability (HAD) is associated with prolonged functional decline and increased mortality after discharge. Therefore, we examined the incidence and risk factors associated with HAD in elderly patients undergoing cardiac surgery in Japan. Methods and Results: We retrospectively examined 2,262 elderly patients who underwent elective cardiac surgery at Sakakibara Heart Institute. HAD was defined as a functional decline between time of admission and discharge measured by the Barthel Index. We analyzed clinical characteristics using machine learning algorithms to identify the risk factors associated with HAD. After excluding 203 patients, 2,059 patients remained, of whom 108 (5.2%) developed HAD after cardiac surgery. The risk factors identified were age, serum albumin concentration, estimated glomerular filtration rate, Revised Hasegawa's Dementia Scale, N-terminal pro B-type natriuretic peptide, vital capacity, preoperative Short Physical Performance Battery (SPPB) score, operation times, cardiopulmonary bypass times, ventilator times, length of postoperative intensive care unit stay, and postoperative ambulation start day. The highest incidence of HAD was found in patients with an SPPB score ≤9 and in those who started ambulation >6 days after surgery (76.9%). Conclusions: Several risk factors for HAD are components of frailty, suggesting that preoperative rehabilitation to reduce the risk of HAD is feasible. Furthermore, the association between HAD and a delayed start of ambulation reaffirms the importance of early mobilization and rehabilitation.

Family caregiver burden of patients with osteoporotic fracture in Japan.

INTRODUCTION: Osteoporotic fractures are the most common serious consequence of osteoporosis. Patients who suffer such fractures often require caregiver assistance afterwards. This study characterized the humanistic burden experienced by family caregivers of patients with osteoporotic fractures in Japan. MATERIALS AND METHODS: Family caregivers were defined as individuals who provided non-professional care to an osteoporotic fracture patient (> 50 years old). Caregivers were asked through an online survey panel about their caregiving situation, health-related quality of life (HRQoL), work impairment, and the health status of their patient. The Zarit Caregiver Burden Interview (ZBI-22), 8-item Short Form Health Survey (SF-8), and Work Productivity and Activity Impairment Caregiver version (WPAI-CG) were used to better understand the impact of osteoporotic fracture caregiving. RESULTS: Respondents (n = 309) were family caregivers who were employed (81.6%) and cared for a parent (71.5%). Over 75% of caregivers had HRQoL physical and mental component scores below 50 on SF-8. Although most patients received welfare services (78.3%), the mean ZBI-22 score was 42.2 and 57.0% of caregivers perceived their burden to be moderate or severe (ZBI-22 score ≥ 41). Over half of caregivers changed their employment status due to their caregiving responsibilities and experienced 61.4% overall work impairment. The mean productivity loss for caregivers was estimated to be over 43,000 JPY per week. CONCLUSION: The substantial humanistic and financial burden of caregiving by family members to osteoporotic fracture patients should be considered when evaluating the impact of fragility fractures, disease management and support systems for osteoporosis.

Prevalence of Type II and Type III Workplace Violence against Physicians: A Systematic Review and Meta-analysis.

BACKGROUND: Workplace violence (WPV) in the health care sector remains a prominent, under-reported global occupational hazard and public health issue. OBJECTIVE: To determine the types and prevalence of WPV among doctors. METHODS: Primary papers on WPV in medicine were identified through a literature search in 4 health databases (Ovid Medline, EMBASE, PsychoINFO and CINAHL). The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the mapping and identification of records. To assess the studies included in our review, we used the Critical Appraisal Skills Programme cohort review checklist and the Risk of Bias Assessment. RESULTS: 13 out of 2154 articles retrieved were reviewed. Factors outlining physician WPV included (1) working in remote health care areas, (2) understaffing, (3) mental/emotional stress of patients/visitors, (4) insufficient security, and (5) lacking preventative measures. The results of 6 studies were combined in a meta-analysis. The overall prevalence of WPV was 69% (95% CI 58% to 78%). CONCLUSION: The impact of WPV on health care institutions is profound and far-reaching; it is quite common among physicians. Therefore, steps must be taken to promote an organizational culture where there are measures to protect and promote the well-being of doctors.

Impact of prophylaxis on health-related quality of life of boys with hemophilia: An analysis of pooled data from 9 countries.

BACKGROUND: Prophylaxis reduces the frequency of bleeds in boys with severe hemophilia and is the standard care for their management in resource-abundant countries. The effect of prophylaxis on Health-Related Quality of Life (HRQoL) has not been established, because the sample sizes of most studies are too small to explore the relationship of multiple factors that influence HRQoL. METHODS: The aim of this study was to assess the impact of hemophilia severity and treatment regimen on HRQoL and to establish the minimum important difference (MID) using the international level of score distributions. HRQoL data were pooled from 7 studies across 9 countries. HRQoL was measured using the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT). A mixed-effect linear regression analysis was employed to assess the impact of prophylaxis on the CHO-KLAT score. RESULTS: Data from 401 boys with hemophilia were analyzed (57.6% severe hemophilia and 57.6% receiving prophylaxis). The model revealed that receiving prophylaxis was significantly associated with higher HRQoL (regression coefficient 8.5, 95% confidence interval [CI] 3.9-13.1). Boys with severe hemophilia had a significantly lower HRQoL as compared to boys with moderate and mild hemophilia whose CHO-KLAT scores were 7.0 and 6.6 points higher, respectively. There was a significant interaction between treatment and disease severity (P = 0.023), indicating prophylaxis has the most significant impact in boys with severe hemophilia. Based on these pooled data, the MID of the CHO-KLAT was established at 6.5. CONCLUSIONS: This study confirms the positive effect of prophylaxis on HRQoL in boys with hemophilia in a real-world setting and provides initial benchmarks for interpreting HRQoL scores based on use of the CHO-KLAT instrument.

Health profiles of First Nations children living on-reserve in Northern Ontario: a pooled analysis of survey data.

BACKGROUND: The Aboriginal Children's Health and Well-Being Measure (ACHWM) was developed to enable Aboriginal health leaders to gather information on the health of children at a local community level. This paper aims to describe the typical health profiles of First Nation children living on traditional territory as a reference to assist in the interpretation of ACHWM scores. METHODS: Three First Nations in Ontario, Canada, gathered health data from children using the ACHWM administered on Android tablets between 2013 and 2015. The survey data were previously analyzed to inform local health planning. These survey data were pooled to describe the distribution of ACHWM summary and quadrant scores from a larger sample and inform interpretation of ACHWM scores. RESULTS: ACHWM data from 196 participants (aged 7.6 to 21.7 yr) across 3 communities were included in the pooled sample. ACHWM summary scores ranged from 39.8 to 98.7 with a mean of 74.1 (95% confidence interval [CI] 72.5-75.7) and a maximum of 100. Strengths were reported in the spiritual (mean 78.7, 95% CI 76.7-80.8), physical (mean 77.1, 95% CI 75.1-79.0) and emotional (mean 74.4, 95% CI 72.5-76.3) quadrants. The greatest opportunity for improvement was in the mental (cognition) quadrant (mean 61.6, 95% CI 56.9-63.4). INTERPRETATION: This paper presents initial estimates for child health scores based on self-report from a large sample of First Nations children living on reserve. These results establish benchmarks to aid interpretation of the ACHWM scores in these and other communities and contexts in the future.

Health-related quality of life in Canadians with asthma: A case-control study using census data.

BACKGROUND: Asthma is a common medical condition that impacts the lives of many Canadians; yet the health-related quality of life (HRQoL) in persons with asthma relative to the general population (GP) is poorly studied. In this study, data from the Canadian Community Health Survey (CCHS) 2013 was used to quantify and compare the HRQoL of the asthmatic population (AP) and the GP. METHODS: A representative survey sample of Canadians was taken from the CCHS to compare the Health Utilities Index Mark 3 (HUI3) scores, a generic HRQoL measure, between the AP (n = 572) and the GP (n = 6518). The HUI3 multi-attribute utility (MAU) and the single-attribute utility (SAU) scores between the two sample groups were studied. The CCHS 2013 dataset was explored as the primary analysis, while the 2012 dataset was used as the confirmatory analysis to verify the consistency of the results. RESULTS: Clinically important difference was found in the MAU score between the AP and GP (p < 0.001, Effect size = 0.30). MANOVA on the eight SAU scores with post-hoc test revealed that the AP had a lower mean score of vision (p < 0.001, Effect size = 0.36) and pain/disconfort (p < 0.001, Effect size = 0.29). Those findings were consistent with the CCHS 2012 dataset result. CONCLUSIONS: These results provided evidence that in Canada, having asthma significantly worsens asthma patients' overall HRQoL and imposes significant impacts on the patients' vision and pain/discomfort. Therefore, there is room for improvement in the currently available asthma therapies so patients could achieve better HRQoL; particular focus should be given to the pain/discomfort and vision health domains.

Reliability of the Aboriginal Children's Health and Well-Being Measure (ACHWM).

PURPOSE: The aim of this research was to evaluate the reliability of the Aboriginal Children's Health and Well-Being Measure© (ACHWM). METHODS: Two cohorts of children from Wiikwemkoong Unceded Territory were recruited for this study. Each child completed the ACHWM independently on a computer tablet running a customized survey app. The data from the first and second cohorts were used to estimate the internal consistencies using Cronbach's alpha. A subgroup of the second cohort completed the survey twice, within the same day. The data from this subgroup was used to evaluate the test-retest reliability using a random effects Intra-class Correlation Coefficient (ICC). RESULTS: There were 124 participants in the first cohort and 132 participants in the second cohort. The repeated measures subgroup was comprised of 29 participants from the second cohort. The internal consistency statistic (Cronbach's alpha) was 0.93 for the first and second cohorts. The test-retest reliability ICC was 0.94 (95% CI 0.86-0.97) for the ACHWM summary scores based on the repeated measures subgroup. CONCLUSIONS: These results establish the internal consistency and the test-retest validity of the ACHWM. This important finding will enable Aboriginal communities to use this measure with confidence and promote the voices of their children in reporting their health. The ACHWM is an essential data gathering tool that enables evidence-based health care for Aboriginal communities.

A screening mechanism to recognize and support at-risk Aboriginal children.

OBJECTIVES: The Aboriginal Children's Health and Well-Being Measure© (ACHWM) was developed to assess health from the perspectives of Aboriginal children. The purpose of this paper is to document the screening process, embedded within the ACHWM, and assess its effectiveness. METHODS: The ACHWM was implemented in 2014/2015 with children 8 to 18 years of age living on the Wiikwemkoong Unceded Territory. Survey responses were screened to identify potential risk, using an automated algorithm run on computer tablets. Local mental health workers conducted brief mental health assessments to identify and support children at-risk. Data were analyzed to estimate effectiveness of this screening process. RESULTS: A total of 293 children completed the ACHWM. The screening tool identified 35% with potential risk. Mental health workers confirmed 18% of all participants as being at-risk, and all were referred for support. The sensitivity of the tool was 75% while specificity was 79%. Improvements to the screening algorithm resulted in a specificity of 97% and negative predictive value of 95%, with no loss of sensitivity. CONCLUSION: Responsible population health surveys require a process to recognize and respond to answers indicative of health risks. This paper provides an example of a screening and triage process that enabled our survey team to screen responses in real time, respond to potential risk immediately, and connect participants to local support services. This process proved essential to conducting an ethical survey. The high specificity and negative predictive value make it an effective triage tool that is particularly valuable in Aboriginal communities and with higher-risk populations.

Validity of the Aboriginal children's health and well-being measure: Aaniish Naa Gegii?

BACKGROUND: Aboriginal children experience challenges to their health and well-being, yet also have unique strengths. It has been difficult to accurately assess their health outcomes due to the lack of culturally relevant measures. The Aboriginal Children's Health and Well-Being Measure (ACHWM) was developed to address this gap. This paper describes the validity of the new measure. METHODS: We recruited First Nations children from one First Nation reserve in Canada. Participants were asked to complete the ACHWM independently using a computer tablet. Participants also completed the PedsQL. The ACHWM total score and 4 Quadrant scores were expected to have a moderate correlation of between 0.4 and 0.6 with the parallel PedsQL total score, domains (scale scores), and summary scores. RESULTS: Paired ACHWM and PedsQL scores were available for 48 participants. They had a mean age of 14.6 (range of 7 to 19) years and 60.4 % were girls. The Pearson's correlation between the total ACHWM score and a total PedsQL aggregate score was 0.52 (p = 0.0001). The correlations with the Physical Health Summary Scores and the Psychosocial Health Summary Scores were slightly lower range (r = 0.35 p = 0.016; and r = 0.51 p = 0.0002 respectively) and approached the expected range. The ACHWM Quadrant scores were moderately correlated with the parallel PedsQL domains ranging from r = 0.45 to r = 0.64 (p ≤ 0.001). The Spiritual Quadrant of the ACHWM did not have a parallel domain in the PedsQL. CONCLUSIONS: These results establish the validity of the ACHWM. The children gave this measure an Ojibway name, Aaniish Naa Gegii, meaning "how are you?". This measure is now ready for implementation, and will contribute to a better understanding of the health of Aboriginal children.

Leisure-Time Physical Activity in adults with Cerebral Palsy.

BACKGROUND: Cerebral Palsy (CP) is becoming more prevalent in the adult population, but there is limited information available regarding their Leisure-Time Physical Activity (LTPA). OBJECTIVE: To investigate the self-reported frequency and LTPA participation patterns in adults with CP, compared to the Canadian general population (CGP). METHODS: This was a cross-sectional, follow-up-survey of a cohort of 145 persons with CP. The primary outcome was the level of participation in LTPA. Questions were also posed about the motivations and self-reported barriers to LTPA participation. The survey results were compared to CGP estimates from the Canadian Community Health Survey (CCHS). RESULTS: Fifty-four participants completed the survey, and 90% reported participation in at least one LTPA per week. On average, they reported participating in LTPA 7.3 ± 5.7 times/week. They also reported participating in an average of 4.1 ± 2.4 different types of LTPA. Walking, home-exercise, and swimming were the most frequently reported as a primary LTPA in the CP sample. These finding were comparable to those from the CGP. However, adults with CP were more likely to participate in home-exercise than the CGP (p < 0.05). More than 40% reported that the purpose of their LTPA was fitness or body maintenance and 56% indicated an interest in starting new activities. Various barriers were also reported. CONCLUSIONS: Adults with CP frequently participated in LTPA. However, the majority of them are not achieving recommended daily physical activity levels. Also their LTPA habitually focuses on rehabilitative exercises and the diversity of LTPA is limited by several barriers.

Changes in gross motor function and health-related quality of life in adults with cerebral palsy: an 8-year follow-up study.

OBJECTIVE: To describe changes in gross motor function and health-related quality of life (HRQOL) in adults with cerebral palsy (CP). DESIGN: An 8-year follow-up survey. SETTING: Participants who completed the baseline survey in 2003 were invited. PARTICIPANTS: The sample of adults with CP (N=54; response rate=37%) included a "younger group" (group 1; n=31; age, 23-27y; 15 women) and an "older group" (group 2; n=23; age, 33-42y; 10 women). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Gross Motor Function Classification System (GMFCS), Self-Rated Health (SRH), the Health Utility Index Mark III (HUI3), and the Assessment of Quality of Life (AQoL). RESULTS: Eight years after the initial survey, 27% of the participants in the combined group had deteriorations on the GMFCS, 52% on the SRH, 44% on the HUI3, and 25% on the AQoL. Members of group 1 reported stable scores as they made the transition to adulthood, while many of the group 2 members experienced declines, with relative risk of 1.47 (95% confidence interval [CI], 0.16-2.24) on the GMFCS, 1.36 (95% CI, 0.83-2.23) on the SRH, 1.19 (95% CI, 0.66-2.15) on the HUI3, and 3.17 (95% CI, 1.12-9.00) on the AQoL. CONCLUSIONS: Although much attention has focused on the transitions of persons with CP during their late teens and early 20s, this research found that deteriorations in the GMFCS levels and the HRQOL were most evident in adults in their late 20s and 30s. More detailed longitudinal studies are required to evaluate the longer-term health outcomes among persons with CP into their 30s and beyond.