Body Mass Index (BMI) is widely used to assess the impact of obesity on cardiometabolic risk in children but it does not always relate to central obesity and varies with growth and maturation. ...Waist-to-Height Ratio (WHtR) is a relatively constant anthropometric index of abdominal obesity across different age, sex or racial groups. However, information is scant on the utility of WHtR in assessing the status of abdominal obesity and related cardiometabolic risk profile among normal weight and overweight/obese children, categorized according to the accepted BMI threshold values.
Cross-sectional cardiometabolic risk factor variables on 3091 black and white children (56% white, 50% male), 4-18 years of age were used. Based on the age-, race- and sex-specific percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles) and overweight/obese (≥ 85th percentile). The risk profiles of each group based on the WHtR (<0.5, no central obesity versus ≥ 0.5, central obesity) were compared.
9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5) and 19.8% among the overweight/obese were not (WHtR < 0.5). On multivariate analysis the normal weight centrally obese children were 1.66, 2.01, 1.47 and 2.05 times more likely to have significant adverse levels of LDL cholesterol, HDL cholesterol, triglycerides and insulin, respectively. In addition to having a higher prevalence of parental history of type 2 diabetes mellitus, the normal weight central obesity group showed a significantly higher prevalence of metabolic syndrome (p < 0.0001). In the overweight/obese group, those without central obesity were 0.53 and 0.27 times less likely to have significant adverse levels of HDL cholesterol and HOMA-IR, respectively (p < 0.05), as compared to those with central obesity. These overweight/obese children without central obesity also showed significantly lower prevalence of parental history of hypertension (p = 0.002), type 2 diabetes mellitus (p = 0.03) and metabolic syndrome (p < 0.0001).
WHtR not only detects central obesity and related adverse cardiometabolic risk among normal weight children, but also identifies those without such conditions among the overweight/obese children, which has implications for pediatric primary care practice.
Summary Background Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is ...frequently assumed but has rarely been reported. Our aim was to test this association. Methods We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. Findings Of 22 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2–7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94–1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95–1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10–1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r =−0·06 and r =−0·02). Interpretation The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. Funding Deutsche Forschungsgemeinschaft.
Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by mutations in the gene encoding alpha-galactosidase A, resulting in lysosomal accumulation of globotriaosylceramide and other ...glycosphingolipids. Early detection of FD is challenging, accounting for delayed diagnosis and treatment initiation. This study aimed to develop an algorithm using a logistic regression model to facilitate early identification of patients based on ICD-10-GM coding using a German Sickness Fund Database. The logistic regression model was fitted on a binary outcome variable based on either a treated FD cohort or a control cohort (without FD). Comorbidities specific to the involved organs were used as covariates to identify potential FD patients with ICD-10-GM E75.2 diagnosis but without any FD-specific medication. Specificity and sensitivity of the model were optimized to determine a likely threshold. The cut-point with the largest values for the Youden index and concordance probability method and the lowest value for closest to (0,1) was identified as 0.08 for each respective value. The sensitivity and specificity for this cut-point were 80.4% and 79.8%, respectively. Additionally, a sensitivity analysis of the potential FD patients with at least two codes of E75.2 diagnoses was performed. A total of 284 patients were identified in the potential FD cohort using the logistic regression model. Most potential FD patients were < 30 years old and female. The identification and incidence rates of FD in the potential FD cohort were markedly higher than those of the treated FD cohort. This model serves as a tool to identify potential FD patients using German insurance claims data.
The systematic collection of disease-specific symptoms and impacts on the lives of patients with Fabry Disease (FD) can offer unique insights into the patient experience, yet no disease-specific tool ...to measure FD symptoms exists. This study describes the development of the Fabry Disease Patient-Reported Outcome (FD-PRO).
A targeted literature search, interviews with key opinion leaders (KOLs), and concept elicitation (CE) interviews with patients identified the most frequent signs and symptoms associated with FD and their impact on daily life. Cognitive interviews evaluated patients' ability to understand the FD-PRO instructions and respond to the items on the draft FD-PRO instrument.
The targeted literature search identified key signs and symptoms in domains that were confirmed in KOL interviews. In CE interviews with 37 treated and treatment-naïve patients, neuropathic pain symptoms (95% treated, 82% treatment-naïve), temperature intolerance (95% treated, 88% treatment-naïve), energy difficulties (95% treated, 94% treatment-naïve), hearing/vision impairment (95% treated, 71% treatment-naïve), and gastrointestinal symptoms (80% treated, 59% treatment-naïve) were most frequently mentioned. Results were similar for men and women in both treated and treatment-naïve groups. While treatment-naïve patients in general expressed fewer and milder symptoms compared to treated patients, the overall sets of symptoms expressed by the two groups were similar. The most severe symptoms were neuropathic pain, stomach pain, burning pain, and fatigue. The most bothersome symptoms were stomach pain, breathing difficulty, fatigue, neuropathic pain, and constipation. The most frequent impacts were in the work/school limitations domain for both treated and treatment-naïve patients. The impacts with the highest difficulty ratings were stress, limited outdoor activity, and guilt. Cognitive interviews with 14 treated and treatment-naïve patients resulted in the refinement of FD-PRO items and language.
The FD-PRO is a novel, disease-specific instrument that measures the patient experience in Fabry disease. Such tools are valuable in capturing the burden of disease in patients with FD and demonstrating the value of treatment in clinical trials.
Haemophilia bears substantial humanistic and economic burden on children and their caregivers. Characterising the differential impact of severe versus moderate paediatric haemophilia is important for ...clinical and health policy decisions. We analysed health-related quality of life (HRQoL), annual direct medical (excluding factor treatment costs), non-medical and societal costs among children and adolescents with moderate and severe haemophilia A or B without inhibitors from the European CHESS-PAEDs study. Information was reported by physicians and caregivers; patients aged ≥ 8 years self-reported their HRQoL. Descriptive statistics summarised demographic and clinical characteristics, costs, and HRQoL scores (EQ-5D-Y). Regression models estimated differences in HRQoL and costs for moderate versus severe haemophilia adjusting for age, body mass index z-score, country, number of comorbidities, and weight-adjusted annual clotting factor consumption.
The analytic sample comprised 794 patients with a mean age of 10.5 years; most had haemophilia A (79%) and 58% had severe haemophilia. Mean predicted direct medical costs in moderate patients were two-thirds of the predicted costs for severe disease (€3065 vs. €2047; p < 0.001; N = 794), while societal costs were more than half of the predicted costs for children with severe haemophilia (€6950 vs. €3666; p < 0.001; N = 220). Mean predicted HRQoL scores were 0.74 and 0.69 for moderate and severe disease, respectively (p < 0.05; N = 185).
Children with haemophilia and their caregivers displayed a significant economic and humanistic burden. While severe patients showed the highest direct medical and societal costs, and worse HRQoL, the burden of moderate haemophilia on its own was substantial and far from negligible.
Late-onset Pompe disease (LOPD) is a rare genetic disorder due to the absence or deficiency of acid alpha-glucosidase enzyme resulting in slowly progressing reduction of muscle strength, causing ...difficulties with mobility and respiration. Wearable technologies offer novel options to evaluate mobility in a real-world setting. LOPD patients self-reporting LOPD, ≥18 years, US residents, walking (with or without aid), and not on invasive ventilation were recruited for a 6- to 8-week wearable study via patient organizations. Eligible patients were shipped a wearable tracker (Fitbit One™) and completed self-assessment questionnaires. Mobility outcome measures were median step count and peak 1-min activity. In the analyses cohort (
= 29), engagement in data sharing was high (94% of patients uploaded data for more than half the study days). Mean age was 43 years, 90% were females, and 93% were diagnosed in adulthood. Mean delay in diagnosis was 10 years; most had disease onset for ≥10 years (55%); some required walking aid (17%) and breathing assistance (38%). Mean step count differed by age (20-39 years: 4071 vs. 40-69 years: 2394,
< 0.01), diagnostic delay (<10 years: 3584 vs. ≥10 years: 2232,
< 0.05), disease duration (<10 years: 4219 vs. ≥10 years: 2462,
< 0.05), and ambulatory status (aided: 1883 vs. unaided: 3408,
< 0.05). Patient-reported "fatigue and pain" score was inversely correlated with step count (Pearson's
= -0.42,
< 0.05) and peak 1-min activity (Pearson's
= -0.49,
< 0.01). This study illustrates a new approach to measure mobility in LOPD patients and establishes a framework for future outcomes data collection.
As activity tracking devices become smaller, cheaper, and more consumer-accessible, they will be used more extensively across a wide variety of contexts. The expansion of activity tracking and ...personal data collection offers the potential for patient engagement in the management of chronic diseases. Consumer wearable devices for activity tracking have shown promise in post-surgery recovery in cardiac patients, pulmonary rehabilitation, and activity counseling in diabetic patients, among others. Unfortunately, the data generated by wearable devices is seldom integrated into programmatic self-management chronic disease regimens. In addition, there is lack of evidence supporting sustained use or effects on health outcomes, as studies have primarily focused on establishing the feasibility of monitoring activity and the association of measured activity with short-term benefits.
Monitoring devices can make a direct and real-time impact on self-management, but the validity and reliability of measurements need to be established. In order for patients to become engaged in wearable data gathering, key patient-centered issues relating to usefulness in care, motivation, the safety and privacy of information, and clinical integration need to be addressed. Because the successful usage of wearables requires an ability to comprehend and utilize personal health data, the user experience should account for individual differences in numeracy skills and apply evidence-based behavioral science principles to promote continued engagement.
Activity monitoring has the potential to engage patients as advocates in their personalized care, as well as offer health care providers real world assessments of their patients' daily activity patterns. This potential will be realized as the voice of the chronic disease patients is accounted for in the design of devices, measurements are validated against existing clinical assessments, devices become part of the treatment 'prescription', behavior change programs are used to engage patients in self-management, and best practices for clinical integration are defined.
Objective
This pilot study tested a course-based intervention to help people with multiple sclerosis (MS) match their daily activity to symptom severity (“sweet spot”) using wearable activity ...trackers.
Methods
This two-phase study recruited online research network members reporting MS and who were utilizing Fitbit One™ activity trackers. In the first phase, participant interviews assessed demand based on physical activity and the use of behavior-change techniques. The second phase assessed the demand, limited efficacy, acceptability, and practicality of a “Wearables 101” course that integrated behavior change and self-experimentation principles. Tracker data were used to determine the percent of matches between daily symptom-based step goals and step counts.
Results
Participants expressed demand in the form of interest in gaining insights about a possible “sweet spot” behavioral target, if a system could be produced to support that. Limited efficacy results were mixed, with approximately one-third of participants dropping out and only half matching their daily target goals for at least 50% of days. In terms of practicality, participants commented on the burden of daily measurement and the need for a longer baseline period. Participants noted that tracking helped support an understanding of the link between activities and symptom severity, suggesting acceptability.
Conclusions
Results suggested that the intervention demand and acceptability criteria were demonstrated more strongly than limited efficacy and practicality. The matching intervention tested in this study will require refinement in baseline measurement, goal definition, and reduced data-gathering burden. Such changes may improve efficacy and practicality requirements and, by extension, later impact of the intervention on MS outcomes. Overall, these results provide justification for additional work on refining the intervention to increase practicality and efficacy.
Fabry disease (FD) is a rare, genetic disease, that if untreated, progresses to irreversible and life-threatening renal, cardiac, and cerebrovascular events. FD symptoms impact daily functioning and ...quality of life, but no disease-specific measure of these symptoms has been psychometrically tested.
The Fabry Disease Patient-Reported Outcome (FD-PRO) consists of 19 items that measure neuropathic symptoms (pain, tingling, numbness and burning in upper/lower extremities), headache, abdominal pain, heat intolerance, swelling, tinnitus, fatigue, hearing/vision impairment, hypohidrosis (diminished sweating) and difficulty engaging in regular physical activities in the past 24 h. Measurement properties of the instrument were evaluated among 139 adult (≥ 18 years) FD diagnosed patients (enzyme deficiency in males; GLA genotyping in females) including enzyme replacement (ERT) treated or treatment-naïve patients, classic or late-onset phenotypes from ten countries and eighteen sites. Patients completed the FD-PRO daily on a handheld electronic diary for 4 weeks; demographic, other patient and clinician reported outcomes were also collected.
The mean age of patients was 43 years; with even sex distribution (female: 53%) and majority was ERT treated (72%). Patient compliance was high; ≥ 87% completed at least 4 FD-PRO entries each week (mean completion time: < 3 min in week one). Empirical evaluation of item properties via inter-item correlations, exploratory factor analysis and item-response theory models suggested that a total symptom score (TSS) could be calculated. Due to redundancy among items, a “neuropathy parcel” and an “audiovisual parcel” were created in generating the TSS (items within a parcel averaged and treated as a single item). Two items were excluded from TSS: sweating (did not correlate with other items) and difficulty engaging in regular physical activities (measure of impact, not symptoms). Internal consistency (Cronbach's alpha) of the TSS was ≥0.89 across weeks; test-retest reliability (intraclass correlation coefficient) was ≥0.91. The TSS was correlated with conceptually similar clinical and patient reported assessments as expected (r > |0.4|) and discriminated moderate/severe from least severe FD groups in known-groups validity analyses.
The FD-PRO instrument is a novel disease-specific instrument that assesses classic and non-classic symptoms, with strong psychometric properties and appropriate for use in clinical studies.
Understanding the risk for type 2 diabetes (T2D) early in the life course is important for prevention. Whether genetic information improves prediction models for diabetes from adolescence into ...adulthood is unknown.
With the use of data from 1030 participants in the Bogalusa Heart Study aged 12 to 18 followed into middle adulthood, we built Cox models for incident T2D with risk factors assessed in adolescence (demographics, family history, physical examination, and routine biomarkers). Models with and without a 38 single-nucleotide polymorphism diabetes genotype score were compared by C statistics and continuous net reclassification improvement indices.
Participant mean (± SD) age at baseline was 14.4 ± 1.6 years, and 32% were black. Ninety (8.7%) participants developed T2D over a mean 26.9 ± 5.0 years of follow-up. Genotype score significantly predicted T2D in all models. Hazard ratios ranged from 1.09 per risk allele (95% confidence interval 1.03-1.15) in the basic demographic model to 1.06 (95% confidence interval 1.00-1.13) in the full model. The addition of genotype score did not improve the discrimination of the full clinical model (C statistic 0.756 without and 0.760 with genotype score). In the full model, genotype score had weak improvement in reclassification (net reclassification improvement index 0.261).
Although a genotype score assessed among white and black adolescents is significantly associated with T2D in adulthood, it does not improve prediction over clinical risk factors. Genetic screening for T2D in its current state is not a useful addition to adolescents' clinical care.
PDF
