Summarizing activity limitations in children with chronic illnesses living in the community: a measurement study of scales using supplemented interRAI items

<p>Abstract</p> <p>Background</p> <p>To test the validity and reliability of scales intended to measure activity limitations faced by children with chronic illnesses living in the community. The scales were based on information provided by caregivers to service program personnel almost exclusively trained as social workers. The items used to measure activity limitations were interRAI items supplemented so that they were more applicable to activity limitations in children with chronic illnesses. In addition, these analyses may shed light on the possibility of gathering functional information that can span the life course as well as spanning different care settings.</p> <p>Methods</p> <p>Analyses included testing the internal consistency, predictive, concurrent, discriminant and construct validity of two activity limitation scales. The scales were developed using assessment data gathered in the United States of America (USA) from over 2,700 assessments of children aged 4 to 20 receiving Medicaid Early and Periodic Screening, Diagnostic and Treatment (EPSDT) services, specifically Personal Care Services to assist children in overcoming activity limitations. The Medicaid program in the USA pays for health care services provided to children in low-income households. Data were collected in a single, large state in the southwestern USA in late 2008 and early 2009. A similar sample of children was assessed in 2010, and the analyses were replicated using this sample.</p> <p>Results</p> <p>The two scales exhibited excellent internal consistency. Evidence on the concurrent, predictive, discriminant, and construct validity of the proposed scales was strong. Quite importantly, scale scores were not correlated with (confounded with) a child's developmental stage or age. The results for these scales and items were consistent across the two independent samples.</p> <p>Conclusions</p> <p>Unpaid caregivers, usually parents, can provide assessors lacking either medical or nursing training with reliable and valid information on the activity limitations of children. One can summarize these data in scales that are both internally consistent and valid. Researchers and clinicians can use supplemented interRAI items to provide guidance for professionals and programs serving children, as well as older persons. This research emphasizes the importance of developing medical information systems that allow one to integrate information not only across care settings but also across an individual's life course.</p

Disease characteristics of MCT8 deficiency : an international, retrospective, multicentre cohort study

Background Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies

Effectiveness of antiepileptic therapy in patients with PCDH19 mutations

Purpose PCDH19 mutations cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life, epilepsy is known to be highly pharmacoresistant. The aim of our study was to evaluate the effectiveness of antiepileptic therapy in patients with PCDH19 mutations. Methods We report a retrospective multicenter study of antiepileptic therapy in 58 female patients with PCDH19 mutations and epilepsy aged 2-27 years (mean age 10.6 years). Results The most effective drugs after 3 months were clobazam and bromide, with a responder rate of 68% and 67%, respectively, where response was defined as seizure reduction of at least 50%. Defining long-term response as the proportion of responders after 12 months of treatment with a given drug in relation to the number of patients treated for at least 3 months, the most effective drugs after 12 months were again bromide and clobazam, with a long-term response of 50% and 43%, respectively. Seventy-four percent of the patients became seizure-free for at least 3 months, 47% for at least one year. Significance The most effective drugs in patients with PCDH19 mutations were bromide and clobazam. Although epilepsy in PCDH19 mutations is often pharmacoresistant, three quarters of the patients became seizure-free for at least for 3 months and half of them for at least one year. However, assessing the effectiveness of the drugs is difficult because a possible age-dependent spontaneous seizure remission must be considered

Long-term efficacy of T3 analogue triac in children and adults with MCT8 deficiency: a real-life retrospective cohort study

Context Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency