Children With Chronic Pain: Response Trajectories After Intensive Pain Rehabilitation Treatment

Intensive pain rehabilitation programs for children with chronic pain are effective for many patients. However, characteristics associated with treatment response have not been well documented. In this article we report trajectories of pain and functional impairment in patients with chronic pain up to 1 year after intensive pain rehabilitation and examine baseline factors associated with treatment response. Patients (n?=?253) with chronic pain and functional disability were assessed at 5 time points (admission, discharge, 1-month, 4-month, and 12-month follow-ups). Individual trajectories were empirically grouped using SAS PROC TRAJ. For functional disability, 2 groups emerged: treatment responders (88%) and nonresponders (12%). Using a binomial logistic regression model to predict disability trajectory group, no baseline variables were significant predictors for the disability trajectory group. For pain, 3 groups emerged: early treatment responders (35%), late treatment responders (38%), and nonresponders (27%). Using multinomial regression analyses to predict pain trajectory group, older age, higher pain scores, fewer social difficulties, higher anxiety levels, and lower readiness to change were characteristics that distinguished nonresponders from responders; no significant predictors distinguished the late responders from the early responders. These results provide key information on the baseline factors that influence intensive pain rehabilitation outcomes, including risk factors that predict treatment nonresponse. Our findings have implications for developing more targeted treatment interventions.

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC,PAX6 and CYP1B1

Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/microphthalmia.