Clinical course correlates poorly with muscle pathology in nemaline myopathy

Objective: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy. Methods: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to alpha-actin (ACTA1) mutations and three with mutations in alpha-tropomyosin(SLOW) (TPM3). For each biopsy rod number per fiber, percentage of fibers with rods, fiber-type distribution of rods, and presence or absence of intranuclear rods were documented. Results: Rods were present in all skeletal muscles and diagnosis was possible at all ages. Most biopsies contained nemaline bodies in more than 50% of fibers, although rods were seen only on electron microscopy in 10 patients. Rod numbers and localization correlated poorly with clinical severity. Frequent findings included internal nuclei and increased fiber size variation, type 1 fiber predominance and atrophy, and altered expression of fiber type specific proteins. Marked sarcomeric disruption, increased glycogen deposition, and intranuclear rods were associated with more severe clinical phenotypes. Serial biopsies showed progressive fiber size variation and increasing numbers of rods with time. Pathologic findings varied widely in families with multiple affected members. Conclusions: Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal alpha-actin. Nemaline myopathy due to mutations in alpha-tropomyosin(SLOW) was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype

Evidence on Interventions to Reduce Medical Errors: An Overview and Recommendations for Future Research

OBJECTIVE: To critically review the existing evidence on interventions aimed at reducing errors in health care delivery. DESIGN: Systematic review of randomized trials on behavioral, educational, informational and management interventions relating to medical errors. Pertinent studies were identified from MEDLINE, EMBASE, the Cochrane Clinical Trials Registry, and communications with experts. SETTING: Both inpatients and outpatients qualified. No age or disease restrictions were set. MEASUREMENTS: Outcomes were medical errors, including medication, prescription, and diagnostic errors, and excluding preventive medicine errors and simple ordering of redundant tests. MAIN RESULTS: Thirteen randomized studies qualified for evaluation. The trials varied extensively in their patient populations (mean age, 2 weeks to 83 years), study setting, definition of errors, and interventions. Most studies could not afford masking and rigorous allocation concealment. In 9 of 13 studies, error rates in the control arms were very high (10% to 63%), and large treatment benefits from the studied interventions were demonstrated for the main outcome. Interventions were almost always effective in a sample of 24 nonrandomized studies evaluated for comparison. Actual patient harm from serious errors was rarely recorded. CONCLUSIONS: Medical errors were very frequent in the studies we identified, arising sometimes in more than half of the cases where there is an opportunity for error. Relatively simple interventions may achieve large reductions in error rates. Evidence on reduction of medical errors needs to be better categorized, replicated, and tested in study designs maximizing protection from bias. Emphasis should be placed on serious errors