Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM Study.

OBJECTIVES: The primary objective was to investigate whether nonadherence to antiepileptic drugs (AEDs) is associated with increased mortality and the secondary objective to examine whether nonadherence increases the risk of serious clinical events, including emergency department (ED) visits, hospitalizations, motor vehicle accident (MVA) injuries, fractures, and head injuries. METHODS: A retrospective open-cohort design was employed using Medicaid claims data from Florida, Iowa, and New Jersey from January 1997 through June 2006. Patients aged > or =18 years with > or =1 diagnosis of epilepsy by a neurologist and > or =2 AED pharmacy dispensings were selected. Medication possession ratio (MPR) was used to evaluate AED adherence on a quarterly basis with MPR > or =0.80 considered adherent and <0.80 nonadherent. The association of nonadherence with mortality was assessed using a time-varying Cox regression model adjusting for demographic and clinical confounders. Incidence rates for serious clinical events were compared between adherent and nonadherent quarters using incidence rate ratios (IRRs) with 95% CIs calculated based on the Poisson distribution. RESULTS: The 33,658 study patients contributed 388,564 AED-treated quarters (26% nonadherent). Nonadherence was associated with an over threefold increased risk of mortality compared to adherence (hazard ratio = 3.32, 95% CI = 3.11-3.54) after multivariate adjustments. Time periods of nonadherence were also associated with a significantly higher incidence of ED visits (IRR = 1.50, 95% CI = 1.49-1.52), hospital admissions (IRR = 1.86, 95% CI = 1.84-1.88), MVA injuries (IRR = 2.08, 95% CI = 1.81-2.39), and fractures (IRR = 1.21, 95% CI = 1.18-1.23) than periods of adherence. CONCLUSION: These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.

Additional N-glycosylation and its impact on the folding of intestinal lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase (LPH) is a membrane bound intestinal hydrolase, with an extracellular domain comprising 4 homologous regions. LPH is synthesized as a large polypeptide precursor, pro-LPH, that undergoes several intra- and extracellular proteolytic steps to generate the final brush-border membrane form LPHbeta(final). Pro-LPH is associated through homologous domain IV with the membrane through a transmembrane domain. A truncation of 236 amino acids at the COOH terminus of domain IV (denoted LAC236) does not significantly influence the transport competence of the generated mutant LPH1646MACT (Panzer, P., Preuss, U., Joberty, G., and Naim, H. Y. (1998) J. Biol. Chem. 273, 13861-13869), strongly suggesting that LAC236 is an autonomously folded domain that links the ectodomain with the transmembrane region. Here, we examine this hypothesis by engineering several N-linked glycosylation sites into LAC236. Transient expression of the cDNA constructs in COS-1 cells confirm glycosylation of the introduced sites. The N-glycosyl pro-LPH mutants are transported to the Golgi apparatus at substantially reduced rates as compared with wild-type pro-LPH. Alterations in LAC236 appear to sterically hinder the generation of stable dimeric trypsin-resistant pro-LPH forms. Individual expression of chimeras containing LAC236, the transmembrane domain and cytoplasmic tail of pro-LPH and GFP as a reporter gene (denoted LAC236-GFP) lends strong support to this view: while LAC236-GFP is capable of forming dimers per se, its N-glycosyl variants are not. The data strongly suggest that the LAC236 is implicated in the dimerization process of pro-LPH, most likely by nucleating the association of the ectodomains of the enzyme.

Variability in the timing of repeat screening mammography.

BACKGROUND: Although numerous studies have examined repeat mammography, they provide limited information about actual patterns of women's behavior over time. METHODS: In this study, 128 asymptomatic women ages 50 to 75 who had had their first mammograms 15 to 27 months previously were interviewed to determine rates of repeat mammography. Eighty-six of these women were HMO members; the remaining 42 were nonmembers. RESULTS: In both subpopulations, repeat mammography rates were low among women interviewed less than 21 months after their first mammogram, but much higher among those interviewed 21 months or more afterward. CONCLUSIONS: These data suggest that waiting up to 2 years to have a second mammogram may be at least as common a choice as having it after 1 year. It is of particular interest that this was found in a population of HMO members who receive reminders and vouchers for free mammograms annually.

Costs vs quality in different types of primary care settings.

OBJECTIVE: To determine the relationship between efficiency in use of resources and quality of care provided by physicians serving as the usual source of care for patients in a state Medicaid program. DESIGN: Retrospective quality-of-care review of 2024 outpatient medical records of 135 providers sampled from system-wide Medicaid claims data in Maryland. SUBJECTS: Providers in three types of practice settings (hospital outpatient clinic, community health center, and physician's office) were stratified into three case mix-adjusted resource use groups (high, medium, and low). A sample of patients with the diagnoses of diabetes, hypertension, asthma, well-child care, or otitis media were identified from Medicaid claims forms from visits during 1988. Case mix was controlled by the application of the ambulatory care groups, a method that characterizes populations according to their burden of morbidity. MAIN OUTCOME MEASURES: Nurses from the local peer review organization audited medical records using explicit criteria for quality of care in several categories: evidence of impaired access, evidence of compromised technical quality, evidence of inappropriate care, outcome of care, and several generic indicators of quality. Well-adult care was assessed for patients with the adult diagnoses. RESULTS: Although there were some systematic differences by type of facility in some aspects of quality of care (more access problems for patients in hospital clinics and more technical quality problems for patients in office-based practice), there were no consistent differences in quality of care overall for patients in different types of settings and no consistent relationships between cost-efficiency and quality of care. However, patients in medium-cost community health centers had the best or second best scores for most of the 21 comparisons of type of quality assessed. CONCLUSIONS: Quality of care provided for common conditions in primary care is not associated with costs generated by providers. Policies directed toward the choice of low-cost vs high-cost providers will not necessarily lead to a deterioration in the quality of care. States can both improve quality and lower costs by consistent monitoring of programs over time. The finding of generally higher quality of care for patients in medium-cost community health centers deserves further study.

Osteopathia striata syndrome. Clinical, genetic and radiologic considerations.

Osteopathia striata, an autosomal dominant disorder, has been diagnosed in a 19-year-old mildly retarded woman. In addition, she has macrocephaly, a leonine facies, disfigurement of the lower jaw, a cleft palate and mixed hearing loss. Roentgenograms of the skull and long bones show thickening of the calvarium, particularly at the base, mandibular hyperplasia, and striations in the long bones and pelvis. Except for the cleft palate, which has not been previously reported, and the retardation, which appears to be quite uncommon in this condition, these findings are characteristic of osteopathia striata. Because the disorder may resemble several other conditions, the differential diagnosis should include osteopoikilosis, the autosomal dominant form of osteopetrosis, and hyperostosis corticalis generalisata.