Stephen C. Alder

Efficacy of the Ketogenic Diet as a Treatment Option for Epilepsy: Meta-analysis:

The evidence base for the efficacy of the ketogenic diet was assessed among pediatric epileptic patients by application of a rigorous statistical meta-analysis. Nineteen studies from 392 abstracts met the inclusion criteria. The sample size was 1084 patients (mean age at initiation 5.78 ± 3.43 years). The pooled odds ratio, using a random effects model, of treatment success (> 50% seizure reduction) among patients staying on the diet relative to those discontinuing the diet was 2.25 (95% confidence interval = 1.69—2.98). The reasons for diet discontinuation included < 50% seizure reduction (47.0%), diet restrictiveness (16.4%), and incurrent illness or diet side effects (13.2%). The results indicate that children with generalized seizures and patients who respond with > 50% seizure reduction within 3 months tend to remain on the diet longer. Although no class I or II studies have been published regarding the efficacy of the ketogenic diet, this meta-analysis shows that current observational studies reporting on the therapeutic effect of the ketogenic diet contain valuable statistical data. Future observational studies should aim for long-term follow-up, patient dropout analysis, and improved seizure type characterization. (J Child Neurol 2006;21:193—198; DOI 10.2310/7010.2006.00044).

Children Who Recover from Early Stunting and Children Who Are Not Stunted Demonstrate Similar Levels of Cognition

Stunting is associated with adverse cognitive development in childhood and adolescence, fewer years of schooling, decreased productivity, and reduced adult stature. Recovery from early stunting is possible; however, few studies explore whether those who demonstrate linear catch-up growth experience long-term cognitive deficits. Using longitudinal data on 1674 Peruvian children from the Young Lives study, we identified factors associated with catch-up growth and assessed whether children who displayed catch-up growth have significantly lower cognition than children who were not stunted during infancy and childhood. Based on anthropometric data for children 6-18 mo of age and again for the same children when they were 4.5-6 y of age, we categorized participants as not stunted, stunted in infancy but not childhood (catch-up), stunted in childhood, and stunted in infancy and childhood. Children who had grandparents in the home, had less severe stunting in infancy, and had taller mothers were more likely to demonstrate catch-up growth by round 2. Children who experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted (P = 0.6 and P = 0.7, respectively). Those stunted in childhood as well as those stunted in infancy and childhood scored significantly lower on both assessments than children who were not stunted. Based on findings from this study, policy makers and program planners should consider redoubling efforts to prevent stunting and promote catch-up growth over the first few years of life as a way of improving childrens physical and intellectual development.

Associations between body-mass index and surgery for rotator cuff tendinitis.

BACKGROUND Rotator cuff tendinopathy is a common entity. We hypothesized that obesity, because of biomechanical and systemic risk factors, increases the risks of rotator cuff tendinitis, tears, and related surgical procedures. METHODS A frequency-matched case-control study was conducted. Three hundred and eleven patients who were fifty-three to seventy-seven years old and who underwent rotator cuff repair, arthroscopy, and/or other repair of the shoulder in a large hospital from 1992 to 2000 were included in the study. These surgical procedures were used as proxies for the risk of rotator cuff tendinitis. These patients were age and frequency-matched to 933 controls, who were randomly drawn from a pool of 10,943 potential controls consisting of Utah state residents who were enrolled in a large cancer-screening trial. Age-adjusted odds ratios were calculated with use of the International Classification of Diseases, Ninth Revision procedural codes and body-mass-index groups. The data were stratified according to gender and age. Multiple linear regression analyses also were performed. RESULTS There was an association between increasing body-mass index and shoulder repair surgery. The highest odds ratios for both men (odds ratio = 3.13; 95% confidence interval = 1.29 to 7.61) and women (odds ratio = 3.51; 95% confidence interval = 1.80 to 6.85) were for individuals with a body-mass index of > or =35.0 kg/m(2). Tests for trend also were highly significant for both men (p = 0.002) and women (p < or = 0.001). Multiple linear regression analysis also indicated a significant association between increasing body-mass index and shoulder surgery (beta = 1.57; 95% confidence interval = 0.97 to 2.17; p < or = 0.001). CONCLUSIONS There is an association between obesity and shoulder repair surgery in men and women who are fifty-three to seventy-seven years of age. The results of the present study suggest that increasing body-mass index is a risk factor for rotator cuff tendinitis and related conditions.

High Dose Brachytherapy as Monotherapy for Intermediate Risk Prostate Cancer

PURPOSE We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. MATERIALS AND METHODS Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. RESULTS Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. CONCLUSIONS High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%.

Impact of early and concurrent stunting on cognition

Undernutrition is associated with poor cognitive development, late entry into school, decreased years of schooling, reduced productivity and smaller adult stature. We use longitudinal data from 1674 Peruvian children participating in the Young Lives study to assess the relative impact of early stunting (stunted at 6-18 months of age) and concurrent stunting (stunted at 4.5-6 years of age) on cognitive ability. Anthropometric data were longitudinally collected for children at 6-18 months of age and 4.5-6 years of age at which time verbal and quantitative ability were also assessed. We estimate that an increase in concurrent height-for-age z-scores (HAZ) by one standard deviation was associated with an increase in a childs score on the Peabody Picture Vocabulary Test (PPVT) by 2.35 points [confidence interval (CI): 1.55-3.15] and a 0.16 point increase on the cognitive development assessment (CDA) (CI: 0.05-0.27). Furthermore, we report that the estimate for concurrent HAZ and PPVT is significantly higher than the estimate for early stunting and PPVT. We found no significant difference between early and concurrent estimates for HAZ and CDA. Children from older mothers, children whose mothers had higher education levels, children living in urban areas, children who attended pre-school, children with fewer siblings and children from wealthier backgrounds scored higher on both assessments. Cognitive skills of children entering school were associated with early stunting but the strongest association was found with concurrent stunting suggesting that interventions preventing linear growth faltering should not only focus on the under 2s but include children up to 5 years of age.

Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: A reevaluation based on corrected dosimetry and examination data

Background: A study was begun in 1965 to 1966 to determine whether children exposed to radioactive iodine from nuclear weapons testing at the Nevada Test Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we reported that among those examined in 1985 to 1986 (Phase II) there was an association between radiation from the Nevada Test Site and thyroid neoplasms. Methods: We reevaluated the relationship between exposure to Nevada Test Site fallout and thyroid disease using newly corrected dose estimates and disease outcomes from the Phase II study. A prospective cohort of school children 12 to 18 years old living in Utah, Nevada, and Arizona was first examined for thyroid disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report, 2497 subjects formed the basis for this analysis. Thyroid disease, including thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk ratios (RRs) with a dose–response expressed as excess risk ratio (ERR/Gy). Results: The RR between thyroid radiation dose in the highest dose group and thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to estimate risk. Conclusions: Persons exposed to radioactive iodine as children have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30 years after exposure.

A Multifaceted Intervention to Improve Antimicrobial Prescribing for Upper Respiratory Tract Infections in a Small Rural Community

BACKGROUND Antibiotic prescribing for upper respiratory tract infections (URTIs) is widespread, is often inappropriate, and may contribute to antibiotic resistance among community-acquired pathogens, such as Streptococcus pneumoniae. METHODS A multifaceted intervention involving health care professionals and patients was introduced to a small rural Utah community and included the repetitive use of printed diagnostic and treatment algorithms by professionals. Data on the quantity and class of antibiotic prescribing, which were collected from multiple sources, were measured for the intervention period (from January through June) in 2001 and compared with data for the baseline period during the same months in 2000. RESULTS Medicaid claims data revealed that the percentage of patients in the community who received antibiotics for URTIs during the intervention period was 15.6% less than that for the baseline period, whereas the percentage in the rest of rural Utah was relatively stable, with a 1.5% decrease (P=.006). The greatest impact of the intervention was on prescribing for acute bronchitis (decreases of 56.1% and 1.7% in the community and rural Utah, respectively; P=.024) and on prescribing of macrolides (decreases of 13.4% and 0.2% in the community and rural Utah, respectively; P<.001). Community pharmacy data likewise revealed a 17.5% decrease in the rate of antibiotic prescribing during the intervention period (P<.001), with the largest decrease observed for macrolide prescribing (50.9%; P<.001). Chart review data, in contrast, revealed no significant decrease in the percentage of patients with URTI who were prescribed an antibiotic (3.8%; P=.49), although there was a significant decrease of 11.2% in macrolide use (P=.045). CONCLUSIONS A multifaceted intervention involving the repetitive use of printed algorithms resulted in modest improvements in antibiotic prescribing for outpatient URTIs, although one data source did not corroborate this. However, macrolide prescribing decreased sharply, irrespective of the source of data.

Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension.

We quantified vitamin A in the cerebrospinal fluid of patients with idiopathic intracranial hypertension, elevated intracranial pressure of other causes and normal intracranial pressure. Vitamin A could be detected by high‐pressure liquid chromatography in most of the specimens. There was a significantly higher level of vitamin A in the cerebrospinal fluid of some patients with idiopathic intracranial hypertension. Vitamin A toxicity may play a role in the pathogenesis of idiopathic intracranial hypertension.

Exploring the relationship between chronic undernutrition and asymptomatic malaria in Ghanaian children.

BackgroundA moderate association has been found between asymptomatic parasitaemia and undernutrition. However, additional investigation using the gold standard for asymptomatic parasitaemia confirmation, polymerase chain reaction (PCR), is needed to validate this association. Anthropometric measurements and blood samples from children less than five years of age in a rural Ghanaian community were used to determine if an association exists between chronic undernutrition and PCR-confirmed cases of asymptomatic malaria.MethodsThis was a descriptive cross-sectional study of 214 children less than five years of age from a community near Kumasi, Ghana. Blood samples and anthropometric measurements from these children were collected during physical examinations conducted in January 2007 by partners of the Barekuma Collaborative Community Development Programme.ResultsFindings from the logistic model predicting the odds of asymptomatic malaria indicate that children who experienced mild, moderate or severe stunting were not more likely to have asymptomatic malaria than children who were not stunted. Children experiencing anaemia had an increased likelihood (OR = 4.15; 95% CI: 1.92, 8.98) of asymptomatic malaria. Similarly, increased spleen size, which was measured by ultrasound, was also associated with asymptomatic malaria (OR = 2.17; 95% CI: 1.44, 3.28). Fast breathing, sex of the child, and age of the child were not significantly associated with the asymptomatic malaria.ConclusionsNo significant association between chronic undernutrition and presence of asymptomatic malaria was found. Children who experience anaemia and children who have splenomegaly are more likely to present asymptomatic malaria. Programmes aimed at addressing malaria should continue to include nutritional components, especially components that address anaemia.

Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension.

Background: Several studies have implicated vitamin A-related compounds in the pathogenesis of idiopathic intracranial hypertension (IIH). The goal of this study was to compare cerebrospinal fluid (CSF) and serum concentrations of retinol and retinol-binding protein (RBP) in subjects with and without IIH. Methods: CSF and serum samples were collected from 87 subjects. The study population was composed of subjects with IIH (IIH group, n = 28), subjects with non-IIH neurologic conditions (neurology controls, n = 42), and subjects undergoing preoperative lumbar puncture but with no known neurologic conditions (anesthesia controls, n = 17). RBP levels (nM) were determined using radial immunodiffusion, and retinol levels (nM) were determined using high-performance liquid chromatography. Results: The retinol/RBP ratio was greater in CSF than in serum, especially in subjects with IIH. Conclusions: The finding of increased levels of unbound retinol in the CSF of subjects with IIH provides further evidence that vitamin A may be involved in the pathogenesis of IIH. Comparative statistical analyses revealed multivariate relationships that demonstrate the need to further investigate correlations between vitamin A and RBP levels in CSF and serum.