Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

Alcohol, Osteoporosis, and Bone Regulating Hormones

The mechanism of the production of ethanol-associated osteopenia seems to be a direct effect of alcohol on bone cells and an indirect or modulating effect through mineral regulating hormones such as vitamin D metabolites, parathyroid hormone, and calcitonin. The modulating effects of these hormones on bone and mineral metabolism in acute and chronic alcohol consumption is discussed herein. Key Words: Alcohol, PTH, Calcitonin, Vitamin D, Bone.     

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.     

Food allergy as a risk factor for asthma morbidity in adults.

BACKGROUND: The objective of this study was to evaluate the relationship between food allergy and asthma morbidity in adults. METHODS: We interviewed a cohort of persistent asthmatics from an inner-city clinic. Allergies to food were assessed by patient report of convincing symptoms of acute allergic reactions. Outcome variables included health resource utilization and medication use. RESULTS: The prevalence of allergy to fish, peanut, tree-nut, shellfish, and seed allergies were 3%, 3%, 3%, 13%, and 1%. Patients with allergies to > 1 food had increased asthma hospitalizations, ED visits, and use of oral steroids (p < 0.05 for all comparisons). Specifically, allergy to fish was associated with a greater risk of health resource utilization and increased frequency of oral steroid use (p < or = 0.03 for all comparisons). CONCLUSIONS: Self-reported allergy to foods was associated with worse outcomes, suggesting that food allergy may be a risk factor for increased asthma morbidity in adults.     

Allergenicity of orally administered immunoglobulin preparations in food-allergic children

Passive immunization by the oral administration of immunoglobulin preparations derived from bovine milk, chicken egg, and human sera has been proposed as a method for the prevention and treatment of enteric diseases. However, the allergenic potential of these proteins may be a factor limiting their widespread use for disease prevention. An in vitro study with sera from milk- and egg-allergic children was performed to determine whether these immunoglobulin preparations have allergenic potential. Protein extracts of milk, bovine immunoglobulin, egg white, human immune globulin, and five egg yolk antiviral immunoglobulin preparations were bound to nitrocellulose paper. These preparations were probed for specific IgE binding with sera from milk- and egg-allergic patients. Of 22 milk-hypersensitive patients, 16 had specific IgE binding against the bovine immunoglobulin preparation. Of 28 egg-allergic patients 15 had specific IgE binding against one or more of the egg yolk-derived antiviral chicken immunoglobulins. Control sera were negative against the milk and egg preparations. Western blot analysis confirmed that milk- and egg-allergic patients had IgE-specific antibodies for bovine and chicken immunoglobulin molecules. Therefore, the removal of contaminating proteins from milk and egg antibody preparations would be unlikely to eliminate their allergenic potential. In contrast, sera from milk- and egg-allergic patients displayed no detectable IgE binding to human immunoglobulin preparations. These data indicate that the administration of antibody preparations derived from bovine and chicken sources may lead to severe allergic reactions in milk- or egg-sensitized patients and to sensitization in some nonallergic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)