Citations

Introduction: Collaborative care management (CCM) for the treatment of depression has been shown to be an effective therapy. CCM can be seen as a resource intensive treatment. Early identification of patients who would not be effectively treated with CCM could allow for alteration of therapy or change in modality. Methods: A retrospective case-controlled study used 132 patients with prolonged enrollment (>1 year) in CCM (cases) and 396 randomized CCM patients who achieved remission within 6 months (controls). The hypothesis was that by studying the epidemiology of patients in prolonged care management (PCM), characteristics could be determined to help define this group. Results: With regression modeling, the odds of a patient having PCM at 1 year was highly significant for those unmarried patients (odds ratio [OR] = 1.736, confidence interval [CI] = 1.115-2.703, P = .015) with dysthymia (OR = 2.362, CI = 1.104-5.052, P = .027) and severe depression (OR = 2.856, CI = 1.551-5.260, P = .001). The adjusted baseline Patient Health Questionnaire–9 (PHQ-9) score showed a difference of 16.0 for the cases versus 14.8 for the controls ( P < .001). By 10 weeks, the difference is much larger at (10.7 vs 4.9, P < .001). At 26 weeks, the control group had an adjusted average PHQ-9 score of 2.0, whereas the case group was still elevated at 10.2 ( P < .001). Conclusions: Case-controlled analysis of PCM patients demonstrated independent predictors (such as unmarried status, diagnosis of dysthymia or severe depression), however, no baseline data was of sufficient clarity to suggest changes in clinical practice. The trend of the patient’s PHQ-9 over time was strongly suggestive of allowing differentiation between the groups.

BackgroundPrevalence and risk factors for focal hemosiderin deposits are important considerations when planning amyloid‐modifying trials for treatment and prevention of Alzheimer's disease (AD).MethodsSubjects were cognitively normal (n = 171), early‐mild cognitive impairment (MCI) (n = 240), late‐MCI (n = 111), and AD (n = 40) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Microhemorrhages and superficial siderosis were assessed at baseline and on all available MRIs at 3, 6, and 12 months. β‐amyloid load was assessed with 18F‐florbetapir positron emission tomography.ResultsPrevalence of superficial siderosis was 1% and prevalence of microhemorrhages was 25% increasing with age (P < .001) and β‐amyloid load (P < .001). Topographic densities of microhemorrhages were highest in the occipital lobes and lowest in the deep/infratentorial regions. A greater number of microhemorrhages at baseline was associated with a greater annualized rate of additional microhemorrhages by last follow‐up (rank correlation = 0.49; P < .001).ConclusionsFocal hemosiderin deposits are relatively common in the ADNI cohort and are associated with β‐amyloid load.

Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the “signature injury” in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo , and how this may be a particularly promising approach to improving functional outcome in patients with TBI.

Purpose In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non–cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease–free survival, incidence of contralateral new primary breast cancer, and safety. Results In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease–free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. Conclusion This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor–positive breast cancer.

Background Cam-type femoral impingement is caused by structural abnormalities of the hip and is recognized as a cause of degenerative hip arthritis. Identifiable etiologies of this structural abnormality include congenital malformation, pediatric hip disease, and malunion of femoral neck fractures after internal fixation. Purpose The purpose of this study was to determine the prevalence of radiographic impingement in healed Orthopaedic Trauma Association (OTA) type 31B fractures treated with reduction and internal fixation. Methods Seventy OTA 31B hip fractures treated with internal fixation were identified from our institutional trauma database and radiographs were retrospectively reviewed for signs of impingement. Mean follow-up was 53 months after fracture. Alpha angle, Mose templates, and femoral head retroversion were the measurements used to determine impingement. Results The overall prevalence of any sign of radiographic impingement was 75%. Alpha angle was elevated in 32 hips (46%), asphericity was present in 46 femoral heads (65%), and femoral head retroversion was present in 26 hips (37%). The rates were highest in displaced subcapital fractures (OTA 31B-3) with a 63% (13/19) prevalence of elevated alpha angle, 68% (14/19) prevalence of asphericity, and 47% (10/19) prevalence of retroversion. Conclusions Prevalence of radiographic signs of impingement in this population is higher than expected based on population-based controls. Surgeons must be vigilant about reduction and fixation of femoral neck fractures. Malunion should be recognized as early intervention may be beneficial in improving long-term outcomes.

Objectives/HypothesisTo describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis.Study DesignRetrospective chart review and systematic review of the literature.MethodsVestibular schwannoma confined to or arising from the inner ear were included. PIES classification was based on anatomic subsite(s) involved. Detailed clinical history and outcomes were recorded.ResultsIn a systematic review (1933–2011), including 14 patients from the authors' institution (1999–2009), a total of 72 studies comprising 234 patients were evaluated. Mean follow‐up was 32.8 ± 39.1 months (range, 0–183 months). The cochlea was the most commonly involved subsite (51%). Hearing loss was the most frequent presenting symptom (99%). Vertigo and abnormal balance were more common among tumors involving the vestibular system (P < .01). Average delay between symptom onset and diagnosis was 7.0 ± 8.0 years (median, 5 years; range, 0–40 years). Recent onset hearing loss was more likely to elicit an earlier diagnosis (P = .01). The majority of patients were observed without treatment (53%). Tumor progression was seen in 52% of patients.Conclusions PIES are rare tumors and most commonly involve the cochlea. Tumor location is often associated with clinical presentation and correlates with delay between symptom onset and diagnosis. A watch‐and‐scan approach is the management strategy of choice in the absence of intractable vertigo or extensive tumor growth. The majority of patients report stable or improved symptoms over time, regardless of treatment. Laryngoscope, 123:1957–1966, 2013

ABSTRACT Adenovirus serotype 5 (Ad5) naturally infects the liver after intravenous injection, making it a candidate for hepatocyte-directed gene transfer. While Ad5 can be efficient, most of the dose is destroyed by liver Kupffer cells before it can reach hepatocytes. In contrast, Ad5 bearing the hexon from Ad6 (Ad5/6) evades Kupffer cells. While Ad5/6 dramatically increases hepatocyte transduction in BALB/c mice, it has surprisingly little effect on C57BL/6 mice. To determine the source of this strain-specific difference, the roles of Kupffer cells, liver sinusoidal endothelial cells (LSECs), hepatocytes, scavenger receptors, clotting factors, and immunoglobulins were analyzed. The numbers of Kupffer cells and LSECs, the level of clotting factor X, and hepatocyte infectibility did not differ between different strains of mice. In contrast, high levels of immunoglobulins correlated negatively with Ad5 liver transduction in different mouse strains. Removal of immunoglobulins by use of Rag-deficient mice restored Ad5 transduction to maximal levels. Removal of Kupffer cells by predosing or by testing in colony-stimulating factor knockout mice restored Ad5 transduction in the presence of immunoglobulins. Partial reconstitution of IgM in Rag mice resulted in significant reductions in liver transduction by Ad5 but not by Ad5/6. These data suggest a role for IgM-mediated clearance of Ad5 via Kupffer cells and may explain the mechanism by which Ad5/6 evades these cells. These mechanisms may play a vital role in Ad pharmacology in animals and in humans.

Background: Polypharmacy has been identified as a quality indicator, but no studies have been reported about the epidemiology of polypharmacy among hospital patients at discharge. Methods: Records of 142 family medicine patients aged ≥65 years who were discharged from the hospital during the period November 2008 to October 2009 were extracted. Forty-six of these patients were readmitted within 30 days and the remaining 96 not readmitted within 30 days. Polypharmacy was measured as >16 medications at dismissal. Independent variables related to person (use of medical care in the 12 months prior to hospitalization, number of high-risk diagnoses, and demographic characteristics), place (living situation at admission and disposition location), and time (month of admission). Chronic obstructive pulmonary disease, cancer, diabetes mellitus, congestive heart failure, and coronary artery disease were diagnoses determined to be high-risk. Results: Mean number of medications at dismissal was 13.5 and 23.2% of patients were prescribed more than 16 medications. No interactions were found between readmission status and any of the independent variables. Use of medical services in the previous year was not related to polypharmacy and no seasonal pattern was detected. Two or more high-risk diagnoses were independently related to polypharmacy (odds ratio [OR] = 4.75, confidence interval [CI] = 1.0-11.2, P = .00). Being discharged to a location with personal health services such as home care or a skilled nursing facility was also related to polypharmacy (OR = 3.07, CI = 1.3-7.2, P = .01). Conclusion: Drug reviews intended to reduce the rate of polypharmacy among discharged persons aged ≥65 years can be targeted at patients who have 2 or more high-risk diagnoses and at those discharged to receive personal health services either at home or in a convalescence facility.