Citations

ObjectiveThe relationship between Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB) has long been debated. Although PD is primarily considered a motor disorder, cognitive impairment is often present at diagnosis, and only ∼20% of patients remain cognitively intact in the long term. Alpha‐synuclein (SNCA) was first implicated in the pathogenesis of the disease when point mutations and locus multiplications were identified in familial parkinsonism with dementia. In worldwide populations, SNCA genetic variability remains the most reproducible risk factor for idiopathic PD. However, few investigators have looked at SNCA variability in terms of cognitive outcomes.MethodsWe have used targeted high‐throughput sequencing to characterize the 135kb SNCA locus in a large multinational cohort of patients with PD, PDD, and DLB and healthy controls.ResultsAn analysis of 43 tagging single nucleotide polymorphisms across the SNCA locus shows 2 distinct association profiles for symptoms of parkinsonism and/or dementia, respectively, toward the 3′ or the 5′ of the SNCA gene. In addition, we define a specific haplotype in intron 4 that is directly associated with PDD. The PDD risk haplotype has been interrogated at single nucleotide resolution and is uniquely tagged by an expanded TTTCn repeat.InterpretationOur data show that PD, PDD, and DLB, rather than a disease continuum, have distinct genetic etiologies albeit within one genomic locus. Such results may serve as prognostic biomarkers to these disorders, to inform physicians and patients, and to assist in the design and stratification of clinical trials aimed at disease modification. Ann Neurol 2016;79:991–999

Objectives/HypothesisTo present an overview of the barriers to the implementation of clinical practice guidelines (CPGs) in thyroid cancer management and to introduce a computer‐based clinical support system.Data SourcesPubMed.Review Methods: A review of studies on adherence to CPGs was conducted.ResultsAwareness and adoption of CPGs is low in thyroid cancer management. Barriers to implementation include unfamiliarity with the CPGs and financial concerns. Effective interventions to improve adherence are possible, especially when they are readily accessible at the point of care delivery. Computerized clinical support systems show particular promise. The authors introduce the clinical decision making modules (CDMMs) of the Thyroid Cancer Care Collaborative, a thyroid cancer‐specific electronic health record. These computer‐based modules can assist clinicians with implementation of these recommendations in clinical practice.ConclusionComputer‐based support systems can help clinicians understand and adopt the thyroid cancer CPGs. By integrating patient characteristics and guidelines at the point of care delivery, the CDMMs can improve adherence to the guidelines and help clinicians provide high‐quality, evidence‐based, and individualized patient care in the management of differentiated thyroid cancer. Laryngoscope, 126:2640–2645, 2016

SummaryBackgroundReal‐world comparative benefits and risks of infliximab (IFX) and adalimumab (ADA) in patients with ulcerative colitis (UC) are unclear.AimTo evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti‐TNF agents.MethodsUsing an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti‐TNF (IFX, ADA) prescription after a 12‐month period without any anti‐TNF treatment (baseline), and with a minimum 6‐month follow‐up after anti‐TNF initiation. Primary outcome measures were: all‐cause and UC‐related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti‐TNF, and serious infections. We performed 2:1 propensity‐score matched Cox proportional hazard analysis, and inverse probability‐of‐treatment weight (IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC‐related medication.ResultsWe included 1400 new users of anti‐TNF agents (age, 43 ± 15 years; 52% males), from 2006 to 2014. On propensity‐score matched analysis, there was no significant difference in the risk of UC‐related hospitalisation [IFX vs. ADA; adjusted hazard ratio (aHR), 1.04; 95% confidence interval (CI) 0.71–1.51], corticosteroid use (aHR, 0.85; 95% CI, 0.68–1.06) and serious infections (aHR, 0.62; 95% CI, 0.29–1.34) between IFX‐ and ADA‐treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX – as compared to ADA – treated patients (aHR, 0.82; 95% CI, 0.68–0.99). Results were stable on multiple sensitivity analyses.ConclusionsIn a large retrospective cohort of patients with UC who were new users of anti‐TNF agents, IFX‐treated patients may have lower corticosteroid use than ADA‐treated patients, but risk of hospitalisation and serious infections were comparable.

Abstract There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes “Core” items for minimal assessment of tobacco use at initial and follow-up time points, and an “Extension” set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. Clin Cancer Res; 22(8); 1907–13. ©2016 AACR.

Abstract Purpose: Data on laparoscopic totally extraperitoneal inguinal hernia repairs (TEP-IHRs) suggest that approximately 250 operations are needed to gain mastery, but the annual volume required to maintain high-quality outcomes is unknown. Materials and Methods: A retrospective review was performed of every patient undergoing a TEP-IHR at the Mayo Clinic (Rochester, MN) from 1995 to 2011. Analysis focused on the annual volume of 21 staff surgeons and their specific patient outcomes broken up into three groups: Group 1 (G1) ( n = 1 surgeon) performed >30 repairs per year; Group 2 (G2) ( n = 3 surgeons), 15–30 repairs; and Group 3 (G3) ( n = 17), <15 repairs. Results: In total, 1601 patients underwent 2410 TEP-IHRs, with no significant patient demographic differences among groups. Greater annual surgeon volume (G1 > G2 > G3) was associated with improved outcomes as shown by the respective rates for intra- (1%, 2.6%, and 5.6%) and postoperative (13%, 27%, and 36%) complications, need for overnight stay (17%, 23%, and 29%), and hernia recurrence (1%, 4%, and 4.3%) (all P < .05). Surgeons with greater annual operative volumes were more likely to operate on patients with bilateral and recurrent hernias. Surgeons performing at least 15 repairs per year (G1 and G2) showed improvements in quality metrics over time. Conclusions: Annual operative volumes of >30 repairs per year are associated with the highest quality outcomes for TEP-IHR. Operative volumes of at least 15 repairs per year are associated with improvements in quality metrics over time. Mentorship and operative assistance of low-volume TEP-IHR surgeons may be useful in improving patient outcomes.

We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work‐up and management and hope that the present study will facilitate clinical recognition of further cases. © 2016 Wiley Periodicals, Inc.

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.