Citations

Classic multinomial logit model, commonly used in multiclass regression problem, is restricted to few predictors and does not take into account the relationship among variables. It has limited use for genomic data, where the number of genomic features far exceeds the sample size. Genomic features such as gene expressions are usually related by an underlying biological network. Efficient use of the network information is important to improve classification performance as well as the biological interpretability. We proposed a multinomial logit model that is capable of addressing both the high dimensionality of predictors and the underlying network information. Group lasso was used to induce model sparsity, and a network-constraint was imposed to induce the smoothness of the coefficients with respect to the underlying network structure. To deal with the non-smoothness of the objective function in optimization, we developed a proximal gradient algorithm for efficient computation. The proposed model was compared to models with no prior structure information in both simulations and a problem of cancer subtype prediction with real TCGA (the cancer genome atlas) gene expression data. The network-constrained mode outperformed the traditional ones in both cases.

SummaryHaemorrhagic complications remain a challenge with surgical procedures in patients with bleeding disorders. In children and young adults, the most commonly performed surgeries are tonsillectomies and/or adenoidectomies. Adequate haemostasis in these patients with bleeding disorders is centred on comprehensive perioperative haemostatic support and dexterous surgical technique. The aim of this study was to assess postoperative bleeding complications with tonsillectomy and/or adenoidectomy in children and young adults with known bleeding disorders. Retrospective review of all patients aged <25 years with known bleeding disorders who underwent tonsillectomy and/or adenoidectomy at Mayo Clinic, Rochester MN between July 1992 and July 2012. In contrast to reported literature, we observed a higher rate of bleeding complications (10/19, 53%) despite aggressive haemostatic support and appropriate surgical techniques. Delayed bleeding (>24 h postoperatively) was more common than early bleeding; and recurrent bleeding was associated with older age. Children and young adults with haemorrhagic diatheses undergoing adenotonsillectomy are at a higher risk of delayed bleeding and require close monitoring with haemostatic support for a prolonged duration in the postoperative period. A uniform approach is needed to manage these patients perioperatively by establishing standard practice guidelines and ultimately reduce postsurgical bleeding complications.

Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process.Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture.Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium.Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium.Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool.

AbstractBackgroundPrucalopride is a high‐affinity 5‐HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health‐related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride.MethodsThis was an integrated analysis of data from three pivotal multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC‐QOL) scores, Patient Assessment of Constipation Symptoms (PAC‐SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment.Key ResultsPatients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC‐SYM scores correlated well with an improvement in PAC‐QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC‐QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point).Conclusions & InferencesImprovements in PAC‐QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL.

Dysphagia is associated with aspiration, pneumonia, and malnutrition, but remains challenging to identify at the bedside. A variety of exam protocols and maneuvers are commonly used, but the efficacy of these maneuvers is highly variable. We conducted a comprehensive search of 7 databases, including MEDLINE, Embase, and Scopus, from each database's earliest inception through June 9, 2014. Studies reporting diagnostic performance of a bedside examination maneuver compared to a reference gold standard (videofluoroscopic swallow study or flexible endoscopic evaluation of swallowing with sensory testing) were included for analysis. From each study, data were abstracted based on the type of diagnostic method and reference standard study population and inclusion/exclusion characteristics, design, and prediction of aspiration. The search strategy identified 38 articles meeting inclusion criteria. Overall, most bedside examinations lacked sufficient sensitivity to be used for screening purposes across all patient populations examined. Individual studies found dysphonia assessments, abnormal pharyngeal sensation assessments, dual axis accelerometry, and 1 description of water swallow testing to be sensitive tools, but none were reported as consistently sensitive. A preponderance of identified studies was in poststroke adults, limiting the generalizability of results. No bedside screening protocol has been shown to provide adequate predictive value for presence of aspiration. Several individual exam maneuvers demonstrated reasonable sensitivity, but reproducibility and consistency of these protocols was not established. More research is needed to design an optimal protocol for dysphagia detection. Journal of Hospital Medicine 2015;10:256–265. © 2015 Society of Hospital Medicine

Objective. To recognize intrathoracic abnormalities, including expansion or rupture of aortic aneurysms, as a source of acute onset vocal fold immobility.Methods. A case report and review of the literature.Results. An 85-year-old female with prior history of an aortic aneurysm presented to a tertiary care facility with sudden onset hoarseness. On laryngoscopy, the left vocal fold was immobile in the paramedian position. A CT scan obtained that day revealed a new, large hematoma surrounding the upper descending aortic stent graft consistent with an acute contained ruptured aortic aneurysm. She was referred to the emergency department for evaluation and treatment by vascular surgery. She was counseled regarding surgical options and ultimately decided not to pursue further treatment. Her vocal fold immobility was subsequently treated via office-based injection medialization two weeks after presentation and again 5 months after the initial injection which dramatically improved her voice. Follow-up CT scan at 8 months demonstrated a reduction of the hematoma. The left vocal cord remains immobile to date.Conclusion. Ortner’s syndrome, or cardiovocal syndrome, is hoarseness secondary to left recurrent laryngeal nerve palsy caused by cardiovascular pathology. It is a rare condition and, while typically presenting gradually, may also present with acute symptomatology.