Clinical course, costs and predictive factors for response to treatment in carpal tunnel syndrome: The PALMS study protocol

Background Carpal tunnel syndrome (CTS) is the most common neuropathy of the upper limb and a significant contributor to hand functional impairment and disability. Effective treatment options include conservative and surgical interventions, however it is not possible at present to predict the outcome of treatment. The primary aim of this study is to identify which baseline clinical factors predict a good outcome from conservative treatment (by injection) or surgery in patients diagnosed with carpal tunnel syndrome. Secondary aims are to describe the clinical course and progression of CTS, and to describe and predict the UK cost of CTS to the individual, National Health Service (NHS) and society over a two year period. Methods/Design In this prospective observational cohort study patients presenting with clinical signs and symptoms typical of CTS and in whom the diagnosis is confirmed by nerve conduction studies are invited to participate. Data on putative predictive factors are collected at baseline and follow-up through patient questionnaires and include standardised measures of symptom severity, hand function, psychological and physical health, comorbidity and quality of life. Resource use and cost over the 2 year period such as prescribed medications, NHS and private healthcare contacts are also collected through patient self-report at 6, 12, 18 and 24 months. The primary outcome used to classify treatment success or failures will be a 5-point global assessment of change. Secondary outcomes include changes in clinical symptoms, functioning, psychological health, quality of life and resource use. A multivariable model of factors which predict outcome and cost will be developed. Discussion This prospective cohort study will provide important data on the clinical course and UK costs of CTS over a two-year period and begin to identify predictive factors for treatment success from conservative and surgical interventions

Prostate Cancer Postoperative Nomogram Scores and Obesity

Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28–0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01–1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11–1.90).Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making

VAMP7 modulates ciliary biogenesis in kidney cells

Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis. © 2014 Szalinski et al

Traversing ethical imperatives: Learning from stories from the field

In this chapter we integrate the lessons that are shared across this handbook through the rich, storied examples of ethics in critical research. We outline central themes to the handbook that cut across all of the sections. The notions of vulnerability and harm are pertinent in critical research not only as a duty to protect participants, but also as signifiers that are mobilised and can constrain what is achieved in critical research. The stories told in this handbook contribute to ongoing learning about ethics in critical research by drawing on ethically important moments in the unfolding research processes. We ask whether ethical critical research requires relational models of reciprocity between researchers and participants/co-researchers and appreciation of situated ethics in the bureaucratic review processes

Impact of cardiac transplantation in 24 hours circadian blood pressure and heart rate profile

Objective. The aim of the present study was to evaluate 24 hours blood pressure (BP) and heart rate changes as well as 24-hour circadian BP rhythm of cardiac transplant recipients. Methods. Twenty-five transplant recipients and twenty-five healthy volunteers underwent 24-hour ambulatory BP monitoring. Parameters of 24-hour ambulatory BP monitoring (24-h/daytime/nightime systolic, diastolic BP, pulse pressure, and heart rate) were determined in all patients. Results. Clinic systolic/diastolic BP, mean 24-h systolic/diastolic BP, mean daytime systolic/diastolic BP, mean nighttime systolic/diastolic BP, and mean 24-h/daytime/nighttime heart rate were significantly higher in transplant recipients than in control group subjects. Standard deviations of 24-h/daytime/nighttime heart rates were significantly lower in transplant recipients. Dippers were 48% of the control and only 12% of the transplantation group. Conclusions. Cardiac transplant recipients had increased ambulatory BP. They also had increased 24-h/daytime/nighttime heart rate and decreased heart rate variability. Also, diminished nocturnal decrease of BP was found in transplant recipients

Carotid artery intima-media thickness could predict the presence of coronary artery lesions

The purpose of the present study was to examine whether intima-media thickness (IMT) predicts the presence of the coronary artery lesions independent of other risk factors including clinic blood pressure (BP), parameters of 24-h ambulatory BP monitoring, body mass index, serum cholesterol. and glucose levels. The study population consisted of 390 consecutive subjects who had recently under-one coronary arteriography; 51 subjects with no measurable lesions in their coronary arteries (control group) and 339 subjects with coronary artery lesions (coronary artery disease [CAD] group). Mean IMT of the common carotid artery (MCCA) and internal carotid artery (MICA) were significantly higher in subjects with CAD compare control subjects (P <.0001). Carotid IMT could predict the presence of coronary artery lesions independently of clinic or ambulatory BP values, BMI, serum cholesterol, and glucose levels (P <.01). Carotid IMT predicted the presence of significant coronary artery lesions with cutoff values 0.85 and 0.80 for MICA and MCCA, respectively. The IMT Could be a clinical useful test for the presence of significant coronary artery lesions. (c) 2005 American Journal of Hypertension, Ltd

Development of a low-cost strabismus surgery simulation model

Background/objectives: Strabismus surgery training has historically focussed on the “see one, do one and teach one” approach. Simulation training offers an alternative to practice surgical skills without direct patient involvement. However, current simulation models for strabismus surgery are limited due to concerns regarding use of animal or human tissue and financial cost limiting practice. Our aim was to build and validate a low-cost model for obtaining the core skills required in strabismus surgery. / Subjects/methods: A low-cost strabismus model was developed using commercially available materials. Ophthalmic trainees, fellows and consultants were surveyed using a questionnaire to assess the realism and training utility of the model using a five-point Likert scale (1 = unacceptable, 2 = poor, 3 = acceptable, 4 = favourable and 5 = excellent) whilst simulating a horizontal muscle resection task. / Results: Forty-two ophthalmologists completed the questionnaire. The model scored highly for muscle securing and suturing (median: 4.00) and suturing. Muscle dissection and conjunctiva were considered poor (median: 3.00, 2.50, respectively). Overall, participants felt that the model simulated strabismus surgery well (median: 4.00) and was comparable to other dry simulation models (median: 4.00). / Conclusion: Our study describes a favourable training model that can be used for independent practice of core strabismus surgical techniques. However, it remains a technical challenge to replicate certain ocular anatomy using commercially available materials