Development and initial validation of a sensory threshold examination protocol (STEP) for phenotyping canine pain syndromes

Objective To study feasibility and test-retest repeatability of a sensory threshold examination protocol (STEP) and report quantitative sensory threshold distributions in healthy dogs. Study design Prospective, observational, cohort study. Animals Twenty-five healthy client-owned dogs. Methods Tactile sensitivity (TST) (von Frey filaments), mechanical thresholds (MT with 2, 4 and 8 mm probes), heat thresholds (HT) and responsiveness to cold stimulus (CT at 0 °C) were quantitatively assessed for five body areas (BA: tibias, humeri, neck, thoracolumbar region and abdomen) in a randomized order on three different occasions. Linear Mixed Model and Generalised Linear Mixed models were used to evaluate the effects of body weight category, age, sex, BA, occasion, feasibility score and investigator experience. Test-retest repeatability was evaluated with the Intra-class Correlation Coefficient (ICC). Results The STEP lasted 90 minutes without side effects. The BA affected most tests (p = 0.001). Higher thresholds and longer cold latencies were scored in the neck (p = 0.024) compared to other BAs. Weight category affected all thresholds (p = 0.037). Small dogs had lower MT (~1.4 N mean difference) and HT (1.1 0C mean difference) than other dogs (p = 0.029). Young dogs had higher HT than adults (2.2 0C mean difference) (p = 0.035). Gender also affected TST, MT and HT (p < 0.05) (females versus males: TST OR= 0.5, MT= 1.3 N mean difference, HT= 2.2 0C mean difference). Repeatability was substantial to moderate for all tests, but poor for TST. There was no difference in thresholds between occasions, except for CT. Test-retest repeatability was slightly better with the 2 mm MT probe compared to other diameters and improved with operator experience. Conclusions and clinical relevance The STEP was feasible, well tolerated and showed substantial test-retest repeatability in healthy dogs. Further validation is needed in dogs suffering pain

Male patients commencing FOLFOX / FOLFIRI chemotherapy in 2014, descriptive statistics

Background: Metastatic colorectal cancer is an incurable illness; however the advent of chemotherapy has significantly improved survival and symptom control. FOLFOX and FOLFIRI are used at SPBOH as the standard of care for patients with metastatic disease. No statistical data is available on that cohort of patients; this study aims to establish a population data-set for patients on FOLFOX/FOLFIRI. Methods: This retrospective cross-sectional study included all patients on FOLFOX and FOLFIRI in 2014. Only male patients were included, data was retrospectively extracted from the ward’s logbook and ISOFT clinical manager. Cycle 1, 6 and 12 dates were documented. Data was analysed using clinically reliable statistical tools, all reported p-values were statistically significant at <0.05. Results: From a total of 108 patients, 4 patients were excluded from the analysis. The average age of patients was 65.2 years. The average length of 12 cycles was 24.5 weeks. 19% of patients had cycles longer than 7 months whereas only 10% lasted more than 8 months on treatment. 41% of patients dropped out before completing the full course with a complication and mortality rate of 17%. Patients on FOLFIRI were more likely to have their chemotherapy changed and were also more likely to have received previous treatment. Conclusion: Although chemotherapy increases survival in metastatic colorectal cancer we have to appreciate that many patients do not proceed smoothly with their treatment. Many of those patients are middle aged independent individuals, after-all the physician must draw the line at the appropriate time and focus on palliative care rather than continuing ineffectively with chemotherapy.peer-reviewe

Molecular evidence of Plasmodium vivax infection in Duffy negative symptomatic individuals from Dschang, West Cameroon

Background: Plasmodium vivax infection is known to be rare in West/Central Africa, the most accepted explanation being the lack of expression of erythroid Duffy antigen in the local human populations. Duffy negativity prevents the parasite to exploit the entry mechanism on the red blood cell surface. However, there are a growing number of reported vivax infections in Duffy-negative individuals. Data on P. vivax circulation in Cameroon are limited. The aim of the study was to evaluate the P. vivax presence, and its association with the Duffy genotype in West Cameroon. Results: Overall, 484 blood samples were collected consecutively from febrile outpatients attending the Dschang’s Hospital (West Cameroon) during a 3-months period. Plasmodium vivax infection was detected by PCR in 5.6% (n = 27/484) of the cases, representing 38.6% (n = 27/70) of all Plasmodium infections detected. All P. vivax infected individuals showed a Duffy-negative genotype, and the frequency of Duffy-positive individuals in the whole tested population was 1.7%. Conclusions: The results of this study confirm the circulation of P. vivax in Cameroon, as well as that the lack of expression of Duffy-antigen does not confer full protection against vivax malaria acquisition

Characterizing fruit ripening in plantain and Cavendish bananas: A proteomics approach

The fruit physiology of banana cultivars other than Cavendish is poorly understood. To study the ripening process, samples were taken daily from plantain and Cavendish bananas and the ripening stages were determined. We present data from the green to the fully mature stage. By analyzing the protein abundances during ripening we provide some new insights into the ripening process and how plantains fruits are different. Multivariate analysis of the proteins was performed correlated to the starch dynamics. A drop in sucrose synthase and a rise of acid invertase during ripening indicated a change in the balance of the sucrose fate. During ripening, sugars may no longer be available for respiration since they are stored in the vacuoles, making citrate the preferred respiratory substrate. We found significant cultivar specific differences in granule-bound starch synthase, alpha- and beta amylases and cell wall invertase when comparing the protein content at the same ripening stage. This corroborates the difference in starch content/structure between both banana types. Differences in small heat shock proteins and in the cell wall-modifying enzyme xyloglucan endotransglucosylase/hydrolase support respectively the presumed higher carotenoid content and the firmer fruit structure of plantains

Post-treatment FDG PET-CT in head and neck carcinoma: comparative analysis of 4 qualitative interpretative criteria in a large patient cohort

There is no consensus regarding optimal interpretative criteria (IC) for Fluorine-18 fluorodeoxyglucose (FDG) Positron Emission Tomography – Computed Tomography (PET-CT) response assessment following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). The aim was to compare accuracy of IC (NI-RADS, Porceddu, Hopkins, Deauville) for predicting loco-regional control and progression free survival (PFS). All patients with histologically confirmed HNSCC treated at a specialist cancer centre with curative-intent non-surgical treatment who underwent baseline and response assessment FDG PET-CT between August 2008 and May 2017 were included. Metabolic response was assessed using 4 different IC harmonised into 4-point scales (complete response, indeterminate, partial response, progressive disease). IC performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy) were compared. Kaplan-Meier and Cox proportional hazards regression analyses were performed for survival analysis. 562 patients were included (397 oropharynx, 53 hypopharynx, 48 larynx, 64 other/unknown primary). 420 patients (75%) received CRT and 142 (25%) had radiotherapy alone. Median follow-up was 26 months (range 3–148). 156 patients (28%) progressed during follow-up. All IC were accurate for prediction of primary tumour (mean NPV 85.0% (84.6–85.3), PPV 85.0% (82.5–92.3), accuracy 84.9% (84.2–86.0)) and nodal outcome (mean NPV 85.6% (84.1–86.6), PPV 94.7% (93.8–95.1), accuracy 86.8% (85.6–88.0)). Number of indeterminate scores for NI-RADS, Porceddu, Deauville and Hopkins were 91, 25, 20, 13 and 55, 70, 18 and 3 for primary tumour and nodes respectively. PPV was significantly reduced for indeterminate uptake across all IC (mean PPV primary tumour 36%, nodes 48%). Survival analyses showed significant differences in PFS between response categories classified by each of the four IC (p <0.001). All four IC have similar diagnostic performance characteristics although Porceddu and Deauville scores offered the best trade off of minimising indeterminate outcomes whilst maintaining a high NPV

Estimating Negative Likelihood Ratio Confidence When Test Sensitivity is 100%: A Bootstrapping Approach

Objectives: Assessing high-sensitivity tests for mortal illness is crucial in emergency and critical care medicine. Estimating the 95% confidence interval (CI) of the likelihood ratio (LR) can be challenging when sample sensitivity is 100%. We aimed to develop, compare, and automate a bootstrapping method to estimate the negative LR CI when sample sensitivity is 100%. Methods: The lowest population sensitivity that is most likely to yield sample sensitivity 100% is located using the binomial distribution. Random binomial samples generated using this population sensitivity are then used in the LR bootstrap. A free R program, “bootLR,” automates the process. Extensive simulations were performed to determine how often the LR bootstrap and comparator method 95% CIs cover the true population negative LR value. Finally, the 95% CI was compared for theoretical sample sizes and sensitivities approaching and including 100% using: (1) a technique of individual extremes, (2) SAS software based on the technique of Gart and Nam, (3) the Score CI (as implemented in the StatXact, SAS, and R PropCI package), and (4) the bootstrapping technique. Results: The bootstrapping approach demonstrates appropriate coverage of the nominal 95% CI over a spectrum of populations and sample sizes. Considering a study of sample size 200 with 100 patients with disease, and specificity 60%, the lowest population sensitivity with median sample sensitivity 100% is 99.31%. When all 100 patients with disease test positive, the negative LR 95% CIs are: individual extremes technique (0,0.073), StatXact (0,0.064), SAS Score method (0,0.057), R PropCI (0,0.062), and bootstrap (0,0.048). Similar trends were observed for other sample sizes. Conclusions: When study samples demonstrate 100% sensitivity, available methods may yield inappropriately wide negative LR CIs. An alternative bootstrapping approach and accompanying free open-source R package were developed to yield realistic estimates easily. This methodology and implementation are applicable to other binomial proportions with homogeneous responses

Gender-specific clinical risk scores incorporating blood pressure variability for predicting incident dementia

Introduction: The present study examined the gender-specific prognostic value of blood pressure (BP) and its variability in the prediction of dementia risk and developed a score system for risk stratification. Materials and Methods This was a retrospective, observational population-based cohort study of patients admitted to government-funded family medicine clinics in Hong Kong between January 1, 2000 and March 31, 2002 with at least 3 blood pressure measurements. Gender-specific risk scores for dementia were developed and tested. Results The study consisted of 74 855 patients, of whom 3550 patients (incidence rate: 4.74%) developed dementia over a median follow-up of 112 months (IQR= [59.8–168]). Nonlinear associations between diastolic/systolic BP measurements and the time to dementia presentation were identified. Gender-specific dichotomized clinical scores were developed for males (age, hypertension, diastolic and systolic BP and their measures of variability) and females (age, prior cardiovascular, respiratory, gastrointestinal diseases, diabetes mellitus, hypertension, stroke, mean corpuscular volume, monocyte, neutrophil, urea, creatinine, diastolic and systolic BP and their measures of variability). They showed high predictive strengths for both male (hazard ratio [HR]: 12.83, 95% confidence interval [CI]: 11.15–14.33, P value &amp;lt; .0001) and female patients (HR: 26.56, 95% CI: 14.44–32.86, P value &amp;lt; .0001). The constructed gender-specific scores outperformed the simplified systems without considering BP variability (C-statistic: 0.91 vs 0.82), demonstrating the importance of BP variability in dementia development. Conclusion Gender-specific clinical risk scores incorporating BP variability can accurately predict incident dementia and can be applied clinically for early disease detection and optimized patient management