A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy : study protocol

Abstract Background Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. Methods A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional ‘control’ DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). Discussion Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Outcomes of nasopharyngeal carcinoma screening for high risk family members in Hong Kong

We undertook a large retrospective study to evaluate the impact of screening family members of NPC patients with Epstein Barr Virus (EBV) serology. 1,199 asymptomatic family members of NPC patients were entered into the annual screening program with EBV serology and nasopharyngoscopy between 1994 and 2005. Eighteen participants of our screening program developed NPC;17 of them were treated in our institute, of whom 16 were detected in screening. The sensitivity and specificity of EBV serology were 83.3 and 87.0%, respectively, and for the program they were 88.9 and 87.0%, respectively. Stage distributions and survival outcomes of the 17 cases were compared with that of 1,185 consecutive symptomatic patients diagnosed in the same period through general referral. It was found that the screening program resulted in early detection of cancer, with 59% presenting at early stage (stage I: 41%, stage II: 18%) compared to 24% (stage I:<1%, stage II: 23%) of symptomatic cancers (P<0.001), and a significant improvement in disease-free survival (P = 0.04). The cancer specific survival and overall survival rate at 5-year are also higher (92 vs. 77% and 92 vs. 70%, respectively), though they fail to reach statistical significance. In conclusion, screening asymptomatic family members of NPC patients annually leads to earlier detection of NPC and clinically valuable survival advantage among these family members. A larger sample size is needed to confirm its full potential in survival benefit. ©Springer Science+Business Media B.V. 2009.Link_to_subscribed_fulltex

An analysis of the efficacy of serial screening for familial nasopharyngeal carcinoma based on Markov chain models

Treatment of nasopharyngeal carcinoma (NPC) can be improved by early detection of the disease as treatment outcome worsens with disease's progression. This can be achieved with a mass screening program using Epstein Barr virus (EBV) serology and nasopharyngoscopy. The efficacy of any screening strategy should be evaluated before putting it into practice. Such evaluation is ideally performed with simulation as time and cost often preclude the evaluation by randomized trial. This study simulated and compared the outcomes of 4 screening strategies over a period of 12 years: (A) Annual screening, (B) biennial screening, (C) triennial screening, and (D) triennial screening for participants tested EBV negative and annual screening once the participants are tested EBV positive. Progression of the disease was divided into 4 phases and calculated by applying Markov chain model. Parameters of the transition matrix and probabilities were estimated using data from previous screening results of 1,072 family members of NPC patients. The early detection rates with strategies A, B, C and D are 88, 79, 71 and 87% respectively. The 5-year overall survival with screening is 10-12% higher than that without and is the highest with strategies A and D. Strategy D, however, requires only 64% screening tests compared with strategy A and has almost identical resultant disease stage distribution to strategy A. We concluded that strategy D offered the highest efficacy for NPC screening of family members of NPC patients among the four strategies studied. © 2010 Springer Science+Business Media B.V.Link_to_subscribed_fulltex

Effects of footwear midsole thickness on running biomechanics

Shoe manufacturers launch running shoes with increased (e.g., maximalists) or decreased (e.g., minimalists) midsole thickness and claim that they may prevent running injury. Previous studies tested footwear models with different midsole thicknesses on the market but the shoe construct was not strictly comparable. Therefore, in the present study, we examined the effect of midsole thickness, from 1-mm to 29-mm, in a standard test shoe prototype on the vertical loading rates, footstrike angle and temporal spatial parameters in distance runners. Fifteen male habitual rearfoot strikers were recruited from local running clubs. They were asked to run on an instrumented treadmill in shoes with different midsole thicknesses. We found significant interactions between midsole thickness with vertical loading rates (p < 0.001), footstrike angle (p = 0.013), contact time (p < 0.001), cadence (p = 0.003), and stride length (p = 0.004). Specifically, shoes with thinner midsole (1- and 5-mm) significantly increased the vertical loading rates and shortened the contact time, when compared with thicker midsole shoes (25- and 29-mm). However, we did not observe any substantial differences in the footstrike angle, cadence and stride length between other shod conditions. The present study provides biomechanical data regarding the relationship between full spectrum midsole thicknesses and running biomechanics in a group of rearfoot strikers

Screening for family members of patients with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. Familial aggregation is evident, hence screening for early detection is offered by oncology centers in Hong Kong to first-degree relatives of patients with NPC. During the period 1994-2001, 929 family members were screened in our center. The screenees were advised to attend an annual examination that includes serological test against Epstein Barr Virus (EBV), physical examination to exclude cervical lymphadenopathy and cranial nerve palsy, and endoscopic examination of the nasopharyngeal region. Two different methods were used for the serology test: indirect immune-fluorescent (IF) test for IgA against viral capsid antigen; and starting in 1997 enzyme-linked immunosorbent assay (ELIZA) against nuclear antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were diagnosed, giving a detection rate of 5/1,155 (433/100,000) person-year for male and 7/1,404 (499/100,000) person-year for female participants observed. The corresponding average annual incidence in Hong Kong during this period was 24.1 and 9.6 per 100,000, respectively. Forty-one percent of these detected cases had Stage I disease, whereas only 2% of patients referred to the department for primary treatment presented with such early disease. Six cases were detected at first visit, and all were EBV-positive. Another 78 screenees with positive serology at first visit were followed up for 204 person years, and thus far NPC was detected in 3 after an interval of 6-32 months. Of the 845 initially EBV-negative screenees followed up for 2,337 person-years, NPC was detected in 3 after an interval of 12-45 months. One showed sero-conversion at the time of diagnosis. We conclude that family members of known patients do show a substantially higher risk of developing NPC, and regular screening by current method improves the chance of early detection. © 2004 Wiley-Liss, Inc.Link_to_subscribed_fulltex

Reliability of a Novel Preoperative Protocol for Determining Graft Sizes for Superior Capsular Reconstruction Using Plain Film Radiography

Background: Superior capsular reconstruction (SCR) for massive, irreparable rotator cuff tears involves anchoring a graft between the superior glenoid and the greater tuberosity of the humerus. Optimizing the graft size is important. We aimed (1) to evaluate the reliability of plain film radiography in determining graft size for SCR and (2) to create a database to help predict future graft sizes. Methods: An inter- and intra-rater reliability trial was conducted on 10 and 6 subjects with healthy shoulders, respectively, using plain film radiography to measure the distance between the superior glenoid and the supraspinatus footprint. The subjects were positioned upright with an abduction pillow modified to hold the shoulder at 30° abduction and 45° external rotation, afterwhich a true antero-posterior shoulder radiograph was captured. Thirty subjects were recruited for the database and grouped using the aforementioned protocol. Results: The inter-rater and intra-rater trial agreement was excellent, with intraclass correlation coefficients of 0.94 (95% CI) and 0.76 (95% CI), respectively. Three medio-lateral patch sizes, of 33 mm, 38 mm, and 47 mm, were proposed based on the protocol in 30 subjects. Conclusions: Plain film radiography demonstrated excellent reliability in measuring the distance between the superior glenoid and the supraspinatus footprint. Three ordinal patch sizes are proposed

Influence of midsole thickness on vertical loading rates, footstrike pattern and temporal spatial parameters in runners

Rationale/Objectives: Midsole thickness is a key component in the running shoe design. Increased (e.g. maximalists) or decreased (e.g. minimalists) midsole thickness have been proposed to lower impact loading and prevent running injury. Previous studies tested different shoe models on the market, which may differ in the shoe constructs other than midsole. Therefore, we used identical shoe models with a range of midsole thicknesses (1, 5, 9, 21, 25 and 29 mm) to examine the effect on the loading rates and running kinematics. Methods: Fifteen male habitual rearfoot strikers were asked to run on an instrumented treadmill with six shod conditions in a randomized test sequence. Average and instantaneous loading rates (VALR and VILR), footstrike angle (FSA) and temporal spatial parameters (i.e., contact time, cadence, and stride length) were compared between six shod conditions. Results: Repeated measures ANOVA indicated significant effect on VALR (p<0.001), VILR (p<0.001), footstrike angle (p=0.013), contact time (p<0.001), cadence (p=0.003) and stride length (p=0.004) between the six shod conditions. Pairwise comparisons showed that shoes with thinner midsole (1 and 5 mm) increased vertical loading rates and shortened the contact time, when compared with thicker midsole shoes (25 and 29 mm). Conclusions: Shoes with thinner midsole thickness (< 5 mm) may increase vertical loading rates and reduce contact time. Yet, midsole thickness may not pose a direct influence on footstrike pattern, cadence and stride length