Determination of Glycerol as a Product of Glucose Metabolism in the Intestinal Epithelium of the Roundworm, Ascaris Suum

Physiological Science

The International Guidelines on Natural and Nature Based Features for Fluvial Flood Risk Management:the concept and the way forward

The International Guidelines on Natural and Nature-Based Features for Flood Risk Management emphasize the role of nature-based solutions and natural infrastructure (e.g., beaches, dunes, islands, marshes) as an alternative to conventional hardened infrastructure for flood and coastal storm risk reduction. The Guidelines will equip decision-makers, project planners and practitioners with strategies that reduce flood risks to communities and improve infrastructure resilience. The document is organized so readers can begin where their interests lie. The Guidelines are an excellent starting point for the implementation of NNBF, but there is also a need to develop appropriate frameworks that quantify the (co-)benefits of NNBF. Furthermore, there are opportunities to connect NNBF to global initiatives like the UN Sustainable Development Goals, which even increases the potential of NNBF.</p

Adhesive Capsulitis in Eight Dogs: Diagnosis and Management

ABSTRACT:Objective: To describe clinical and diagnostic findings as well as management of adhesive capsulitis in dogs.Background: Adhesive capsulitis, also known as frozen shoulder, is a syndrome defined by loss of range of motion of the shoulder and may be the end-stage manifestation of several primary conditions.Evidentiary Value: This is a case report series of eight dogs with chronic forelimb lameness diagnosed with adhesive capsulitis.Methods: Medical records (June 1, 2010 to September 1, 2015) including, physical examination findings, radiographic findings, magnetic resonance imaging findings, arthroscopy findings, and treatment plans were reviewed. Results: All dogs presented with a chronic, grade III-VI/VI forelimb lameness. On orthopedic examination all dogs had moderate to significant discomfort on shoulder extension and flexion and severe restriction of range of motion. Six of the eight dogs had evidence of bone remodeling and sclerosis in the affected shoulder on radiographs. Six of had an initial diagnostic ultrasound performed, which revealed evidence of fibrous scar tissue. Five dogs had magnetic resonance imaging performed that revealed moderate shoulder effusion and enhancement of the synovial lining of the shoulder. Arthroscopy was performed in five of the eight patients. Three were noted to have significant contracture, adhesions and fibrous scar tissue of the joint capsule. Severe inflammation was noted throughout the synovium of two patients. All eight patients tried conservative management consisting of oral medications and rehabilitation therapy. Five of the eight patients received extracorporeal shockwave therapy. Three patients received regenerative medicine treatment in the affected supraspinatus and shoulder. Regardless of the treatment elected, none of the dogs were reported to have significant improvement. Conclusion: Adhesive capsulitis is an uncommon cause of chronic forelimb lameness. Further investigation is needed to describe the etiology and pathogenesis of adhesive capsulitis in dogs to evaluate the effectiveness of both non-surgical and surgical treatment modalities, establish treatment protocols, and evaluate short- and long-term clinical outcome of patients.Application: Adhesive capsulitis should be considered in patients with chronic forelimb lameness and moderate to significant discomfort and restriction on shoulder range of motion

Study protocol for a randomised controlled trial of insulin delivery by continuous subcutaneous infusion compared to multiple daily injections

BACKGROUND: Intensive insulin therapy with continuous subcutaneous insulin infusion (CSII) devices or multiple daily injections (MDI) reduces the risk of long-term vascular complications of type I diabetes (TID). Both treatments are used routinely, but there is little evidence to demonstrate superiority of either treatment. If CSII treatment reduces the risk of long-term complications or is associated with an improved quality of life (QoL), the additional cost of this therapy may be compensated for by a reduction in long-term health expenditure. If there is no demonstrable difference between treatments, health-care resources may be better invested elsewhere. This study aims to address this gap in knowledge. METHODS/DESIGN: This is a pragmatic, randomised controlled trial (RCT). Fifteen centres, selected to represent a population with a broad demographic, will recruit 316 patients, newly diagnosed with TID, aged between 7 months and 15 years. Exclusion criteria include additional pathologies or treatments likely to affect glycaemic control and a first-degree relative with TID. Randomisation to CSII or MDI is stratified for age, gender and recruiting centre. The randomised treatment starts within 15 days of diagnosis. Patients will be trained to adjust their insulin dose according to carbohydrate intake and blood glucose level. Study visits coincide with routine clinic appointments at 3, 6, 9 and 12 months when data relating to routine clinical assessments, adverse events and concomitant medications are collected. Health utilities questionnaires are completed at each visit and a diabetes-specific QoL questionnaire (PedsQL) at diagnosis, 6 and 12 months. The primary outcome is glycaemic control (HbA1c) at 12 months. Secondary outcome measures include QoL, insulin use, growth and weight gain, adverse events and a health economics appraisal. DISCUSSION: This is the first adequately powered RCT comparing CSII and MDI in a non-selected population, treated according to standard practice guidelines. It will produce data that are meaningful to individual patients and local and national policymakers. TRIAL REGISTRATION: The study was registered with the European Clinical Trials Database on 4 November 2010, reference 2010-023792-25

Assessing and investigating children with suspected bone and abdominal tumours: an e-Delphi consensus process

Background The incidence of childhood cancer has risen by 15% since the 1990s. Early diagnosis is key to optimising outcomes, however diagnostic delays are widely reported. Presenting symptoms are often non-specific causing a diagnostic dilemma for clinicians. This Delphi consensus process was conducted to develop a new clinical guideline for children and young people presenting with signs/symptoms suggestive of a bone or abdominal tumour. Methods Invitation emails were sent to primary and secondary healthcare professionals to join the Delphi panel. 65 statements were derived from evidence review by a multidisciplinary team. Participants were asked to rank their level of agreement with each statement on a 9-point Likert scale (1=strongly disagree, 9=strongly agree), with responses ≥7 taken to indicate agreement. Statements not reaching consensus were rewritten and reissued in a subsequent round. Results All statements achieved consensus after two rounds. 96/133 (72%) participants responded to round 1 (R1) and 69/96 (72%) completed round 2 (R2). 62/65 (94%) statements achieved consensus in R1 with 29/65 (47%) gaining more than 90% consensus. Three statements did not reach consensus scoring between 61% and 69%. All reached numerical consensus at the end of R2. Strong consensus was reached on best practice of conducting the consultation, acknowledging parental instinct and obtaining telephone advice from a paediatrician to decide the timing and place of review, rather than adult cancer urgent referral pathways. Dissensus in statements was due to unachievable targets within primary care and valid concerns over a potential overinvestigation of abdominal pain

The Childhood Cancer Diagnosis (CCD) Study: a UK observational study to describe referral pathways and quantify diagnostic intervals in children and young people with cancer

Introduction: Childhood cancer is diagnosed in 400 000 children and young people (CYP) aged 0–19 years worldwide annually. In the UK, a child’s cumulative cancer risk increases from 1 in 4690 from birth to aged 1, to 1 in 470 by age 15. Once diagnosed, access to treatments offers survival to adulthood for over 80%. Tumour diagnoses are at a later stage and mortality is higher when compared with those in other parts of Europe. This means higher risk, more intensive therapies for a cure. Some CYPs are known to experience delays to diagnosis which may further contribute to poor outcomes. This study aims to understand the current pathway of childhood cancer referrals and diagnosis and quantify diagnostic intervals in the UK.Methods and analysis: This is a prospective multicentre observational study including all tertiary childhood cancer treatment centres in the UK. CYP (0–18 years) with a new diagnosis of cancer over the study period will be invited to participate. Data will be collected at initial diagnosis and 5 years after diagnosis. Data will include demographic details, clinical symptoms, tumour location, stage and clinical risk group. In addition, key diagnostic dates and referral routes will be collected to calculate the diagnostic intervals. At 5 years’ follow-up, data will be collected on refractory disease, relapse and 1-year and 5-year survival. Population characteristics will be presented with descriptive analyses with further analyses stratified by age, geographical region and cancer type. Associations between diagnostic intervals/delay and risk factors will be explored using multiple regression and logistic regression.Ethics: The study has favourable opinion from the York and Humber, Leeds West REC (19/YH/0416).Dissemination: Results will be presented at academic conferences, published in peer-reviewed journals and disseminated through public messaging in collaboration with our charity partners through a national awareness campaign (ChildCancerSmart).Study registration: researchregistry.com (researchregistry5313)

Adapting Medical Guidelines to Be Patient-centered Using a Patient-driven Process for Individuals With Sickle Cell Disease and Their Caregivers

Background: Evidence-based guidelines for sickle cell disease (SCD) health maintenance and management have been developed for primary health care providers, but not for individuals with SCD. To improve the quality of care delivered to individuals with SCD and their caregivers, the main purposes of this study were to: (1) understand the desire for patient-centered guidelines among the SCD community; and (2) adapt guideline material to be patient-centered using community-engagement strategies involving health care providers, community -based organizations, and individuals with the disease. Methods: From May–December 2016, a volunteer sample of 107 individuals with SCD and their caregivers gave feedback at community forums (n = 64) and community listening sessions (n = 43) about technology use for health information and desire for SCD-related guidelines. A team of community research partners consisting of community stakeholders, individuals living with SCD, and providers and researchers (experts) in SCD at nine institutions adapted guidelines to be patient-centered based on the following criteria: (1) understandable, (2) actionable, and (3) useful. Results: In community forums (n = 64), almost all participants (91%) wanted direct access to the content of the guidelines. Participants wanted guidelines in more than one format including paper (73%) and mobile devices (79%). Guidelines were adapted to be patient-centered. After multiple iterations of feedback, 100% of participants said the guidelines were understandable, most (88%) said they were actionable, and everyone (100%) would use these adapted guidelines to discuss their medical care with their health care providers. Conclusions: Individuals with SCD and their caregivers want access to guidelines through multiple channels, including technology. Guidelines written for health care providers can be adapted to be patient-centered using Community-engaged research involving providers and patients. These patient-centered guidelines provide a framework for patients to discuss their medical care with their health care providers

Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis

Childhood bone tumours in primary care: helping GPs to identify ‘the needle in the haystack’

In 2018, the World Health Organization declared childhood cancer as a global disease burden, launching a Global Initiative to improve survival to 60% worldwide by 2030. If achieved, it is estimated that an extra 1 million children’s lives will be saved. In the UK, childhood cancer is the largest illness cause of death in childhood in 1–19-year-olds and the incidence continues to rise. Unlike in adult cancers, there are no modifiable risk factors or cost-effective screening options and so early diagnosis is key to reducing morbidity, mortality, and late effects from treatment burden