Foot related impairments and disability in juvenile idiopathic arthritis persist despite modern day treatment paradigms

Background: Foot problems such as synovitis, growth disturbance and deformity are considered common in juvenile idiopathic arthritis (JIA) and have been previously reported in over 90% of cases. The medical management of JIA appears to have improved recently however little is known about the impact of new regimes on localised joints such as in the foot. This pilot study aimed to investigate the prevalence of foot related impairments and disability, and survey the medical and podiatric management of patients in a cohort of UK children with JIA. Methods: This study was a tertiary care based cross-sectional survey. Thirty consecutive JIA patients with a history of foot and ankle arthritis completed the juvenile arthritis foot disability index questionnaire (JAFI) (0-4 for each domain), child health assessment questionnaire (CHAQ) (0-3), and pain visual analogue scale (VAS) (0-100mm). Foot deformity score (0-38), active and limited joint counts (0-77) and walking speed (m/s) were measured also recorded. Foot care provision over the previous 12 months was determined from the medical records in 23/ 30 participants. Results were analysed using simple descriptive statistics and expressed as median (range). Results: Children received biologic agents in 35%, DMARDs in 65%, and 90% of participants had received multiple intra-articular cortico-steroid injections. Median (range) values for foot disease outcomes were JAFI impairment = 1 (0-3), JAFI activity limitation = 1 (0-4) JAFI participation restriction 1 (0-3), CHAQ = 0.38 (0-2), VAS pain = 22 (0-79), foot deformity = 6 (0-20), active joints = 0 (0-7), limited joints (0-31), walking speed = 1.09 (0.84- 1.38). The JAFI scores represent mild foot related impairment and disability. Gait defects, deformity or abnormal foot posture, and/or active foot disease were the main reasons for referral. 43% of children received specialist podiatry care comprising footwear advice, orthotic therapy, and silicone digital appliances together with intrinsic muscle strengthening exercises. Conclusions: Despite DMARD/biologic regimes and specialist podiatry, foot related impairment and disability persists in JIA children. Foot care appears to be in line with current recommendations. Further study is required to determine the long-term consequences of these changes found during childhood in the foot

Unpacking Loss to Follow-Up Among HIV-Infected Women Initiated on Option B+ In Northern Tanzania: A Retrospective Chart Review

Background: In 2014, Tanzania adopted the Option B+ policy for the prevention of mother-to-child transmission of HIV (PMTCT), which stipulates lifelong antiretroviral therapy (ART) for HIV-infected pregnant, postpartum and breastfeeding women, irrespective of CD4 count or WHO clinical staging. Loss to follow-up (LTFU) during pregnancy and the postpartum period may undermine the effectiveness of Option B+. Factors associated with no follow-up (NFU)  care, may differ from those associated with LTFU at later time points. This study aimed to identify factors associated with NFU and LTFU among women who initiate ART under Option B+ in Moshi, Tanzania.   Methods: We conducted a retrospective chart review of patients initiating ART on Option B+ between February 2014 and December 2015 in Moshi Municipality, Tanzania. Multivariable log-binomial regression was used to analyse factors associated with NFU. Kaplan-Meier survival functions were used to estimate time to LTFU. Multivariable Cox proportion hazards regression models were used to evaluate variables associated with time to LTFU.   Results: Among 468 women initiating ART under the option B+ programme, 109 (23.3%) had NFU after the initial appointment. Factors associated with increased risk of NFU were: age < 25 years (adjusted hazard ratio [aRR] 1.7; 95% CI, 1.2 to 2.3), initiating ART at a hospital compared to a lower level health facilities (aRR 2.9; 95% CI, 2.1 to 3.9), and having no treatment supporter (aRR 1.5; 95% CI, 1.1 to 2.1). LTFU was higher in women aged < 25 years (aHR 1.4; 95% CI, 1.1 to 1.9), and in women with no treatment supporter (aHR 1.8; 95% CI, 1.4 to 2.3). In women who returned to the clinic after ART initiation, no factor was significantly associated with LTFU.   Conclusion: The factors associated with NFU (being young, not having a treatment supporter, and being diagnosed at hospitals) reflect a vulnerable and potentially highly mobile population. Additional interventions are needed to support and retain this group at ART initiation on Option B+

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P<0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P<0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P<0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Characterisation of chilean hazelnut (gevuina avellana) tissues : light microscopy and cell wall polysaccharides

By applying several differential staining techniques and light microscopy, the structure and composition of Chilean hazelnut (Gevuina avellana) seeds were analysed. The structure of the G avellana seed is very simple, with a thin, heavily lignified seed coat and two voluminous cotyledons. The embryo food reserves are uniformly distributed over the cotyledon cells. The cell wall polysaccharides were recovered from the alcohol-insoluble residue by mild treatment with warm chlorite solution and sequential extraction with alkali solutions of increasing concentration. FT-IR spectra in the 1200–850 cm-1 region were used together with chemometric techniques to distinguish the hemicellulosic and pectic polysaccharides in the extracts. The most abundant extracts were fractionated by graded precipitation in ethanol. A xyloglucan was identified by 1H and 13C NMR as the major hemicellulosic polysaccharide, with a sugar composition of 4Glc:3.5Xyl:1Gal:0.5Fuc. The hazelnut cell walls are composed of equivalent amounts of pectic polysaccharides, xyloglucans and cellulose.Fundação para a Ciência e Tecnologia (FCT) - PRAXIS XXI/BPD/18824/99. Research Unit 62/94, QOPNA (Aveiro, Portugal). INCO-DC 96-2205 (OLNOCO)

Evaluation of knowledge levels amongst village AIDS committees after undergoing HIV educational sessions: results from a pilot study in rural Tanzania

ABSTRACT: BACKGROUND: Village AIDS committees (VAC) were formed by the Tanzanian government in 2003 to provide HIV education to their communities. However, their potential has not been realised due to their limited knowledge and misconceptions surrounding HIV, which could be addressed through training of VAC members. In an attempt to increase HIV knowledge levels and address common misconceptions amongst the VACs, an HIV curriculum was delivered to members in rural north western Tanzania. METHODS: An evaluation of HIV knowledge was conducted prior to and post-delivery of HIV training sessions, within members of three VACs in Kisesa ward. Quantitative surveys were used with several open-ended questions to identify local misconceptions and evaluate HIV knowledge levels. Short educational training sessions covering HIV transmission, prevention and treatment were conducted, with each VAC using quizzes, role-plays and participatory learning and action tools. Post-training surveys occurred up to seven days after the final training session. RESULTS: Before the training, "good" HIV knowledge was higher amongst men than women (p = 0.041), and among those with previous HIV education (p = 0.002). The trade-centre had a faster turn-over of VAC members, and proximity to the trade-centre was associated with a shorter time on the committee.Training improved HIV knowledge levels with more members achieving a "good" score in the post-training survey compared with the baseline survey (p = < 0.001). The training programme was popular, with 100% of participants requesting further HIV training in the future and 51.7% requesting training at three-monthly intervals. CONCLUSIONS: In this setting, a series of HIV training sessions for VACs demonstrated encouraging results, with increased HIV knowledge levels following short educational sessions. Further work is required to assess the success of VAC members in disseminating this HIV education to their communities, as well as up-scaling this pilot study to other regions in Tanzania with different misconceptions

Eligibility for interventions, co-occurrence and risk factors for unhealthy behaviours in patients consulting for routine primary care: results from the Pre-Empt study

Smoking, excessive drinking, lack of exercise and a poor diet remain key causes of premature morbidity and mortality globally, yet it is not clear what proportion of patients attending for routine primary care are eligible for interventions about these behaviours, the extent to which they co-occur within individuals, and which individuals are at greatest risk for multiple unhealthy behaviours. The aim of the trial was to examine 'intervention eligibility' and co-occurrence of the 'big four' risky health behaviours - lack of exercise, smoking, an unhealthy diet and excessive drinking - in a primary care population. Data were collected from adult patients consulting routinely in general practice across South Wales as part of the Pre-Empt study; a cluster randomised controlled trial. After giving consent, participants completed screening instruments, which included the following to assess eligibility for an intervention based on set thresholds: AUDIT-C (for alcohol), HSI (for smoking), IPAQ (for exercise) and a subset of DINE (for diet). The intervention following screening was based on which combination of risky behaviours the patient had. Descriptive statistics, χ2 tests for association and ordinal regressions were undertaken. Two thousand sixty seven patients were screened: mean age of 48.6 years, 61.9 % female and 42.8 % in a managerial or professional occupation. In terms of numbers of risky behaviours screened eligible for, two was the most common (43.6 %), with diet and exercise (27.2 %) being the most common combination. Insufficient exercise was the most common single risky behaviour (12.0 %). 21.8 % of patients would have been eligible for an intervention for three behaviours and 5.9 % for all four behaviours. Just 4.5 % of patients did not identify any risky behaviours. Women, older age groups and those in managerial or professional occupations were more likely to exhibit all four risky behaviours. Very few patients consulting for routine primary care screen ineligible for interventions about common unhealthy behaviours, and most engage in more than one of the major common unhealthy behaviours. Clinicians should be particularly alert to opportunities to engaging younger, non professional men and those with multi-morbidity about risky health behaviour. ISRCTN22495456. BACKGROUND METHODS RESULTS CONCLUSION TRIAL REGISTRATIO

Marine mammal hotspots across the circumpolar Arctic

Aim: Identify hotspots and areas of high species richness for Arctic marine mammals. Location: Circumpolar Arctic. Methods: A total of 2115 biologging devices were deployed on marine mammals from 13 species in the Arctic from 2005 to 2019. Getis-Ord Gi* hotspots were calculated based on the number of individuals in grid cells for each species and for phyloge-netic groups (nine pinnipeds, three cetaceans, all species) and areas with high spe-cies richness were identified for summer (Jun-Nov), winter (Dec-May) and the entire year. Seasonal habitat differences among species’ hotspots were investigated using Principal Component Analysis. Results: Hotspots and areas with high species richness occurred within the Arctic continental-shelf seas and within the marginal ice zone, particularly in the “Arctic gateways” of the north Atlantic and Pacific oceans. Summer hotspots were generally found further north than winter hotspots, but there were exceptions to this pattern, including bowhead whales in the Greenland-Barents Seas and species with coastal distributions in Svalbard, Norway and East Greenland. Areas with high species rich-ness generally overlapped high-density hotspots. Large regional and seasonal dif-ferences in habitat features of hotspots were found among species but also within species from different regions. Gap analysis (discrepancy between hotspots and IUCN ranges) identified species and regions where more research is required. Main conclusions: This study identified important areas (and habitat types) for Arctic marine mammals using available biotelemetry data. The results herein serve as a benchmark to measure future distributional shifts. Expanded monitoring and teleme-try studies are needed on Arctic species to understand the impacts of climate change and concomitant ecosystem changes (synergistic effects of multiple stressors). While efforts should be made to fill knowledge gaps, including regional gaps and more com-plete sex and age coverage, hotspots identified herein can inform management ef-forts to mitigate the impacts of human activities and ecological changes, including creation of protected areas

RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, γ-Induced Double-Strand Break Ends

Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random “dirty-ended” DSBs created by DNA damaging agents such as ionizing radiation. Here we present a novel system for monitoring early events in the repair of random DSBs, based on our finding that single-strand tails generated by resection at the ends of large molecules in budding yeast decreases mobility during pulsed field gel electrophoresis (PFGE). We utilized this “PFGE-shift” to follow the fate of both ends of linear molecules generated by a single random DSB in circular chromosomes. Within 10 min after γ-irradiation of G2/M arrested WT cells, there is a near-synchronous PFGE-shift of the linearized circular molecules, corresponding to resection of a few hundred bases. Resection at the radiation-induced DSBs continues so that by the time of significant repair of DSBs at 1 hr there is about 1–2 kb resection per DSB end. The PFGE-shift is comparable in WT and recombination-defective rad52 and rad51 strains but somewhat delayed in exo1 mutants. However, in rad50 and mre11 null mutants the initiation and generation of resected ends at radiation-induced DSB ends is greatly reduced in G2/M. Thus, the Rad50/Mre11/Xrs2 complex is responsible for rapid processing of most damaged ends into substrates that subsequently undergo recombinational repair. A similar requirement was found for RAD50 in asynchronously growing cells. Among the few molecules exhibiting shift in the rad50 mutant, the residual resection is consistent with resection at only one of the DSB ends. Surprisingly, within 1 hr after irradiation, double-length linear molecules are detected in the WT and rad50, but not in rad52, strains that are likely due to crossovers that are largely resection- and RAD50-independent

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

Contains fulltext : 65628.pdf ( ) (Open Access)BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217