Synthesis, Characterization, and Reactivity Studies of para-Substituted Triaryltin Cobaloximes

Several six-coordinate cobaloxime compounds containing a triaryltin ligand were synthesized and characterized. These cobaloximes include (4- t-BuPy)Co(DH)2Sn(C6H4-p -tolyl)3, (4-t-BuPy)Co(DH)2Sn(C 6H4-p-t-Bu)3, (NH3)Co(DH) 2SnPh3, and (4-t-BuPy)Co(DH)2Bn. (4-t-BuPy)Co(DH)2Sn(C6H4- p-tolyl)3 crystallized in the centrosymmetric triclinic space group P-1 (Z=4) with unit cell dimensions a = 13.2949(5) A, b = 17.7508(7) A, c = 18.2240(7) A, alpha = 107.1983(13)°, beta = 91.6597(13)°, gamma = 107.6992(12)°, and Volume = 3880.5(3) A 3. The structure was isostructural with other alkyl cobaloximes. Preliminary X-ray structure analysis determined that (NH3)Co(DH)2SnPh 3 had a NH3 ligand bound to the six-coordinate octahedral cobalt center and trans to the triaryltin ligand. The para-substituted cobaloximes were synthesized through a Gringard reaction to obtain the tetraaryltin species, SnAr4, followed by an adapted Jolly redistribution procedure to obtain the triaryltin chloride species, ClSnAr3. The SnAr 4 compounds synthesized were Sn(C6H4- p-tolyl)4, Sn(C6H4-p-t-Bu) 4, and Sn(C6H4-p-OCH3) 4. The ClSnAr3 complexes synthesized successfully were ClSn(C 6H4-p-tolyl)3 and ClSn(C 6H4-p-t-Bu)3. These ClSnAr 3 complexes were used as the tin ligand to synthesize the corresponding cobaloxime compounds. Once synthesized, the cobaloximes underwent halogen cleavage titrations to investigate the effects of changes in the cobaloxime coordination environment and to compare their reactivity to that of the Co III(OEP)SnPh3. The multiple products formed through these halogen cleavage reactions indicates that the Co-Sn bond is not cleaved cleanly for these cobaloximes, unlike the porphyrins compounds. The cobaloximes react with the halogens to first cleave the Sn-C bonds through electrophilic aromatic substitution, indicating that cleavage of the Sn-C bond is more facile than cleavage of the Co-Sn bond in these compounds

A Benefit of Context Reinstatement to Recognition Memory in Aging: The Role of Familiarity Processes

Reinstatement of encoding context facilitates memory for targets in young and older individuals (e.g., a word studied on a particular background scene is more likely to be remembered later if it is presented on the same rather than a different scene or no scene), yet older adults are typically inferior at recalling and recognizing target–context pairings. This study examined the mechanisms of the context effect in normal aging. Age differences in word recognition by context condition (original, switched, none, new), and the ability to explicitly remember target–context pairings were investigated using word–scene pairs (Experiment 1) and word–word pairs (Experiment 2). Both age groups benefited from context reinstatement in item recognition, although older adults were significantly worse than young adults at identifying original pairings and at discriminating between original and switched pairings. In Experiment 3, participants were given a three-alternative forced-choice recognition task that allowed older individuals to draw upon intact familiarity processes in selecting original pairings. Performance was age equivalent. Findings suggest that heightened familiarity associated with context reinstatement is useful for boosting recognition memory in aging

Anti-glycoprotein VI mediated immune thrombocytopenia: An under-recognized and significant entity?

Idiopathic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by relapsing/remitting thrombocytopenia. Bleeding complications are infrequent with platelet counts above 30x10(9)/L, and this level is commonly used as a threshold for treatment. The question of another/co-existent diagnosis or an alternate mechanism of platelet destruction arises when bleeding is experienced with platelet counts above this threshold. We report a case of anti-GPVI mediated ITP that was diagnosed following investigations performed to address this key clinical question. A patient with ITP experienced exaggerated bruising symptoms despite a platelet count of 91x10(9)/L. Platelet functional testing showed an isolated platelet defect of collagen-induced aggregation. Next generation sequencing excluded a pathogenic variant of GP6, and anti-GPVI antibodies that curtailed GPVI function were confirmed by extended platelet phenotyping. We propose that anti-GPVI mediated ITP may be under-recognized, and that inclusion of GPVI in antibody detection assays may improve their diagnostic utility and in turn, facilitate a better understanding of ITP pathophysiology and aid individualized treatment approaches

The development of a decision aid for tinnitus

OBJECTIVE: To develop a decision aid for tinnitus care that would meet international consensus for decision aid quality. DESIGN: A mixed methods design that included qualitative in-depth interviews, literature review, focus groups, user testing and readability checking. STUDY SAMPLE: Patients and clinicians who have clinical experience of tinnitus. RESULTS: A decision aid for tinnitus care was developed. This incorporates key evidence of efficacy for the most frequently used tinnitus care options, together with information derived from patient priorities when deciding which choice to make. CONCLUSION: The decision aid has potential to enable shared decision making between clinicians and patients in audiology. The decision aid meets consensus standards

Incident vertebral fractures in children with leukemia during the four years following diagnosis

Objectives: The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL). Patients and Methods: Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors. Results:Atotal of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4 -9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m2 increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0 -11.8; P \u3c .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. Conclusions: One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patient\u27s clinical course, including a VF at diagnosis

Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy

Yoga for older adults with multimorbidity (the Gentle Years Yoga Trial): study protocol for a randomised controlled trial

Background: Multimorbidity is common in older adults and associated with high levels of illness burden and healthcare expenditure. The evidence base for how to manage older adults with multimorbidity is weak. Yoga might be a useful intervention because it has the potential to improve health-related quality of life, physical functioning, and several medical conditions. The British Wheel of Yoga’s Gentle Years Yoga© (GYY) programme was developed specifically for older adults, including those with chronic medical conditions. Data from a pilot trial suggested feasibility of using GYY in this population, but its effectiveness and cost-effectiveness remain uncertain. Methods: This is a multi-site, individually randomised, superiority trial with an embedded process evaluation and an economic analysis of cost-effectiveness. The trial will compare an experimental strategy of offering a 12-week GYY programme against a control strategy of no offer in community-dwelling adults aged 65 or over who have multimorbidity, defined as having two or more chronic conditions from a predefined list. The primary outcome is health-related quality of life measured using the EQ-5D-5L, the primary endpoint being the overall difference over 12 months. Both groups will continue to be able to access their usual care from primary, secondary, community, and social services. Participants, care providers, and yoga teachers will not be blinded to the allocated intervention. Outcome measures are primarily self-reported. The analysis will follow intention-to-treat principles. Discussion: This pragmatic randomised controlled trial will demonstrate if the GYY programme is an effective, costeffective, and viable addition to the management of older adults with multimorbidity. Trial registration: ISRCTN ISRCTN13567538. Registered on 18 March 2019 Keywords: Aged, Multimorbidity, Mind-body therapies, Health-related quality of life, Randomised controlled tria

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer