Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Baby-Led Weaning: The Evidence to Date

Purpose of ReviewInfants are traditionally introduced to solid foods using spoon-feeding of specially prepared infant foods.Recent FindingsHowever, over the last 10–15 years, an alternative approach termed ‘baby-led weaning’ has grown in popularity. This approach involves allowing infants to self-feed family foods, encouraging the infant to set the pace and intake of the meal. Proponents of the approach believe it promotes healthy eating behaviour and weight gain trajectories, and evidence is starting to build surrounding the method. This review brings together all empirical evidence to date examining behaviours associated with the approach, its outcomes and confounding factors.SummaryOverall, although there is limited evidence suggesting that a baby-led approach may encourage positive outcomes, limitations of the data leave these conclusions weak. Further research is needed, particularly to explore pathways to impact and understand the approach in different contexts and populations

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure

A controlled trial of the effectiveness of a diabetes education programme in a multi-ethnic community in Glasgow [ISRCT28317455]

BACKGROUND: Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin. Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population. The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes. We then investigated whether this intervention could produce an improvement, and finally whether any improvement was greater than background changes in knowledge in comparison groups. METHODS: A multi-site prospective, randomised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow, Scotland. The intervention consisted of 18 educational sessions in 6 separate programmes. A modified questionnaire was used to measure the knowledge, attitudes, and practice of diabetes before and after intervention. RESULTS: Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes, regarded the disease less seriously, and had a lesser understanding of the relationship between control and complications than the white population. No differences in initial responses were found between those who completed the second assessment and those who did not. The intervention group showed significant improvements in scores for Knowledge (+12.5%); Attitudes toward seriousness (+13.5%), complications (+8.1%), Practice (+20.0%). However there were also changes in the ethnic control group scores; respectively +5.0%, +16.3% (significant P < 0.001), +1.5%, +1.7%. The single white control group also showed some improvements; respectively +12.2%, +12.4% (P = 0.04), +6.0%, +25.0% (P = 0.007), but the differences in improvement between these two control groups were not significant. Overall, the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change (P = 0.36 CI -0.9 to +2.6). CONCLUSION: This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice. However there was no net benefit compared with the control group

The MACHO Project Large Magellanic Cloud Variable Star Inventory. VIII. The Recent Star Formation History of the LMC from the Cepheid Period Distribution

We present an analysis of the period distribution of $\sim 1800$ Cepheids in the Large Magellanic Cloud, based on data obtained by the MACHO microlensing experiment and on a previous catalogue by Payne-Gaposchkin. Using stellar evolution and pulsation models, we construct theoretical period-frequency distributions that are compared to the observations. These models reveal that a significant burst of star formation has occurred recently in the LMC ($\sim 1.15\times 10^8$ years). We also show that during the last $\sim 10^8$ years, the main center of star formation has been propagating from SE to NW along the bar. We find that the evolutionary masses of Cepheids are still smaller than pulsation masses by $\sim 7$ % and that the red edge of the Cepheid instability strip could be slightly bluer than indicated by theory. There are $\sim 600$ Cepheids with periods below $\sim 2.5$ days cannot be explained by evolution theory. We suggest that they are anomalous Cepheids; a number of these stars are double-mode Cepheids

Stroke in Older Adults Living in Care Homes: Results From a National Data Linkage Study in Wales

Objectives: To determine the proportion of older people moving to care homes with a recent stroke, incidence of stroke after moving to a care home, mortality following stroke, and secondary stroke prevention management in older care home residents. Design: Retrospective cohort study using population-scale individual-level linked data sources between 2003 and 2018 in the Secure Anonymized Information Linkage (SAIL) Databank. Setting and Participants People aged ≥65 years residing in long-term care homes in Wales. Methods: Competing risk models and logistic regression models were used to examine the association between prior stroke, incident stroke, and mortality following stroke. Results: Of 86,602 individuals, 7.0% (n = 6055) experienced a stroke in the 12 months prior to care home entry. The incidence of stroke within 12 months after entry to a care home was 26.2 per 1000 person-years [95% confidence interval (CI) 25.0, 27.5]. Previous stroke was associated with higher risk of incident stroke after moving to a care home (subdistribution hazard ratio 1.83, 95% CI 1.57, 2.13) and 30-day mortality following stroke (odds ratio 2.18, 95% CI 1.59, 2.98). Severe frailty was not significantly associated with risk of stroke or 30-day mortality following stroke. Secondary stroke prevention included statins (51.0%), antiplatelets (61.2%), anticoagulants (52.4% of those with atrial fibrillation), and antihypertensives (92.1% of those with hypertension). Conclusions and Implications: At the time of care home entry, individuals with history of stroke in the previous 12 months are at a higher risk of incident stroke and mortality following an incident stroke. These individuals are frequently not prescribed medications for secondary stroke prevention. Further evidence is needed to determine the optimal care pathways for older people living in long-term care homes with history of stroke

Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.

Objective: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. Methods: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. Results: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001). Conclusions: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy

Comparisons of the factor structure and measurement invariance of the Spence children’s anxiety scale - parent version in children with autism spectrum disorder and typically developing anxious children

The Spence Children’s Anxiety Scale - Parent version (SCAS-P) is often used to assess anxiety in children with autism spectrum disorder (ASD), however, little is known about the validity of the tool in this population. The aim of this study was to determine whether the SCAS-P has the same factorial validity in a sample of young people with ASD (n=285), compared to a sample of typically developing young people with anxiety disorders (n=224). Poor model fit with all of the six hypothesised models precluded invariance testing. Exploratory factor analysis indicated that different anxiety phenomenology characterises the two samples. The findings suggest that cross-group comparisons between ASD and anxious samples based on the SCAS-P scores may not always be appropriat

A structured review of reasons for ecstasy use and related behaviours: pointers for future research

Abstract Background While the health risks of using ecstasy warrant intervention development, a recent meta-analysis of determinants of ecstasy use identified a number of lacunae in the literature. Specifically, no studies were included that address behaviours other than 'using ecstasy' (e.g. 'trying out ecstasy' or 'ceasing ecstasy use'). However, because meta-analyses aim to integrate study results quantitatively, the resulting rigid exclusion criteria cause many studies to be discarded on the basis of their qualitative methodology. Such qualitative studies may nonetheless provide valuable insights to guide future research. To provide an overview of these insights regarding ecstasy use, the current study summarizes and combines what is known from qualitative and exploratory quantitative literature on ecstasy use. Methods The databases PsycINFO and MedLine were searched for publications reporting reasons for ecstasy use and related behaviour, and the results were structured and discussed per behaviour and compared over behaviours. Results Two main categories of reasons were found. The first category comprised reasons to start using ecstasy, use ecstasy, use ecstasy more often, and refrain from ceasing ecstasy use. The second category comprised reasons to refrain from starting to use ecstasy, use less ecstasy, and cease using ecstasy. Reasons for related behaviours within each of these two categories appear to differ, but not as substantially as between the two categories. A large number of reasons that were not yet explored in quantitative research emerged. Conclusion The current summary and combination of exploratory studies yields useful lists of reasons for each behaviour. Before these lists can inform interventions, however, they beg quantitative verification. Also, similarity of determinant configurations of different behaviours can be assessed by addressing determinants of several behaviours in one study. Another important finding is that meta-analytical integration of the literature may overlook important findings and implications. Thus, qualitative reviews remain useful instruments in setting the research agenda.</p