Managing loneliness: a qualitative study of older people's views.

Engaging with older people who self-identify as lonely may help professionals in mental health and other services understand how they deal with loneliness. The evidence-base for effective interventions to address loneliness is inconclusive. This study aimed to explore how community-dwelling lonely older people in England manage their experiences of loneliness. Twenty eight community-dwelling older people identifying as lonely, based on responses to two loneliness measures (self-report and a standardised instrument), participated in in-depth interviews between 2013 and 2014. Fifteen lived alone. Thematic analysis of transcribed interviews was conducted by a multidisciplinary team including older people.Participants drew on a range of strategies to ameliorate their distress which had been developed over their lives and shaped according to individual coping styles and contexts. Strategies included physical engagement with the world beyond their home, using technologies, planning, and engagement with purpose in an 'outside world', and acceptance, endurance, revealing and hiding, positive attitude and motivation, and distraction within an 'inside world'. Strategies of interests and hobbies, comparative thinking, religion and spirituality and use of alcohol straddled both the inside and outside worlds. Participants conveyed a personal responsibility for managing feelings of loneliness rather than relying on others. This study includes the experiences of those living with loneliness whilst also living with other people. When developing policy and practice responses to loneliness it is important to listen attentively to the views of those who may not be engaging with services designed for 'the lonely' and to consider their own strategies for managing it.

Patient-centred value framework for haemophilia.

INTRODUCTION: Growing budgetary demands have led to increased scrutiny of healthcare spending for rare diseases, leading to a unified goal within the haemophilia community to define objectively patient-centred value in haemophilia care. AIM: To develop a patient-centred outcomes framework with global applicability for assessing value in haemophilia healthcare. METHODS: An international, multidisciplinary panel of experts convened to identify the range of patient impacts of haemophilia health care and organize these into a three-tiered, patient-centred outcomes framework based on Porter's model for assessing value. RESULTS: In addition to measures common to other chronic diseases (eg survival and quality of life), Tier 1, health status achieved or retained, includes haemophilia-specific outcomes of bleeding frequency, musculoskeletal complications and life-threatening bleeds, as well as measures of function or activity. Tier 2, process of recovery, includes such outcomes as time to initial treatment, time to recovery and time missed at education/work; also included are disutility of care, measured by inhibitor development, pathogen transmission/infections, orthopaedic intervention and difficult venous access. Tier 3, sustainability of health, is measured by bleed avoidance, maintenance of productive lives and good health over time; potential long-term negative consequences include insufficient or inappropriate therapy and age-related complications. The applicability of the outcomes framework for different types of haemophilia healthcare interventions is described. CONCLUSION: Haemophilia health care can affect multiple patient-centred outcomes across diverse patient types and healthcare systems. This framework organizes those outcomes for informing value-based decision making by multiple stakeholders and provides the basis for further refinement and development of a standardized outcomes set.

Asymmetric Synthesis of ß-Amino Amides by Catalytic Enantioconvergent 2-Aza-Cope Rearrangement.

Dynamic kinetic resolutions of α-stereogenic-ß-formyl amides in asymmetric 2-aza-Cope rearrangements are described. Chiral phosphoric acids catalyze this rare example of a non-hydrogenative DKR of a ß-oxo acid derivative. The [3,3]-rearrangement occurs with high diastereo- and enantiocontrol, forming ß-imino amides that can be deprotected to the primary ß-amino amide or reduced to the corresponding diamine.

Enantioconvergent synthesis of functionalized γ-butyrolactones via (3 + 2)-annulation.

A dynamic kinetic resolution of ß-halo α-keto esters in an asymmetric homoenolate reaction is described. A chiral N-hetereocyclic carbene catalyzes the a(3) → d(3)-umpolung addition of α,ß-enals to racemic α-keto esters, forming γ-butyrolactones with three contiguous stereocenters. The addition occurs with high regio-, diastereo-, and enantiocontrol. This methodology constitutes an intermolecular DKR process to set three stereocenters during the key bond forming event.

Using multi-country household surveys to understand who provides reproductive and maternal health services in low- and middle-income countries: a critical appraisal of the Demographic and Health Surveys.

OBJECTIVE: The Demographic and Health Surveys (DHS) are a vital data resource for cross-country comparative analyses. This study is part of a set of analyses assessing the types of providers being used for reproductive and maternal health care across 57 countries. Here, we examine some of the challenges encountered using DHS data for this purpose, present the provider classification we used, and provide recommendations to enable more detailed and accurate cross-country comparisons of healthcare provision. METHODS: We used the most recent DHS surveys between 2000 and 2012; 57 countries had data on family planning and delivery care providers and 47 countries had data on antenatal care. Every possible response option across the 57 countries was listed and categorised. We then developed a classification to group provider response options according to two key dimensions: clinical nature and profit motive. RESULTS: We classified the different types of maternal and reproductive healthcare providers, and the individuals providing care. Documented challenges encountered during this process were limitations inherent in household survey data based on respondents' self-report; conflation of response options in the questionnaire or at the data processing stage; category errors of the place vs. professional for delivery; inability to determine whether care received at home is from the public or private sector; a large number of negligible response options; inconsistencies in coding and analysis of data sets; and the use of inconsistent headings. CONCLUSIONS: To improve clarity, we recommend addressing issues such as conflation of response options, data on public vs. private provider, inconsistent coding and obtaining metadata. More systematic and standardised collection of data would aid international comparisons of progress towards improved financial protection, and allow us to better characterise the incentives and commercial nature of different providers.

Dynamic kinetic asymmetric cross-benzoin additions of ß-stereogenic α-keto esters.

The dynamic kinetic resolution of ß-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted ß-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads.

Population-based linkage of health records to detect urological complications and hospitalisation following transrectal ultrasound-guided biopsies in men suspected of prostate cancer.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy is a common urological procedure with known complications. We determined the urological complication and 30-day hospital admission rate in a population-based cohort using unique identifier and deterministic methodology of record linkage. METHODS: 715 men who underwent a transrectal ultrasound-guided biopsy in Tayside region of Scotland between April 2007 and September 2011 were identified from hospital records using their unique Community Health Index Number. Multiple hospital electronic databases (Central Vision, Insite, Wisdom, and TOPAS) and departmental-based resources (morbidity and mortality records, daily ward electronic records) were linked to estimate urological complications (urinary tract infection, urinary retention, haematuria) and rates of hospital admission. Cross-validation of information was obtained by searching a drug dispensing information network and microbiology database for infective complications. The hospital admission rate was compared for two different prophylactic antibiotic regimens used during the study period. RESULTS: Of the 715 men who underwent transrectal ultrasound biopsy, 386 (53.9 %) were diagnosed with prostate cancer and 329 (46.1 %) were found to have benign histology. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.95 % (14/715). The 30-day hospital admission rate was not different for different regimens of prophylactic antibiotics. There were 50 (6.99 %; 50/715) urine cultures requested to the microbiology department within 30 days of procedures; out of which 20 (2.79 %; 20/715) were positive. Most of these were generated from general practice requests. Eight blood cultures obtained within the same period were all negative. Eleven patients (1.7 %) presented with urinary retention during the same period and required indwelling catheterisation. None of them had any surgical procedure. Validation of electronic record linkage against telephonic questionnaires by specialist nurse showed a high reliability of the methodology (κ = 0.91). CONCLUSION: High quality validated record linkage of cohort data in the present study using a unique identifier, protocol-based procedure and antibiotic prophylaxis showed that hospitalisation following TRUS biopsies occurs in less than 2 % of patients. However, a significant number of patients report to primary care, and centrally held records based on coding alone could underestimate the true incidence of complications.

Experiments probing the viability of donor-acceptor norbornenes for (5 + 2)-annulation.

This Note details experiments that probe the mechanism by which donor-acceptor norbornene systems epimerize. A number of mechanistic studies indicate that epimerization in these systems occurs via a Lewis acid catalyzed retro-Diels-Alder/Diels-Alder sequence, rather than bond rotation in an intimate ion pair. These results suggest that, under the reaction conditions examined, the ring strain present in norbornene is inadequate to induce zwitterion formation analogous to that observed with donor-acceptor cyclopropanes.

Training environment and Vitamin D status in athletes.

This study assessed the associations between gender, anthropometry, predominant training environment and Vitamin D status in 72 elite athletes. Additionally, any links between Vitamin D status and recent injury/health status, or sun protection practices were investigated. Athletes underwent an anthropometric assessment and provided venous blood samples for the determination of 25-hydroxyvitamin D (25(OH)D), the accepted biological marker of Vitamin D status. Finally, athletes completed a questionnaire relating to their recent training and injury history, and their sun protection practices. The athlete cohort were divided by predominant training environment as either indoor, outdoor, or mixed training environment athletes. The average ( ± SD) 25(OH)D levels of the group were 111 ± 37 nmol/L, with the indoor training group (90 ± 28 nmol/L) significantly lower than the outdoor (131 ± 35 nmol/L), and mixed (133 ± 29 nmol/L) training groups (p = 0.0001). Anthropometrical measures were positively associated with 25(OH)D levels; however, recent injury status or sun protection practice showed no association. Given the significant differences in 25(OH)D levels between the outdoor and indoor predominant training environments, coaches of indoor athletes may wish to monitor their athletes' Vitamin D levels throughout the year, in order to avoid any possibilities of a deficiency occurring.

Asymmetric synthesis of diverse glycolic acid scaffolds via dynamic kinetic resolution of α-keto esters.

The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse ß-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of ß-aryl- and ß-chloro-α-keto esters.

Drug dispensing practices during implementation of artemisinin-based combination therapy at health facilities in rural Tanzania, 2002-2005.

OBJECTIVE: To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. METHODS: Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271, 953 patient encounters in the three districts. RESULTS: In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. CONCLUSIONS: The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.

Closing the UK care home data gap - methodological challenges and solutions.

UK care home residents are invisible in national datasets. The COVID-19 pandemic has exposed data failings that have hindered service development and research for years. Fundamental gaps, in terms of population and service demographics coupled with difficulties identifying the population in routine data are a significant limitation. These challenges are a key factor underpinning the failure to provide timely and responsive policy decisions to support care homes. In this commentary we propose changes that could address this data gap, priorities include: (1) Reliable identification of care home residents and their tenure; (2) Common identifiers to facilitate linkage between data sources from different sectors; (3) Individual-level, anonymised data inclusive of mortality irrespective of where death occurs; (4) Investment in capacity for large-scale, anonymised linked data analysis within social care working in partnership with academics; (5) Recognition of the need for collaborative working to use novel data sources, working to understand their meaning and ensure correct interpretation; (6) Better integration of information governance, enabling safe access for legitimate analyses from all relevant sectors; (7) A core national dataset for care homes developed in collaboration with key stakeholders to support integrated care delivery, service planning, commissioning, policy and research. Our suggestions are immediately actionable with political will and investment. We should seize this opportunity to capitalise on the spotlight the pandemic has thrown on the vulnerable populations living in care homes to invest in data-informed approaches to support care, evidence-based policy making and research.

Development and characterization of promoterless helper RNAs for the production of alphavirus replicon particle.

Alphavirus-based replicon systems are frequently used as preclinical vectors and as antigen discovery tools, and they have recently been assessed in clinical vaccine trials. Typically, alphavirus replicon RNAs are delivered within virus-like replicon particles (VRP) that are produced following transfection of replicon RNA and two helper RNAs into permissive cells in vitro. The non-structural proteins expressed from the replicon RNA amplify the replicon RNA in cis and the helper RNAs in trans, the latter providing the viral structural proteins necessary to package the replicon RNA into VRP. Current helper RNA designs incorporate the alphavirus 26S promoter to direct the transcription of high levels of structural gene mRNAs. We demonstrate here that the 26S promoter is not required on helper RNAs to produce VRP and propose that such promoterless helper RNAs, by design, reduce the probability of generating replication-competent virus that may otherwise result from RNA recombination.

Policy interventions that attract nurses to rural areas: a multicountry discrete choice experiment.

OBJECTIVE: To evaluate the relative effectiveness of different policies in attracting nurses to rural areas in Kenya, South Africa and Thailand using data from a discrete choice experiment (DCE). METHODS: A labelled DCE was designed to model the relative effectiveness of both financial and non-financial strategies designed to attract nurses to rural areas. Data were collected from over 300 graduating nursing students in each country. Mixed logit models were used for analysis and to predict the uptake of rural posts under different incentive combinations. FINDINGS: Nurses' preferences for different human resource policy interventions varied significantly between the three countries. In Kenya and South Africa, better educational opportunities or rural allowances would be most effective in increasing the uptake of rural posts, while in Thailand better health insurance coverage would have the greatest impact. CONCLUSION: DCEs can be designed to help policy-makers choose more effective interventions to address staff shortages in rural areas. Intervention packages tailored to local conditions are more likely to be effective than standardized global approaches.

Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity.

A series of dimeric 1,3-cyclohexanedione oxime ethers were synthesized and found to have significant antiplasmodial activity with IC(50)'s in the range 3-12 microM. The most active dimer was tested in the Plasmodium berghei mouse model of malaria and at a dose of 48 mg/kg gave a 45% reduction in parasitaemia. Several commercial herbicides, all known to be inhibitors of maize acetyl-CoA carboxylase, were also tested for antimalarial activity, but were essentially inactive with the exception of butroxydim which gave an IC(50) of 10 microM.

Effects of caffeine on repeated sprint ability, reactive agility time, sleep and next day performance.

AIM: This study assessed the effects of caffeine on repeated sprint ability (RSA), reactive agility time (RAT), sleep and next day exercise performance. METHODS: Ten moderately trained male athletes (single-blind, randomized, crossover design) ingested either caffeine (6 mg.kg-1 bm) or placebo 1 h before exercise. Trials were performed on the same day one week apart. Performance measures included a RAT test (10 trials¥10.2 m, separated by 30 s), followed by 7 min of active recovery and then a RSA test (five sets of 6¥20 m sprints with 25 or 60 s of recovery). The RSA was then followed by 5 min of active recovery and another RAT. That night, participants wore a wrist sleep actigraph to bed. Next day, participants repeated the RAT and the first set of the RSA tests. RESULTS: Significant improvements were demonstrated after caffeine ingestion compared to placebo for the combined total time of each set (TT; combined sets 1, 3, 5; 58.947±1.88 vs. 59.683±2.54 s, respectively; P=0.05), best sprint time (BT; next day performance; 3.176±0.10 vs. 3.230±0.12 s, respectively, P=0.01), and % decrement (combined sets 2, 4; 2.866±1.24 vs. 3.801±1.69 s, respectively; P=0.02). Moderate to strong effect sizes were found for % decrement for set 2 (Cohen's d=-0.82; 1.312±0.65 vs. 2.110±1.20 s for caffeine and placebo conditions, respectively) and for sets 2 and 4 combined (Cohen's d=-0.63; 2.866±1.24 vs. 3.801±1.69 for caffeine and placebo conditions, respectively). No significant differences were found for RAT or for sleep measures (P>0.05). CONCLUSION: Caffeine improved RSA, including next day performance, but had little effect on RAT or sleep parameters.

Training patterns and negative health outcomes in triathlon: longitudinal observations across a full competitive season.

AIM: Despite heavy training requirements, triathlon is a sport that is rapidly increasing in popularity. Yet, there is limited research detailing the relationship between training, the incidence of injuries and illness, psychological stress, overtraining and athlete burnout amongst triathletes. Six hypotheses relating inter-individual differences to training factors were generated to evaluate change in self-reported measures of these negative health outcomes over a training year. METHODS: Thirty, well-trained, triathletes (males n=20: age=27.1±9.1 years and females n=10: age=27.4±6.6 years) from a local triathlon club participated in this study. The study commenced during pre-season training, and involved weekly monitoring of each athlete until the end of the competitive season 45 weeks later. Linear Mixed Modelling was used for the analysis. RESULTS: Signs and symptoms of injury and illness (SAS) were significantly associated with increases in training factors (P≤0.05); however, greatest impact on SAS was produced by psychological stressors (P≤0.001). Common symptoms of overtraining were significantly affected by increases in exposure to both training and psychological stressors (P≤0.05). Mood disturbance was not significantly affected by training factors (P>0.05) but rather increases in psychological stressors (P≤0.001). Finally, each of the three athlete burnout subscales were significantly affected by both psychological (P≤0.001) stressors as well as varying combinations of training factors (P≤0.05). CONCLUSIONS: Exposure to stressors (either training or psychological) had significant effects on all negative health outcomes assessed.