Virgin Care

We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.

BACKGROUND: Despite being a core business of medicine, end of life care (EoLC) is neglected. It is hampered by research that is difficult to conduct with no common standards. We aimed to develop evidence-based guidance on the best methods for the design and conduct of research on EoLC to further knowledge in the field. METHODS: The Methods Of Researching End of life Care (MORECare) project built on the Medical Research Council guidance on the development and evaluation of complex circumstances. We conducted systematic literature reviews, transparent expert consultations (TEC) involving consensus methods of nominal group and online voting, and stakeholder workshops to identify challenges and best practice in EoLC research, including: participation recruitment, ethics, attrition, integration of mixed methods, complex outcomes and economic evaluation. We synthesised all findings to develop a guidance statement on the best methods to research EoLC. RESULTS: We integrated data from three systematic reviews and five TECs with 133 online responses. We recommend research designs extending beyond randomised trials and encompassing mixed methods. Patients and families value participation in research, and consumer or patient collaboration in developing studies can resolve some ethical concerns. It is ethically desirable to offer patients and families the opportunity to participate in research. Outcome measures should be short, responsive to change and ideally used for both clinical practice and research. Attrition should be anticipated in studies and may affirm inclusion of the relevant population, but careful reporting is necessitated using a new classification. Eventual implementation requires consideration at all stages of the project. CONCLUSIONS: The MORECare statement provides 36 best practice solutions for research evaluating services and treatments in EoLC to improve study quality and set the standard for future research. The statement may be used alongside existing statements and provides a first step in setting common, much needed standards for evaluative research in EoLC. These are relevant to those undertaking research, trainee researchers, research funders, ethical committees and editors.

Increasing antibacterial resistance in Neisseria gonorrhoeae is threatening the success of routine treatment. This letter describes the clinical failure of ceftriaxone and azithromycin in a patient with gonorrhea.

The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed evidence-based guidance for the use of home oxygen for patients out of hospital. Although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease, the scope of the guidance includes patients with a variety of long-term respiratory illnesses and other groups in whom oxygen is currently ordered, such as those with cardiac failure, cancer and end-stage cardiorespiratory disease, terminal illness or cluster headache. It explores the evidence base for the use of different modalities of oxygen therapy and patient-related outcomes such as mortality, symptoms and quality of life. The guideline also makes recommendations for assessment and follow-up protocols, and risk assessments, particularly in the clinically challenging area of home oxygen users who smoke. The guideline development group is aware of the potential for confusion sometimes caused by the current nomenclature for different types of home oxygen, and rather than renaming them, has adopted the approach of clarifying those definitions, and in particular emphasising what is meant by long-term oxygen therapy and palliative oxygen therapy. The home oxygen guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.

BACKGROUND: Cognitive-behavioral therapy (CBT) is first choice of treatment for depressive symptoms and disorders in adolescents, however improvements are necessary because overall efficacy is low. Insights on CBT components and contextual and structural characteristics might increase the efficacy. The aim of our approach is to evaluate the efficacy of CBT for youth with depression and investigate the influence of specific components, contextual and structural factors that could improve effects. METHODS: A systematic review of randomized controlled trials was conducted, searches were undertaken in CINAHL, CENTRAL, EMBASE, MEDLINE/PubMed and PsycINFO. Outcomes were meta-analyzed and confidence in results was assessed using the GRADE-method. Meta-regression was used to pinpoint components or other factors that were associated with an in- or decrease of effects of CBT. RESULTS: We included 31 trials with 4335 participants. Moderate-quality evidence was found for CBT reducing depressive symptoms at the end of treatment and at follow-up, and CBT as indicated prevention resulted in 63% less risk of being depressed at follow-up. CBT containing a combination of behavioral activation and challenging thoughts component (as part of cognitive restructuring) or the involvement of caregiver(s) in intervention were associated with better outcomes for youth on the long term. CONCLUSIONS: There is evidence that CBT is effective for youth with a (subclinical) depression. Our analyses show that effects might improve when CBT contains the components behavioral activation and challenging thoughts and also when the caregiver(s) are involved. However, the influential effects of these three moderators should be further tested in RCTs.

is possible because of proximity to others with contagious diseases (ie, resulting from direct person-to-person transmission).

Leadership is one of the most complex and multidimensional phenomena. It has been studied extensively over the years and has taken on greater importance than ever before in today’s fast-paced and increasingly globalised world. Nonetheless, leadership continues to generate captivating and confusing debate due to the complexity of the subject. Bennis notes that ‘leadership is the most studied and least understood topic of any in the social sciences’ and ‘never have so many laboured so long to say so little’.1 Researchers have proposed many different definitions and theories of leadership. Stogdill defines it as ‘an influencing process aimed at goal achievement’, focusing on leadership as a process directed at influencing a specific group of people to meet a stated objective.2 Kouzes and Posner similarly believe that ‘leadership is the art of mobilising others to want to struggle for the shared aspirations’3 and Maxwell states that leadership is simply influence.4 Yet there is no one definition or particular leadership approach that is considered universal and efforts continue in trying to identify what makes an effective leader. Effective leadership is recognised as key to the success of any organisation. In fact, there has been a shift towards acknowledging the importance of human capital and organisational management.5 6 But what is the difference between leadership and management? Leaders are generally viewed as visionaries and strategist whereas managers monitor and control performance, maintaining order and stability in an organisation.7 8 Some researchers argue that leaders and managers have distinct roles and responsibilities while others assert that leadership and management are complementary and it would be difficult to separate them in practice.7 The present paper traces the historical evolution of the main leadership theories and reviews the progress that has been made over the years. It explores four …

This report is the third and final one of the series on water-loss investigations conducted jointly by several Federal agencies during the years 1950-53. Previous reports are water-loss investigations: Lake

Frailty is associated with increased mortality both before and after liver transplantation (LT). There are no standardized exercise programs, in particular home-based exercise programs (HBEPs), for patients awaiting LT. The aim was to investigate the feasibility of such a program in patients awaiting LT. Patients were randomly selected from the Birmingham LT waiting list and provided with a 12-week HBEP, including average daily step (ADS) targets and twice-weekly resistance exercises. Feasibility was based on patient eligibility (≥66% of waiting list), target recruitment (≥90% of n = 20), safety (no related serious adverse events), and adherence (≥66% adherence to 6-week HBEP). Measures of aerobic (incremental shuttle walk test [ISWT], ADS), functional capacity (short physical performance battery test [SPPBT]), and health-related quality of life (EuroQol 5-Dimension 5-Level (EQ-5D-5L) and hospital anxiety and depression score [HADS]) were taken at baseline and at 6 and 12 weeks. 18 patients (50% male; median age, 55 years) were recruited. All domains of the study feasibility criteria were met. ISWT improved after 6 weeks (50 m; P ≤ 0.01) and 12 weeks (210 m; P ≤ 0.01), despite withdrawal of the telephone health calls. Similarly, improvements were seen in ADS (2700/day; P ≤ 0.01) and the SPPBT (2.5; P = 0.02) after 12 weeks. There was no difference in HADS (median difference [MD] -3; P = 0.69), but EQ-5D-5L after 12 weeks (17.5%; P = 0.04). In conclusion, a 12-week HBEP, incorporating both easy-to-apply resistance and aerobic exercises, is safe and feasible in patients awaiting LT. Measures of aerobic and functional capacity demonstrate trends toward improvement that warrant further investigation in a randomized controlled trial.

whiK was one of five new whi loci identified in a recent screen of NTG-induced whi mutants and was defined by three mutants, R273, R318 and R655. R273 and R318 produce long, tightly coiled aerial hyphae with frequent septation. In contrast, R655 shows a more severe phenotype; it produces straight, undifferentiated aerial hyphae with very rare short chains of spores. Subcloning and sequencing showed that whiK encodes a member of the FixJ subfamily of response regulators, with a C-terminal helix-turn-helix DNA-binding domain and an apparently typical N-terminal phosphorylation pocket. Unexpectedly, a constructed whiK null mutant failed to form aerial mycelium, showing that different alleles of this locus can arrest Streptomyces coelicolor development at very distinct stages. As a consequence of the null mutant phenotype, whiK was renamed bldM. The bldM null mutant fits into the extracellular signalling cascade proposed for S. coelicolor and is a member of the bldD extracellular complementation group. The three original NTG-induced mutations that defined the whiK/bldM locus each affected the putative phosphorylation pocket. The mutations in R273 and in R318 were the same, replacing a highly conserved glycine (G-62) with aspartate. The more severe mutant, R655, carried a C-7Y substitution adjacent to the highly conserved DD motif at positions 8-9. However, although bldM has all the highly conserved residues associated with the phosphorylation pocket of conventional response regulators, aspartate-54, the putative site of phosphorylation, is not required for bldM function. Constructed mutant alleles carrying either D-54N or D-54A substitutions complemented the bldM null mutant in single copy in trans, and strains carrying the D-54N or the D-54A substitution at the native chromosomal bldM locus sporulated normally. bldM was not phosphorylated in vitro with either of the small-molecule phosphodonors acetyl phosphate or carbamoyl phosphate under conditions in which a control response regulator protein, NtrC, was labelled efficiently.

BACKGROUND: Croup (laryngotracheobronchitis) is a common cause of upper airway obstruction in children with a peak incidence of 60 per 1000 child years in those aged between one and two years. It is characterised by hoarseness, a barking cough, and inspiratory stridor. These symptoms are thought to occur as a result of oedema of the larynx and trachea, which have been triggered by a recent viral infection. Para influenza virus type 1 is the agent most commonly identified in cases of croup. Severe cases are admitted to hospital and steroid treatment is established to reduce disease severity. Treatment with humidified air was previously widely used and is still commonly recommended as home treatment. OBJECTIVES: To assess the efficacy of humidified air in the treatment of croup. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to January 2006) and EMBASE (1990 to January 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving children suffering from croup treated with humidified air. DATA COLLECTION AND ANALYSIS: Two authors independently identified potentially relevant abstracts identified from the search and then assessed the full papers for inclusion and methodological quality. Outcome measures included mortality, ventilation, admission to hospital, re-contact with medical services, number of days off school and relief of symptoms; these were separately analysed for the week following treatment. Data extraction was performed by the two authors then entered by one and checked by the second author. Missing data were obtained from trails authors where possible. Data were analysed using Review Manager version 4.2. Sensitivity and sub-group analysis were not possible due to the paucity of trials. MAIN RESULTS: Three studies in emergency settings provided data on 135 patients with moderate croup for the main outcome (croup score). The combined results from 20 to 60 minutes in the three studies marginally favoured the treatment group with a weighted standardised mean difference of -0.14 (95% confidence interval (CI) -0.75 to 0.47). No other outcomes were significantly different between the groups. AUTHORS' CONCLUSIONS: The croup score of children managed in an emergency setting with mild to moderate croup probably does not improve greatly with inhalation of humidified air. Further research is needed in primary care settings, using a wider range of more sensitive outcome measures.

the long-running, deeply tragic and emotionally fraught case of Charlie Gard reached its sad conclusion (box 1). Following further medical assessment of the infant, Charlie's parents and doctors finally reached agreement that continuing medical treatment was not in Charlie's best interests. Life support was subsequently withdrawn and Charlie died on 28 July 2017.

There has been a dramatic increase in the number of sufferers of chronic childhood diseases surviving into adulthood. Effective transition of these children from paediatric to adult medical services is a considerable challenge. A lack of integrated planning for this event can present barriers to successful transition. These barriers may be generated by the patient, his family or by political or logistical factors. However, physicians themselves can also become barriers in this process. Paediatricians may resist the transition process as they lack confidence in their adult colleagues. Emotional, academic, financial and cultural issues will also influence both child and adult physician's attitude to the hand-over of care. Increasingly poor understanding of their disease process by Paediatric trained doctors, makes transfer of care essential for adolescents. The move towards a culture of personal responsibility for health care is also crucial for the promotion of the maturing patient's independence. Development of adolescent services and closer links between the services could do much to enhance the transition experience of emerging adults.

Abstract The lockdown measures put in place in March 2020 in England to counter the spread of the coronavirus have had significant implications for the lives and well‐being of young carers and young adult carers. In such unprecedented times, little was known about the potential impact on this group and their specific experience of the Covid‐19 lockdown restrictions. A rapid review was conducted, 28 young carers responded to a survey and an additional 20 participants were interviewed in January 2021; the survey was repeated with a further 149 responses. Findings show that the level of care that young carers are required to provide had increased as external agency support for their families had been withdrawn while their own coping strategies had been challenged, in particular through school closures. These restrictions had a significant impact on every aspect of their lives, from their ability to meet their own mental health needs to managing the requirements of home schooling. The needs of young carers should be acknowledged within the political agenda, especially at times of crisis. It is crucial that health and social care services increase their capacity to identify and support young carers and that work is done within educational settings to provide a flexible response to individual needs.

This document summarizes the current consensus opinion of the Exaggerated Pharmacology (EP) Subcommittee of the Oligonucleotide Safety Working Group on the appropriate strategies to assess potential adverse effects caused by an "exaggerated" degree of the intended pharmacologic activity of an oligonucleotide (ON). The Subcommittee focused its discussions primarily on the ON subclasses that impact expression of "host" (i.e., human gene products--antisense, small interfering RNAs, and related ONs that target messenger RNA), with later and more limited discussions on aptamer, immunostimulatory, and microRNA subclasses. It is expected that many of these principles will be relevant to other subclasses but will need to be carefully considered as those development programs advance towards clinical trials. The recommendations may also serve as a frame of reference when designing Good Laboratory Practice safety studies with ONs, with regard to the study design elements that address assessment of EP. It is also hoped that these recommendations will establish a foundation for discussion with regulatory agencies on this subject.

There exists wide variation in practice regarding the use of chaperones for physical examination of the patient in primary care. Guidelines agree that a chaperone should be offered or used whenever a patient is undergoing an intimate examination. This paper aims to gauge patient views on the use of chaperones in primary care. Focus groups were used to identify themes surrounding the use of chaperones in primary care. Questionnaires were then mailed to 404 women and 400 men aged 16 years to 65 years identified from the lists of three research practices in the Northern and Yorkshire Region. The most important factor for the patient in an intimate examination is the attitude of the doctor; the patient views the offer of a chaperone as a sign of respect by the doctor. The development of shared decision-making within a consultation involving an intimate examination should be seen as more important than a rigid approach towards using a chaperone.

The first 8 weeks of pregnancy is a critical time, with the majority of pregnancy losses occurring during this period. Abnormal chromosome number (aneuploidy) is a common finding in human miscarriage, yet is rarely reported in domestic animals. Equine early pregnancy loss (EPL) has no diagnosis in over 80% of cases. The aim of this study was to characterise aneuploidies associated with equine EPL. Genomic DNA from clinical cases of spontaneous miscarriage (EPLs; 14-65 days of gestation) and healthy control placentae (various gestational ages) were assessed using a high density genotyping array. Aneuploidy was detected in 12/55 EPLs (21.8%), and 0/15 healthy control placentae. Whole genome sequencing (30X) and digital droplet PCR (ddPCR) validated results. The majority of these aneuploidies have never been reported in live born equines, supporting their embryonic/fetal lethality. Aneuploidies were detected in both placental and fetal compartments. Rodents are currently used to study how maternal ageing impacts aneuploidy risk, however the differences in reproductive biology is a limitation of this model. We present the first evidence of aneuploidy in naturally occurring equine EPLs at a similar rate to human miscarriage. We therefore suggest the horse as an alternative to rodent models to study mechanisms resulting in aneuploid pregnancies.

OBJECTIVE: To consider the feasibility of setting up a relaxation group to treat symptoms of post stroke anxiety in an in-patient post-acute setting; and to explore the effectiveness of relaxation training in reducing self-reported tension. METHOD: A relaxation group protocol was developed in consultation with a multidisciplinary team and a user group. Over a period of 24 months, 55 stroke patients attended group autogenic relaxation training on a rehabilitation ward. Attendance ranged between one and eleven sessions. Self-reported tension was assessed pre and post relaxation training using the Tension Rating Circles (TRCs). RESULTS: The TRCs identified a significant reduction in self-reported tension from pre to post training, irrespective of the number of sessions attended; z = -3.656, p < 0.001, r = -0.67, for those who attended multiple sessions, z = -2.758, p < 0.01, r = -0.6 for those who attended a single session. DISCUSSION: The routine use of relaxation techniques in treating anxiety in patients undergoing post-stroke rehabilitation shows potential. Self-reported tension decreased after attendance at relaxation training. The TRCs proved acceptable to group members, but should be validated against standard anxiety measures. Further exploration of the application of relaxation techniques in clinical practice is desirable. Implications for Rehabilitation Anxiety is prevalent after stroke and likely affects rehabilitation outcomes. Relaxation training is a well proven treatment for anxiety in the non-stroke population. A significant within session reduction in tension, a hallmark symptom of anxiety, was evidenced via group relaxation training delivered in a post-acute, in-patient stroke unit setting. Relaxation training a shows promise as a treatment for anxiety after stroke.

Cardiac output is considered an important parameter when assessing the cardiovascular status of a critically ill patient. Both non-invasive (e.g. bioimpedance, echocardiography) and invasive methods (Swan Ganz catheter) have been used to measure cardiac output. The ultrasonic cardiac output monitoring device provides a new method of non-invasively assessing cardiac output in various clinical settings. The ultrasonic cardiac output monitoring device was introduced clinically in 2001, and appears to be a promising adjunct in the assessment of the cardiovascular state in a variety of patient cohorts. In this short review article, we will introduce this new technique, discuss the required skills and compare it with methods already in use. In particular, a critical comparison with the 'gold standard', the invasive measurement of cardiac output with the pulmonary artery catheter, will be given.

Purpose of review Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) with the focus of promoting physical activity and prescribing exercise within four domains, outlined recently by the European League against Rheumatism (EULAR): aerobic, resistance, flexibility and neuro-motor exercise. There is an increasing evidence base to support physical therapy interventions in axSpA. Recent findings We present evidence supporting the use of exercise as treatment for patients with axSpA, recent updates among different exercise modalities, and make clear its critical place in the management of this condition. Recent large, multicentre data have shown that high-intensity exercise can improve disease activity and also positively impact cardiovascular risk factors in these patients. Although international treatment guidelines advocate the inclusion of physical activity and exercise for the optimal management of axSpA, specific guidance about the amount of exercise required to produce a beneficial effect is lacking. Summary Exercise must be used in the management of axSpA, and whilst hydrotherapy and flexibility exercises are traditionally the main focus, other applications, such as strength training, may be underutilized domains. Further studies are needed to determine the dose–response relationship between exercise and axSpA patient subsets.