A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Using the Patient Concerns Inventory in the identification of fatigue following treatment for head and neck cancer.

Fatigue has a profound impact on health-related quality of life (HRQOL). The aim of this study was to describe the clinical characteristics and HRQOL of head and neck cancer patients who raised the issue of fatigue on the Patient Concerns Inventory (PCI) at their review consultation. Eight consultants were randomized to use the PCI as part of a cluster-controlled trial. Patients also completed the University of Washington Quality of Life version 4 (UWQOL), EQ-5D-5L (EuroQol Group), and Distress Thermometer questionnaires. The study included 140 patients who attended clinics at a median of 108 (interquartile range 70-165) days after the end of treatment. The PCI item 'fatigue' was the sixth most commonly selected, by 29% (n=40). Those with advanced tumours were more likely to have selected the item (30/84, 36% vs 10/56, 18%; P=0.02), as were those treated with radiotherapy±chemotherapy (34/87, 39% vs 6/53, 11%; P<0.001). The PCI fatigue group reported significantly worse overall quality of life, social-emotional and physical function composite scores (UWQOL), Distress Thermometer, and EQ-5D-5L. PCI fatigue was common in those with sleeping, nausea, mood, depression, mobility, breathing, and energy level concerns. In conclusion, given the problems associated with fatigue, it is appropriate to screen and seek interventions that might help patients address this.

Using a patient prompt list to raise concerns in oncology clinics does not necessarily lead to longer consultations.

Head and neck oncology post-treatment consultations form a critical component of care in terms of support and surveillance. They occur frequently in the first few years and can place substantial demands on healthcare resources. However, they provide useful opportunities for patients to raise issues and receive tailored information and support. The aim of this paper was to assess whether completion of a 56-item patient prompt list (PCI - the Patient Concerns Inventory) immediately prior to the consultation significantly increased its duration. This was a pragmatic cluster preference randomised controlled trial of 288 patients with 15 consultant clusters from two sites "using" (n=8) or "not using" (n=7) the PCI. Consultation times were known for 283 patients (136 PCI, 147 non-PCI) who attended their first post-treatment trial consultation a median (IQR) of 103 (70-160) days after the end of treatment. Consultations lasted a median (IQR) of 10 (7-13) minutes (mean 11) in non-PCI patients and a median (IQR) of 11 (8-15) minutes (mean 12) in PCI patients (p=0.07). After adjustment for patient clustering and significant case mix, the 95% confidence interval for the mean difference was between 1.45minutes shorter with the PCI and 2.98minutes longer (p=0.50). There was significant variation in duration by consultant, tumour stage, treatment mode, overall quality of life (QoL), and distress (all p<0.001). In those who completed the PCI, duration increased with the total number of items selected (p<0.001). In conclusion, the inclusion of a prompt list to help facilitate conversation with patients did not make a substantial difference to consultation times.

Development and evaluation of a holistic surgical head and neck cancer post-treatment follow-up clinic using touchscreen technology-Feasibility study.

The efficacy of traditional follow-up care is being challenged, as cancer survivors' supportive and psychological needs are often neither identified, nor addressed. This study's aim was to develop a holistic surgical follow-up clinic for oral and oropharyngeal cancer patients were participants completed a disease-specific health-related quality of life tool (UWQOLv4) and item prompt list (Patient Concern Inventory) on a touchscreen computer. Information generated was used to focus the consultation on patient's identified needs and concerns. By means of a prospective non-randomised, pre-test post-test design, this follow-up clinic was evaluated using the patient enablement instrument (PEI) and patient content checklist (PCC). Feasibility was explored from the patient perspective (satisfaction survey) and clinician perspective (qualitative interview). Forty-four consecutive patients were recruited. Findings demonstrating five of the eight topics (overall QOL, emotions, head and neck symptoms, side-effects of treatment, chronic non-specific) on PCC were discussed more frequently, but changes were not statistically significant. The PEI highlighted a trend towards perceived improvement in four of the six items. Using touchscreen computers to aid communication during routine follow-up was reported as both feasible and beneficial by patients and clinicians. Providing a patient-focused follow-up consultation can facilitate the identification of unmet needs, permitting timely and appropriate intervention being initiated.

Fathers' experiences of living with cancer: a phenomenological study.

There is a paucity of knowledge about fathers' experiences of cancer. This study explored the experiences of fathers diagnosed and living with cancer while also having parental responsibility for children. A hermeneutic phenomenological approach guided the study. Data were generated through 22 in-depth interviews with 10 fathers throughout Northern Ireland. The findings evidenced that fathers' identities are challenged and frequently re-shaped by the cancer experience, in many cases leading to an improved lifestyle behaviour. Heightened engagement with their children can provide a protective effect from the illness. On the other hand a lack of involvement led to frustration and low mood. The findings also demonstrated that father/child relationships were adversely affected by the social complexities that exist in the variances and diversity of fathers parenting roles and status. This knowledge contributes to our understanding of the complex relationships of fathers in non-traditional roles. It extends our understanding of how, when stereotyped gendered roles are ascribed to fathers it can impact on a fathers' ability to fulfil the traditional breadwinner's role. This is knowledge that will inform health care professionals and enable them to provide gendered-sensitive care that takes account of the masculine psychological responses that can shape the cancer experience.

Quality of life considerations in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It identifies the current evidence base and role of health-related quality of life assessment for this group of patients. Recommendations • Health-related quality of life is integral to treatment planning, refining treatment protocols, and more personalised follow-up support. (G) • Health-related quality of life and patient concerns should be regularly assessed during patient care. (G) • Health-related quality of life assessment and patient concerns on an individual patient basis can be helpful to trigger multi-professional support and interventions. (G).

A national survey of healthcare professionals' views on models of follow-up, holistic needs assessment and survivorship care for patients with head and neck cancer.

Patterns of follow-up and survivorship care are changing in response to growing numbers of cancer survivors and an increasing recognition that traditional models are unsustainable and result in unmet needs. Clinicians have shown reluctance in changing conventional follow-up practices for patients with head and neck cancer. This study aimed to explore nurses' and allied health professionals' views and practices in relation to follow-up, holistic needs assessment and survivorship care in this patient group. An online survey of members of the British Association of Head and Neck Oncology Nurses was undertaken. The response rate was 43% (74 of 174). Findings revealed a range of existing models of follow-up, rehabilitation and support for people with head and neck cancer across the UK. Specialist staff were open to new models of care and to more responsibility, with adequate training and supervision. There were some gaps in the provision of comprehensive survivorship care and some specific areas of practice in which nurses lacked confidence, knowledge and skills, such as managing medications and complex symptoms. Further research is needed to develop and evaluate effective models of follow-up and support for a growing population of head and neck cancer survivors who have diverse and complex needs.

Fatherhood and cancer: a commentary on the literature.

When a parent is diagnosed with cancer it may create a multitude of concerns and worries, which can be enormously challenging. Despite the increase in research pertaining to parental cancer, there is a paucity of knowledge addressing the impact of cancer on fathers. Fathers' roles are evolving, becoming increasingly diverse and multidimensional. This paper aims to uncover some issues that may be relevant for fathers with cancer. A cancer diagnosis may not solely impact on a man's identity but also on the lives of his children given the contemporary shift from patriarch to more diverse roles. Men and women may share commonalities when diagnosed with cancer but they also experience differences emphasising the need for gender-sensitive care. This paper highlights the significant role and function that fathers have in their children's lives. It is important that healthcare professionals are aware and pay attention to how gendered responses shape fathers' masculinity and consequently the cancer experience and parenting role. Furthermore this paper highlights the need to gather additional evidence on fathers' experiences when diagnosed and living with cancer. This knowledge can then be used to inform healthcare policy to target fathers, which will benefit both fathers and their children.

Family life when a parent is diagnosed with cancer: impact of a psychosocial intervention for young children.

When a parent is diagnosed with cancer it can have a profound impact on the family, especially the children. This paper reports on the experience of parental cancer for parents' and their children and the impact of a psychosocial intervention for young children whose parent has cancer. Using a qualitative design, data were generated from separate focus groups with children (n = 7) and parents (n = 6). One-to-one interviews were conducted with professionals delivering the intervention (n = 2). Findings indicated that parents are often the gatekeeper to how, when and the context in which children learn about parental cancer. Many parents expressed a lack of confidence and skills as they considered communicating with their children about cancer. Parents stated the need for professional input mainly due to changes in their children's behaviour. Children had a number of fantasies and misconceptions surrounding cancer. This psychological intervention normalized their experience of parental cancer. It also improved children's understanding of cancer and equipped them with coping strategies. Professionals perceived the intervention led to improved family communication and promoted discussion of emotions. Open communication is pivotal for children whose parents have cancer but parents need supported and resourced to promote family coping when diagnosed with cancer.

European Board guidance for training centres in Internal Medicine.

The European Board of Internal Medicine is working towards enhancing the training in Internal Medicine in Europe. One of the most important tasks is to ensure that training programmes reach an acceptable level of quality. The Board does not accredit training centres as this is the responsibility of national authorities. The purpose of this paper is to provide guidance for the accreditation process. The content of the paper has been developed from a publication on medical education produced by the World Federation for Medical Education. Basic standards which should be met by all training centres are outlined. Quality development describes standards which centres should aim for although progress will to some extent be influenced by resources, stage of development and local circumstances.

Pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in healthy volunteers treated with trimethoprim-sulphamethoxazole.

OBJECTIVES: Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor under development for the treatment of human immunodeficiency virus-1 infection. This study was performed to investigate potential pharmacokinetic interactions between apricitabine and trimethoprim-sulphamethoxazole. METHODS: Pharmacokinetic parameters were calculated for single and multiple doses of apricitabine (and its metabolite BCH-335) in the presence and absence of steady-state concentrations of trimethoprim-sulphamethoxazole in healthy volunteers. RESULTS: Plasma concentrations and areas under the concentration-time curves of apricitabine and BCH-335 metabolite were higher when apricitabine was administered with trimethoprim-sulphamethoxazole than when apricitabine was given alone, both following single doses and during multipledosing. Apricitabine was well tolerated, both when given alone and with trimethoprim-sulphamethoxazole. CONCLUSIONS: These results suggest that exposure to apricitabine and its metabolite BCH-335 is moderately increased during co-administration with up to 960 mg q.d.s. trimethoprim-sulphamethoxazole. The size of this interaction does not appear to be influenced by the dose of trimethoprim-sulphamethoxazole and is consistent with that seen with other cytidine analogues. Dose adjustment of apricitabine does not appear to be warranted when the drug is given with trimethoprim-sulphamethoxazole.

Patients with head and neck cancer prefer individualized cognitive behavioural therapy.

Cognitive behaviour therapy (CBT) is a widely practiced and approved form of psychotherapy for many psychosocial difficulties. As the efficacy of CBT is recognized, its demand has increased and today exceeds the availability of qualified practitioners. Therefore, the effectiveness of delivering CBT using less labour-intensive modes than individualised therapy has been explored. These include group therapy, bibliotherapy and computer assisted therapy. Given the UK Government's impetus towards patient choice and involvement in the planning of healthcare, it was thought essential to ascertain the preferred delivery mode of patients with head and neck cancer for a CBT based intervention. Therefore, a small retrospective cohort (n= 28) of patients following treatment for head and neck cancer were sent postal questionnaires to ascertain their preferences on mode of CBT delivery. Simultaneously, the views of accredited cognitive behaviour therapists (n= 14) were determined on the optimal mode of CBT delivery to these patients. Findings indicated that patients preferred the more individualized mode of CBT delivery, namely one-to-one therapy, followed closely by bibliotherapy, with group format being the least preferred option. Professionals concurred with patients, in that one-to-one interaction was considered an optimal mode of CBT delivery, but professionals considered it equal to group therapy.

Beta-defensin evolution: selection complexity and clues for residues of functional importance.

We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mammals. For the first time, these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as in the ancient past. We have used a combination of maximum-likelihood-based tests and a maximum-parsimony-based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. During the divergence of primates, however, variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes of both negative and, more rarely, positive selection. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel rodent-specific beta-defensin gene clades. Sites in the second exon have been subject to positive selection and, by implication, are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions that are predicted to be important for the function of beta-defensins.

A bioinformatic screen for novel A-I RNA editing sites reveals recoding editing in BC10.

MOTIVATION: Recent studies have demonstrated widespread adenosine-inosine RNA editing in non-coding sequence. However, the extent of editing in coding sequences has remained unknown. For many of the known sites, editing can be observed in multiple species and often occurs in well-conserved sequences. In addition, they often occur within imperfect inverted repeats and in clusters. Here we present a bioinformatic approach to identify novel sites based on these shared features. Mismatches between genomic and expressed sequences were filtered to remove the main sources of false positives, and then prioritized based on these features. This protocol is tailored to identifying specific recoding editing sites, rather than sites in non-coding repeat sequences. RESULTS: Our protocol is more sensitive for identifying known coding editing sites than any previously published mammalian screen. A novel multiply edited transcript, BC10, was identified and experimentally verified. BC10 is highly conserved across a range of metazoa and has been implicated in two forms of cancer.

Proteins containing the UBA domain are able to bind to multi-ubiquitin chains.

The UBA domain is a motif found in a variety of proteins, some of which are associated with the ubiquitin-proteasome system. We describe the isolation of a fission-yeast gene, mud1+, which encodes a UBA domain containing protein that is able to bind multi-ubiquitin chains. We show that the UBA domain is responsible for this activity. Two other proteins containing this motif, the fission-yeast homologues of Rad23 and Dsk2, are also shown to bind multi-ubiquitin chains via their UBA domains. These two proteins are implicated, along with the fission-yeast Pus1(S5a/Rpn10) subunit of the 26 S proteasome, in the recognition and turnover of substrates by this proteolytic complex.

Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorder.

We have undertaken a search for polymorphic sequence variation within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2 (DISC1 and DISC2), which are both novel genes that span a translocation breakpoint strongly associated with schizophrenia and related psychoses in a large Scottish family. A scan of the coding sequence, intron/exon boundaries, and part of the 5' and 3' untranslated regions of DISC1, plus 2.7 kb at the 3' end of DISC2, has revealed a novel microsatellite and 15 novel single nucleotide polymorphisms (SNPs). We have tracked the inheritance of four of the SNPs through multiply affected families, and carried out case-control association studies using the microsatellite and four common SNPs on populations of patients with schizophrenia or bipolar affective disorder versus normal control subjects. Neither co-segregation with disease status nor significant association was detected; however, we could not detect linkage disequilibrium between all these markers in the control population, arguing that an even greater density of informative markers is required to test rigorously for association in this genomic region.

Bases and spaces: resources on the web for accessing the draft human genome - II - after publication of the draft.

The volume of human genome sequence and the variety of web-based tools to access it continue to grow at an impressive rate, but a working knowledge of certain key resources can be sufficient to get the most from your genome. This article provides an update to Genome Biology 2000, 1(4):reviews2001.1-2001.5.

Physical mapping: integrating computational and molecular genetic data.

A crucial step beyond the identification of genetic linkage of a disease to a chromosomal region is the production of a physical map that will allow the identification of candidate genes. Although the process of physical map building has been facilitated by the flow of data released by the Human Genome Project, gathering all the information together requires significant effort. In a previous study, we reported linkage between Bipolar Affective Disorder and the chromosomal location 4p15.3--p16.1. In this review we use this example to describe how to collect publicly available sequence, DNA fingerprint, and genetic marker data and integrate these with empirical data to build a large scale high resolution physical map of a region. Methods used to identify new genetic markers and candidate genes within a circumscribed region are also presented.