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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Genetic variation for total fitness in Drosophila melanogaster.

We measured the heterozygous effects on net fitness of a sample of 12 wild-type third chromosomes in D. melanogaster. Effects on fitness were assessed by competing the wild-type chromosomes against balancer chromosomes, to prevent the production of recombinants. The measurements were carried out in the population cage environment in which the life history had been evolving, in an undisturbed population with overlapping generations, and replicated measurements were made on each chromosome to control for confounding effects such as mutation accumulation. We found significant variation among the wild type chromosomes in their additive genetic effect on net fitness. The system provides an opportunity to obtain an accurate estimate of the distribution of heterozygous effects on net fitness, the contribution of different fitness components including male mating success, and the role of intra-chromosomal epistasis in fitness variation.

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.

Audit of multiple insulin injection regimens in a large outpatient diabetic population.

One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses.

Inhibition of glucose-induced insulin secretion by calcium channel blocking drugs in-vitro but not in-vivo in the rat.

The organic calcium channel blocking drugs darodipine, nicardipine, diltiazem and verapamil inhibited glucose-induced (8.3 mmol L-1) insulin secretion by rat isolated islets in a concentration-dependent manner. The IC50 values (mumol L-1) for nicardipine, diltiazem and verapamil were 0.0025, 1.94 and 3.6, respectively. There were no significant differences between the potencies of any one drug when compared at two different glucose concentrations (27.8 and 8.3 mmol L-1). Isolated islets were also responsive to the calcium channel activating drugs BAY K 8644 and CGP 28392, which enhanced glucose-induced insulin secretion and prevented the inhibitory effect of verapamil. BAY K 8644 was more potent than CGP 28392. In the anaesthetized rat, neither verapamil (1 mg kg-1 i.v. 10 min before glucose) nor nicardipine (0.2 mg kg-1 i.v.) modified the glucose or insulin response to intravenous glucose whilst producing marked cardiovascular effects. The plasma concentrations of nicardipine (3.9 X 10(-8) M at 10 min post injection) were similar to those producing effects in-vitro whereas the plasma concentrations of verapamil (5 X 10(-7) M) were lower. It thus appears that the islet B cell calcium channel is less sensitive to calcium channel blocking drugs in-vivo than in-vitro. Moreover, in-vivo, the cardiovascular system is more sensitive to these drugs than are the islet B cells, although the potencies of the calcium channel blocking drug in isolated islets are similar to those reported for cardiac muscle and vascular smooth muscle in-vitro.

Attritional flexor tendon rupture due to a scaphoid non union imitating an anterior interosseous nerve syndrome: a case report.

A case is presented of acute loss of function of flexor pollicis longus and profundus tendon to the index finger. Although the aetiology was obscure, the acute onset suggested a mechanical cause rather than a nerve compression disorder such as anterior interosseous nerve palsy. X-rays showed an ununited scaphoid fracture related to an injury many years previously. Surgical exploration revealed attritional rupture of flexor pollicis longus and partial division of profundus tendon to index finger by a spicule of ununited scaphoid which had eroded through the volar capsule. Removal of the spicule and tenodesis of flexor pollicis longus gave a good long term result.

Tampon-associated toxic shock syndrome--a case report.

We report a case of tampon-associated toxic shock syndrome occurring in a 16-year-old girl. While this condition has been reported almost exclusively from the USA it is likely that TSS will be recognised elsewhere with increasing frequency as physicians become more aware of its existence. We consider that TSS must be considered in any hypotensive female in the reproductive age group with diarrhoeal illness.

Successful treatment of Graves disease in pregnancy with Lugol's iodine.

We report a case of Grave's disease in pregnancy complicated by intolerance of standard antithyroid drug therapy. We describe the success of prolonged use of organic iodine as a primary treatment prior to surgical intervention.

Addison's disease without pigmentation.

Four cases of Addison's disease are described in whom the diagnosis was unexpected or dangerously delayed because of the absence of pigmentation.