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.

Differential impact of COVID-19 on mental health and burnout.

BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.

Repurposing Zidovudine in combination with Tigecycline for treating carbapenem-resistant Enterobacteriaceae infections.

The global emergence of carbapenem-resistant Enterobacteriaceae (CRE) presents a significant clinical concern, prompting the WHO to prioritize CRE as a top priority pathogen in their 2017 global antibiotic-resistant bacteria priority list. Due to the fast-depleting antibiotic arsenal, clinicians are now resorting to using once-abandoned, highly toxic antibiotics such as the polymyxins and aminoglycosides, creating an urgent need for new antibiotics. Drug repurposing, the application of an approved drug for a new therapeutic indication, is deemed a plausible solution to this problem. A total of 1,163 FDA-approved drugs were screened for activity against a clinical carbapenem- and multidrug-resistant E. coli isolate using a single-point 10 µM assay. Hit compounds were then assessed for their suitability for repurposing. The lead candidate was then tested against a panel of clinical CREs, a bactericidal/static determination assay, a time-kill assay and a checkerboard assay to evaluate its suitability for use in combination with Tigecycline against CRE infections. Three drugs were identified. The lead candidate was determined to be Zidovudine (azidothymidine/AZT), an oral anti-viral drug used for HIV treatment. Zidovudine was shown to be the most promising candidate for use in combination with Tigecycline to treat systemic CRE infections. Further experiments should involve the use of animal infection models.

Study protocol on comparative effectiveness of mindfulness meditation and qigong on psychophysiological outcomes for patients with colorectal cancer: a randomized controlled trial.

BACKGROUND: Colorectal cancer imposes threats to patients' well-being. Although most physical symptoms can be managed by medication, psychosocial stressors may complicate survival and hamper quality of life. Mindfulness and Qigong, two kinds of mind-body exercise rooted in Eastern health philosophy, has been found effective in symptoms management, improving mental health, and reducing stress. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the comparative effectiveness of mindfulness and Baduanjin intervention on the bio-psychosocial wellbeing of people with colorectal cancer. METHODS/ DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred eighty-nine participants will be randomized into (i) Mindfulness, (ii) Baduanjin, or (iii) waitlist control groups. Participants in both the Baduanjin and mindfulness groups will receive 8-weeks of specific intervention. All three groups will undergo four assessment phases: (i) at baseline, (ii) at 4-week, (iii) at 8-week (post-intervention), and 6-month post-intervention (maintenance). All participants will be assessed in terms of cancer-related symptoms and symptom distress, mental health status, quality of life, stress level based on physiological marker. DISCUSSION: Based on prior research studies, participants in both the mindfulness and Baduanjn intervention group are expected to have better symptoms management, lower stress level, better mental health, and higher level of quality of life than the control group. This study contributes to better understanding on the common and unique effectiveness of mindfulness and Baduanjin qigong, as such patients and qualified healthcare professionals can select or provide practices which will produce maximum benefits, satisfaction, adherence, and sustainability. TRIAL REGISTRATION: The trial has been registered in the Clinical Trials Centre of the University of Hong Kong ( HKCTR-2198 ) on 08 March 2017.

Dimensionality of the Center for Epidemiologic Studies Depression Scale: an exploratory bi-factor analytic study.

OBJECTIVE: The Center for Epidemiologic Studies Depression Scale (CES-D) is a widely used instrument for measuring depressive symptoms. Though conventional factor analytic evaluations supported the use of four sub-scales for the CES-D, existing studies have yet to adopt the bi-factor analytic approach in psychometric assessment of the 20-item inventory. The present study aimed to apply both confirmatory factor analysis and exploratory bi-factor analysis to evaluate the dimensionality of the CES-D. METHODS: Current scoring practice of the CES-D (single-factor, four-factor, and second-order models) was tested using confirmatory factor analyses in a sample of 706 Chinese persons with insomnia and depressive symptoms. As an alternative, exploratory bi-factor analysis was conducted to examine the utility of the general depression factor and specific factors. RESULTS: Existing measurement models on the CES-D did not provide an adequate model fit to the data in terms of model fit indices and discriminant validity. The bi-factor model revealed a general depression factor that accounted for the majority of the item variance. The three specific factors (somatic symptoms, positive affect, and interpersonal problems) provided little unique information over and above the general factor and plausibly represent a methodological artifact rather than a substantive factor. CONCLUSION: The present study demonstrated empirical support for the bi-factor model as a realistic representation of the underlying structure of the CES-D. Researchers and clinicians are better served by simply using a single measure of depression.

The relationships of change in work climate with changes in burnout and depression: a 2-year longitudinal study of Chinese mental health care workers.

Mental health care workers face heavy emotional demand and are prone to work burnout. Work burnout has been associated with poor mental health and work climate, which refers to individual perceptions about work setting. The purpose of this study was to examine whether intra-individual changes in work climate were associated with intra-individual changes in burnout and depression over two years. The present sample included Chinese mental health care workers (N = 312; mean age = 38.6, SD = 9.9) working in a psychosocial rehabilitation institution. The participants completed questionnaires on work climate, work burnout and depression at seven time points across two years. Parallel process latent growth modeling was used to analyze the associations of change between work climate and burnout and depression. Work climate displayed a logarithmic decreasing trend while burnout and depression displayed logarithmic increasing trends over two years. Baseline levels of work climate were negatively and moderately associated with baseline levels of burnout and depression (r = -.44 to -.60, p < .01). Changes in work climate were negatively and moderately associated with change in burnout (r = -.43, p < .01) and change in depression (r = -.31, p < .05). Change in burnout was positively and strongly associated (r = .58, p < .01) with change in depression. The current results support temporal relationships among changes in work climate, burnout and depression across time. Practical implications for future preventive work in burnout interventions were discussed within this population.

The effectiveness of psychoeducational family intervention for patients with schizophrenia in a 14-year follow-up study in a Chinese rural area.

BACKGROUND: It is unclear if the impact of psychoeducational family intervention for patients with schizophrenia can be sustained over 10 years. In this study, we explored the 14-year effect of psychoeducational family intervention for patients with schizophrenia in a Chinese rural area. METHOD: The data from a cluster randomized control trial (CRCT) study of psychoeducational family intervention in a 14-year follow-up was analyzed. All patients with schizophrenia (n = 326) who participated in the CRCT drawn from six townships in Xinjin County of Chengdu in 1994, of whom 238 (73.0%) who were still alive, and their informants were followed up in 2008. The Patients Follow-up Scale, the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning were used in the follow-up study. RESULTS: There were no significant differences of marital status, mean scores of PANSS positive symptoms, negative symptoms, general mental health, and total scores among the psychoeducational family intervention, medication, and control groups in 2008. The psychoeducational family intervention group had a significantly higher rate of antipsychotic medication and a higher level of work ability than other two groups. The control group had a significantly higher rate of never-treated (26.0%) than psychoeducational family intervention group (6.5%). CONCLUSION: Psychoeducational family intervention might be still effective in the 14-year follow-up, especially in patients' treatment adherence/compliance and social functioning. Psychoeducational family intervention might be more effective in places where family members frequently participated in patients' care and had a lower level of knowledge on mental illness. Family intervention should be considered when making mental health policy and planning mental health services.

Psychometric properties of the Chalder Fatigue Scale revisited: an exploratory structural equation modeling approach.

OBJECTIVE: Previous validation studies of the Chalder Fatigue Scale (CFS) suffer methodological shortcomings. The present study aimed to re-evaluate its psychometric properties using exploratory structural equation modeling (ESEM). METHODS: A Chinese sample of 1259 community-dwelling residents completed the 11-item Chinese CFS and a variety of health measures (anxiety, depression, exhaustion, sleep disturbance, and quality of life). In addition to traditional confirmatory factor analysis, ESEM was performed to assess the fit of two- and three-factor models using robust maximum likelihood estimation and oblique geomin rotation. Convergent validity of the CFS was examined via associations with five covariates (gender, age, exercise, perceived health, and life event) and the health measures in the ESEM model. RESULTS: The ESEM models displayed a superior fit to confirmatory factor models. The three-factor ESEM model showed a satisfactory model fit to the data but not for the two-factor model. The three factors were physical fatigue (three items, α = .800), low energy (four items, α = .821), and mental fatigue (four items, α = .861). The factors exhibited convergent validity with the model covariates and health measures. CONCLUSION: The results demonstrate the satisfactory reliability and convergent validity for the three-factor structure of the CFS as a valid measure of fatigue symptoms in the general population. Future psychometric studies could adopt the ESEM approach as a practical alternative to traditional confirmatory factor analysis.

Annual review of children with tuberous sclerosis.

Tuberous sclerosis complex is a complex childhood disorder characterised by the formation of hamartomas in multiple organs. Annual review of this disease is recommended to monitor the development of complications. We aim to provide a concise, evidence-based framework to assist clinicians during this annual review. We focus on the following areas: (A) what questions need to be asked during annual review, (B) which areas need emphasis on examination, (C) when is an investigation required and (D) referral to tertiary specialists and other members of the multidisciplinary team. It should also be noted that there are ongoing debates regarding screening intervals in certain areas. These include the frequency, modality of screening and degree of intervention for astrocytomas and renal angiomyolipomas. This review seeks to summarise the product of the ongoing debates, and provide evidence-based suggestions in light of the uncertainty.

Psychometric properties of the Copenhagen Burnout Inventory-Chinese version.

The Copenhagen Burnout Inventory is a measurement scale that assesses the degree of burnout in the personal, work, and client domains. The aim of this study was to examine the psychometric properties of the inventory's Chinese version (CBI-C) in a sample of 312 human service workers in Hong Kong with follow-up assessment for 245 participants. The results of confirmatory factor analyses show the revised three-factor model to have an adequate fit in the baseline and cross-validation samples. The CBI-C demonstrates good degrees of internal consistency, test-retest reliability, and concurrent validity, and appears to be a valid and reliable measurement tool of burnout in the Chinese context.

Extended haplotype association study in Crohn's disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3.

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare CD-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association.

Emergency versus semi-elective management of mandible fractures: a Maxillofacial Trainee Research Collaborative (MTReC) study.

INTRODUCTION: Recent evidence suggests that acute emergency management of mandible fractures does not improve surgical outcomes yet is associated with increased financial burden. Current NHS policy advocating for increased adoption of day-case and semi-elective surgical procedures to reduce bed strain must be balanced with providing timely, effective treatment. Our research aims to determine patient groups currently managed via semi-elective admission and whether this can be extended to other groups to provide safe and effective management of mandible fractures. METHODS: A multi-national trainee-led audit of mandibular fractures across 49 units was completed by the Maxillofacial Trainee Research Collaborative (MTReC). Each unit prospectively collected data on fractures on admission and at follow-up. Data collected included patient demographics, behaviour, health, injury, timing to intervention and surgical complications. RESULTS: Data were collected on 947 mandibular fractures. Of the surgically managed patients, 649 (90%) were managed via acute emergency admission at the time of presentation, while 68 (10%) were managed semi-electively. Patient demographics, injury pattern and mechanism appeared to significantly affect timing of management, whereas patient behaviour, health status, timing of injury and presentation did not. Semi-elective management was associated with a significantly shorter inpatient duration (0.9 versus 1.9 days, p=0.000) with no differences in readmission, antibiotic usage or surgical complications (p=1.000, RR 1.030). CONCLUSION: Our study demonstrates the efficacy of planned admissions and semi-elective management of mandibular fractures. Simple mandibular fractures in compliant patients are suitable for semi-elective treatment. Holistic patient assessment and tailored surgical planning is crucial in determining admission modality to effectively manage mandibular trauma.

Large-area anodized alumina nanopore arrays assisted by soft ultraviolet nanoimprint prepatterning.

Aluminium anodization under optimized conditions can naturally generate close-packed and aligned nanopore arrays, but the spatial extent of such regular pore arrangement is generally limited. Here we demonstrated the use of soft ultraviolet nanoimprint lithography to guide the formation of nanopores at specific locations, using an elastomer negative mold for the process. By anodizing at voltages which naturally led to the formation of pores with matching averaged interpore separation, pre-patterned triangular holes (diameter 100 nm, periodicity 350 nm) on aluminium thin films induced conformal growth of nanopores at pre-defined positions. In addition, pores in geometries other than close-packed patterns were prepared, with square pore arrangement being demonstrated in this work. The influence of the anodization voltage on the final pore formation was also studied. Our results illustrated the possibility to fabricate well-organized nanopore arrays with conditions far less stringent than those reported in literature, which has the potential to be adopted for applications where regular pore alignment are critical.

A practical approach to continuous glucose monitoring (rtCGM) and FreeStyle Libre systems (isCGM) in children and young people with Type 1 diabetes.

Real-time continuous glucose monitoring (rtCGM) and FreeStyle Libre glucose monitoring systems (isCGM) are new evolving technologies used in the management of Type 1 diabetes. They offer potential to improve diabetes control and reduce hypoglycaemia. rtCGM can be linked to insulin pump providing hybrid closed loop therapy. Families of children and young people are keen to have the benefit from these technologies. These are relatively expensive so it is important that health care professionals, families of children and young people (CYP) with diabetes are adequately trained in the use of these devices. Health care professionals need to be able to make patient selection based on individual needs and preferences to achieve maximum benefit. Association of Children's Diabetes Clinicians (ACDC) developed a comprehensive guideline in 2017 to help identify which patients may be most likely to benefit and how these technologies may be practically implemented. Since then new technologies have been introduced and the use of GCM has expanded in routine clinical practice. This article, aims to provide a practical approach and help identify which patients may be most likely to benefit and how the technology may be implemented in order to maximise the clinical benefits.

Study Protocol of Brief Daily Body-Mind-Spirit Practice for Sustainable Emotional Capacity and Work Engagement for Community Mental Health Workers: A Multi-Site Randomized Controlled Trial.

BACKGROUND: Given the emotional demanding nature of social services, we developed a brief daily body-mind-spirit (BMS) program and successfully piloted it with workers at elderly services. The proposed study focuses on community mental health workers who are often under chronic stress and vulnerable to burnout. METHODS: The study aims to evaluate the program for fostering sustainable emotional capacity and work engagement for community mental health workers. A multi-site randomized controlled trial design is adopted. All the 24 the Integrated Community Centre for Mental Wellness (ICCMW of Hong Kong will be approached to join this program. Assuming conservatively, 60% ICCWM (14 centers) will respond and participate. At each site, a pair of intervention and control groups will be run. The targeted total sample size is 224. To investigate the course of changes in burnout and engagement, each group will last 6 months, including 3-month intervention and 3-month follow-up. Measures will be taken at monthly intervals. DISCUSSION: In light of literature and the pilot trial's findings, participants in the Brief Daily BMS intervention group are expected to have a reduced burnout level and a narrowing of range in work engagement during the 3 months intervention. And within the 3 months post-intervention period, a rebound of burnout level and a widening of range in work engagement are expected to be observed in the same group of participants. Hopefully, this study will contribute to the deeper understanding of burnout and work engagement, and shed light on sustainable intervention for emotionally demanding workplaces. CLINICAL TRIAL REGISTRATION: The trial has been registered in the Clinical Trials Centre of the University of Hong Kong. HKUCTR-2763 Registered 27 December 2019 - Retrospectively registered, http://www.hkuctr.com/Study/Show/eb930d24e2c647afb7a922055163f24b.

A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.

AIMS: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8-10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. MATERIALS AND METHODS: This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8-10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. RESULTS: Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8-84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. CONCLUSIONS: We demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.