Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Uveal and conjunctival melanomas: disease course and outcomes in Chinese patients.

INTRODUCTION: Epidemiological studies of ocular melanomas have largely focused on Caucasian populations. This study reviewed the course and outcomes of uveal melanoma (UM) and conjunctival melanoma (CM) in Chinese patients. METHODS: This retrospective study included patients with UM and CM who received treatment in a tertiary eye centre in Hong Kong from January 1994 to December 2019. Data were recorded concerning patient demographics, tumour laterality, tumour characteristics, investigations performed, treatment regimen, and final outcomes. RESULTS: During the 25-year study period, there were 13 patients with UM and 11 patients with CM who did not display nodal or systemic involvement at diagnosis. The mean ± standard deviation ages at diagnosis of UM and CM were 59 ± 15.8 and 57 ± 13.9 years, respectively. There were more men among patients with UM than among those with CM (P=0.042). Most patients with UM underwent primary enucleation (n=12; 92.3%), whereas most patients with CM underwent orbital exenteration (n=9; 81.8%). The prognosis was significantly worse for CM than for UM. The median disease-free survival were 5.2 years (range, 0.7-20.5) and 2.1 years (range, 0.1-24.9) for UM and CM, respectively. Melanoma-related mortality was significantly higher among patients with CM than among those with UM (P=0.006). CONCLUSION: Compared with UM, CM has higher rates of systemic metastasis and tumour-related mortality in Hong Kong Chinese patients, regardless of prior definitive treatment.

Impact of COVID-19 on the sleep-wake patterns of preschool children.

OBJECTIVE: To explore the impact of the COVID-19 pandemic on the sleep-wake patterns of preschool children. METHODS: A cohort of preschoolers established before the COVID-19 pandemic was invited to participate in this study. Data including children's demographics, their own and parental sleep-wake patterns, physical activities, and screen time were collected through an online questionnaire from August to September 2020. A comparison was made on the collected data from the same cohort of children before and during the pandemic. RESULTS: The cohort which was established before the pandemic consisted of 3720 preschoolers. For this current study, 642 (17%) participated, and 497 (13%) children who fulfilled the eligibility criteria were included in the final analysis. They showed a delay in their bedtime and wake time on both weekdays and weekends with a 15-30 min increase in nocturnal sleep duration. However, with a reduction in nap time, the average daily sleep duration was shortened by 16.3 ± 64.3 min (p < 0.001) and 27.5 ± 72.9 min (p < 0.001) during weekdays and weekends, respectively. Screen time was increased while outdoor activity duration was decreased. Parental sleep/wake times were also delayed with an increase in sleep duration. Children's sleep habits were associated with screen time and parental sleep/wake patterns. CONCLUSION: Despite school suspension during the COVID-19 pandemic, preschoolers were not sleeping longer. Screen time and parental sleep/wake patterns were the major factors driving the preschoolers' sleep habits. Health education is required to control screen time in children and to promote sleep hygiene among all family members.

A general practice intervention for people at risk of poor health outcomes: the Flinders QUEST cluster randomised controlled trial and economic evaluation.

OBJECTIVE: To determine whether a multicomponent general practice intervention cost-effectively improves health outcomes and reduces health service use for patients at high risk of poor health outcomes. DESIGN, SETTING: Clustered randomised controlled trial in general practices in metropolitan Adelaide. PARTICIPANTS: Three age-based groups of patients identified by their general practitioners as being at high risk of poor health outcomes: children and young people (under 18 years), adults (18-64 years) with two or more chronic diseases, and older people (65 years or more). INTERVENTION: Enrolment of patients with a preferred GP, longer general practice appointments, and general practice follow-up within seven days of emergency department and hospital care episodes. Intervention practices received payment of $1000 per enrolled participant. MAIN OUTCOME MEASURES: Primary outcome: change in self-rated health between baseline and 12-month follow-up for control (usual care) and intervention groups. SECONDARY OUTCOMES: numbers of emergency department presentations and hospital admissions, Medicare specialist claims and Pharmaceutical Benefits Scheme (PBS) items supplied, Health Literacy Questionnaire scores, and cost-effectiveness of the intervention (based on the number of quality-adjusted life-years [QALYs] gained over 12 months, derived from EQ-5D-5L utility scores for the two adult groups). RESULTS: Twenty practices with a total of 92 GPs were recruited, and 1044 eligible patients participated. The intervention did not improve self-rated health (coefficient, -0.29; 95% CI, -2.32 to 1.73), nor did it have significant effects on the numbers of emergency department presentations (incidence rate ratio [IRR], 0.90; 95% CI, 0.69-1.17), hospital admissions (IRR, 0.90; 95% CI, 0.66-1.22), Medicare specialist claims (IRR, 1.00; 95% CI, 0.91-1.09), or PBS items supplied (IRR, 0.99; 95% CI, 0.96-1.03), nor on Health Literacy Questionnaire scores. The intervention was effective in terms of QALYs gained (v usual care: difference, 0.032 QALYs; 95% CI, 0.001-0.063), but the incremental cost-effectiveness ratio was $69 585 (95% CI, $22 968-$116 201) per QALY gained, beyond the willingness-to-pay threshold. CONCLUSIONS: Our multicomponent intervention did not improve self-rated health, health service use, or health literacy. It achieved greater improvement in quality of life than usual care, but not cost-effectively. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001589370 (prospective).

Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

BACKGROUND: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. METHODS: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. RESULTS: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. CONCLUSIONS: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

Toll-Like Receptor Responsiveness of Peripheral Blood Mononuclear Cells in Young Women with Dysmenorrhea.

PURPOSE: Dysmenorrhea is a common disorder that substantially disrupts the lives of young women. To determine whether there is evidence of activation of the innate immune system in dysmenorrhea and whether the degree of activation may be used as a biomarker for pain, we compared the responsiveness of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 2 or 4 stimulation. We also investigated whether this effect is modulated by the use of the oral contraceptive pill (OC). PATIENTS AND METHODS: Fifty-six women aged 16-35 years, with either severe or minimal dysmenorrhea, and use or non-use of the OC, were enrolled. PBMCs were collected on two occasions in a single menstrual cycle: the menstrual phase and the mid-follicular phase. PBMCs were exposed to lipopolysaccharide (LPS), a TLR4 agonist, and PAM3CSK4 (PAM), a TLR2 agonist, and the resulting interleukin-1beta (IL-1ß) output was determined. Statistical analysis compared the EC50 between groups as a measure of TLR responsiveness of PBMCs. RESULTS: The key finding following LPS stimulation was a pain effect of dysmenorrhea (p=0.042) that was independent of use or non-use of OC, and independent of day of testing. Women with dysmenorrhea showed a large 2.15-fold (95% CI -4.69, -0.09) increase in IL-1ß release when compared with pain-free participants across both days. CONCLUSION: This is the first study to demonstrate an ex vivo immune relationship in women with dysmenorrhea-related pelvic pain. It provides evidence for the potential of immune modulation as a novel pharmacological target for future drug development in the management of dysmenorrhea.

Patterns of middle-ear cholesteatoma and implications for surgical approach.

OBJECTIVES: Understanding the pattern of middle-ear cholesteatoma becomes pertinent with the rise of endoscopic surgery as surgeons decide on the optimal approach to visualise and extirpate disease. With modifications to the Telmesani attic-tympanum-mastoid staging system, this study aimed to evaluate the commonest patterns of middle-ear cholesteatoma and their implications for surgical approach. METHODS: A retrospective study was conducted in a single tertiary institution in Singapore. All patients undergoing cholesteatoma surgery between January 2012 and June 2015 were included. Staging of cholesteatoma was based on clinical assessment corroborated by radiological findings. RESULTS: Out of the 55 ears included, 98.2 per cent had cholesteatoma involving the attic. The disease extended into the mastoid antrum and beyond in 43 cases (78.2 per cent). The facial recess and/or sinus tympanum was affected in 26 cases (47.3 per cent). CONCLUSION: The majority of cholesteatoma cases present with extensive attic disease and significant mastoid involvement. In these cases, endoscopes may be best suited to adjunctive rather than exclusive use in surgery.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

Sentinel lymph node biopsy for melanoma of the head and neck: a multicentre study to examine safety, efficacy, and prognostic value.

Sentinel lymph node biopsy (SLNB) is an accurate staging procedure for malignant melanoma but its use in patients with melanoma of the head and neck has been questioned in the past because of a perceived record of poor safety and accuracy. Technical improvements have sought to redress this. Vital structures and variable lymphatic pathways can make its use in the head and neck challenging. In our study we have examined the data and the experiences of clinicians from University Hospital Southampton and the Royal Surrey County Hospital. We retrospectively analysed the data and case notes of 143 patients who had SLNB to establish its safety, efficacy, and prognostic value. The detection rate of at least one sentinel lymph node was 100%. Nodes positive for metastatic melanoma were found in 20% of patients. Of them, 76% went on to have completion lymphadenectomy. Multivariate Cox regression analysis suggested that positive SLNB was a strong predictor of reduced overall survival for all Breslow-thickness melanomas (HR=3.9, p=0.019) and intermediate melanomas (HR=6.3, p=0.007). It predicted reduced recurrence-free survival for all melanomas (HR=7.4, p<0.001) and was a strong predictor for those of intermediate thickness (HR=8.3, p<0.001). The false negative rate was 9.4% and false omission rate 2.6%. Temporary and permanent morbidity rates were 2.1% and 0%, respectively. SLNB for melanoma in the head and neck is a safe, accurate staging procedure that offers prognostically useful information. The upstaging of disease allows access to trial-based targeted treatments.

Optics of Perovskite Solar Cell Front Contacts.

The front contact has a major impact on the electrical and optical properties of perovskite solar cells. The front contact is part of the junction of the solar cell and must provide lateral charge transport to the terminals and should allow for an efficient light incoupling, while having low optical losses. The complex requirements of the perovskite solar front contact will be described and the optics of the front contact will be investigated. It will be shown that the front contact has a distinct influence on the short-circuit current and energy conversion efficiency. Metal oxide films were investigated as potential front contacts. The incoupling of light in the solar cell is investigated by three-dimensional finite-difference time-domain optical simulations and optical measurements of experimentally realized self-textured zinc oxide films. The zinc oxide films were prepared by metal-organic chemical vapor deposition at low temperatures. Furthermore, the influence of free carrier absorption of metal oxide films on the optics of low bandgap and/or tandem solar cells is investigated. Guidelines are provided on how to choose the doping concentration and thickness of the metal oxide films. Finally, it will be shown that by selecting an optimal front contact design the short-circuit current and energy conversion efficiency can be increased by at least 15%.

Update on the association between dry eye disease and meibomian gland dysfunction.

Dry eye disease is one of the most common ophthalmic complaints; it results from the activity of various pathways and is considered a multifactorial disease. An important factor that contributes to the onset of dry eye disease is meibomian gland dysfunction. Meibomian gland dysfunction causes a disruption in the tear film lipid layer which affects the rate of tear evaporation. This evaporation leads to tear hyperosmolarity, eventually triggering the onset of dry eye disease. Dry eye disease and meibomian gland dysfunction are strongly associated with each other, such that many of their risk factors, signs, and symptoms overlap. This review aimed to provide an update on the association between dry eye disease and meibomian gland dysfunction. A stepwise approach for diagnosis and management is summarised.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Incidental mastoiditis on magnetic resonance imaging scans: clinical relevance and cost implications.

OBJECTIVES: To determine: (1) the incidence of incidental 'mastoiditis' reported on magnetic resonance imaging scans performed in patients with asymmetrical sensorineural hearing loss and/or unilateral tinnitus; (2) how many of those patients have actual otological pathology and/or require treatment; and (3) the financial implications of such a reporting practice. METHOD: Retrospective case series. RESULTS: Between October 2015 and November 2016, 500 patients underwent magnetic resonance imaging of the internal auditory meatus to rule out cerebellopontine angle lesions. There was an incidental finding of increased mastoid signalling in 5.8 per cent (n = 29), of which 20.7 per cent (6 of 29) were reported as bilateral cases. The diagnosis of 'mastoiditis' was found in 39.7 per cent (29 of 73). None of these patients had any pathology identified clinically. Other significant pathology was identified in a further 8.8 per cent (n = 44). CONCLUSION: The diagnosis of mastoiditis is primarily clinical. An incidental finding of high signalling in the mastoid region on magnetic resonance imaging is highly unlikely to represent actual clinical disease. In patients who are scanned for other reasons and who do not complain of otological symptoms, such findings are unlikely to require otolaryngology input.

Dislocation of cochlear implant magnet during 1.5 Tesla magnetic resonance imaging despite head bandaging, and its repositioning using an endoscopic approach.

BACKGROUND: Dislocation of the cochlear implant magnet is an uncommon but recognised complication of magnetic resonance imaging in a patient with a cochlear implant.Case reportThis paper reports a case of cochlear implant magnet dislocation despite head bandaging. The patient subsequently underwent endoscopic repositioning of the magnet under general anaesthesia. The cochlear implant system was tested intra-operatively and confirmed to be functioning. The patient was well at follow up and the small wound healed well with no complications. CONCLUSION: This report presents the endoscopic technique as a viable minimally invasive surgical approach to address cochlear implant magnet dislocation.

NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.