Sacroiliitis in inflammatory bowel disease on abdominal computed tomography: prevalence, misses, and associated factors.

OBJECTIVE: To evaluate the prevalence and rate of a missed diagnosis of sacroiliitis on abdominal computed tomography (CT) in patients with inflammatory bowel disease (IBD). Factors associated with sacroiliitis were also assessed. METHOD: This retrospective study included 210 patients with IBD (mean age 31.1 years) who underwent abdominal CT. Based on a validated abdominal CT scoring tool, bilateral sacroiliac (SI) joints on abdominal CT in the whole study population were retrospectively reviewed. Subsequently, patients were classified into the 'patients with sacroiliitis' group and the 'patients without sacroiliitis' group. Univariate and multivariate regression analyses were used to clarify the factors associated with sacroiliitis. RESULTS: Sacroiliitis was identified in 26 out of 210 patients (12.4%). However, sacroiliitis was recognized on the primary reading in only five of these 26 patients (19.2%) and was missed on the initial report in the remaining 21 patients (80.8%). Among the 21 patients, 20 (95.2%) were finally diagnosed with axial spondyloarthritis (axSpA). There was a higher prevalence of female sex (p = 0.04), upper gastrointestinal involvement (p = 0.04), and back pain (p < 0.01) in patients with sacroiliitis than in those without sacroiliitis. However, on multivariate analysis, back pain was the only factor associated with sacroiliitis (p = 0.01). CONCLUSION: Physicians should carefully evaluate SI joints on abdominal CT in patients with IBD to enable early detection of sacroiliitis, potentially leading to an early diagnosis of axSpA. In addition, if patients with IBD present with back pain, the possibility of sacroiliitis should be considered.

Long-term survival in patients with brain-only metastatic non-small cell lung cancer undergoing upfront intracranial stereotactic radiosurgery and definitive treatment to the thoracic primary site.

BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared. RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death. CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.

Valence state switching and reversible emission tunability of A2SiO4 (A = Ba, Sr, and Ca) with two-site substitution of Eu ions through simple thermal treatment.

We investigated the changes in the structural and luminescent properties of Eu-ion-doped A2SiO4 (A2SiO4:Eu, A = Ba, Sr, and Ca) by annealing in oxidizing and reducing atmospheres. The initially synthesized samples displayed distinct, intense red emissions at approximately 600 and 700 nm, which can be attributed to the presence of Eu3+ ions. The emission intensity of Eu3+ was the strongest in Ca2SiO4:Eu, which exhibited the lowest lattice symmetry among the three samples. Remarkably, following annealing in a reducing atmosphere (H2), the previously observed red emission vanished, and instead, a strong green emission at around 500 nm, which is characteristic of Eu2+ ions. Because of the two occupation sites of the Eu ions in A2SiO4, the emission of Eu2+ strongly depends on the excitation wavelength, which is the most evident in Ca2SiO4:Eu. Conversely, after annealing in an oxidizing atmosphere (O2), the emission in the green region was suppressed and the emission in the red region returned. The reversible transition between two oxidation states occurred repeatedly by alternating H2 and O2 annealing, resulting in good color tunability in wide visible region with a simple ambient annealing process in a single compound.

A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Use of computed tomography sinography for evaluation of draining tracts in 27 dogs and one cat.

OBJECTIVES: To describe the clinical findings, imaging findings and outcome in patients in which CT sinography was performed, and assess to what degree this technique adds information about the extent of a tract or increases the accuracy of diagnosis of foreign bodies on CT. MATERIALS AND METHODS: Retrospective review of medical records of 27 dogs and one cat with draining tracts that had CT sinography. Pre- and post-intravenous (IV) contrast CT series were compared with CT sinography in each patient. RESULTS: Median duration of clinical signs before referral was 85 days (range 2 to 1478 days). The most common reported clinical signs were swelling (14/28, 50%) and regional pain (5/28, 18%). CT sinography revealed a more extensive tract than post-IV contrast CT in 21% cases. On post-IV contrast CT, 31% of foreign bodies were detected compared to 23% on CT sinography. All four foreign bodies detected by CT were observed in the non-contrast images. Surgery was performed after CT in 22 (79%) cases. Thirteen (46%) draining tracts resolved after surgery, three (11%) resolved without surgery, six (21%) persisted or recurred after surgery, and six (21%) were lost to follow-up. CLINICAL SIGNIFICANCE: CT sinography provides limited additional information about the extent of draining tracts compared to pre- and post-IV contrast CT images and did not increase the number of foreign bodies identified.

Multi-chord IR-visible two-color interferometer on KSTAR.

Major parts of an IR-visible two-color interferometer (TCI) on KSTAR have been upgraded for the multi-chord operation: (1) a diode-pumped-solid-state (DPSS) laser (660 nm) replacing the former HeNe laser (633 nm), (2) vacuum-compatible vibration isolator with titanium retro-reflectors, and (3) full digital phase comparator for multi-chord real-time density signals. The commercial compact DPSS laser suits the multiple chord configuration with its strong beam power (500 mW) and long coherent length (>100 m). Ti retro-reflectors are mounted on vacuum-compatible vibration isolators. The isolators are essential for the visible beams to avoid any fringe skips due to their short wavelength, considering the speed of the mechanical vibration (up to hundreds of µm). Field-programmable-gate-array (FPGA) modules count the entire fringes fast enough with a signal output rate up to 1.25 MHz, solving the fringe skip issues. The FPGA module enables the full digital processing of the phase comparator with a CORDIC algorithm after the sampling rate of 160 MS/s for the 40 MHz intermediate frequency of each beam. The full digital signals are transferred to the main plasma control system in real-time. Stable single-input-single-output operation of the KSTAR density control was demonstrated with the TCI. The real-time density profile control is also promising in the near future, with multiple actuators such as pellets and gas puffings.

Development of a forward model for Bayesian analysis of a single crystal dispersion interferometer.

The Single Crystal Dispersion Interferometer (SCDI) is a newly developed dispersion interferometer (DI) system installed on KSTAR and has obtained the first data successfully in January 2020. Unlike conventional heterodyne DI systems, which use two nonlinear crystals, only one nonlinear crystal is used to eliminate the difficulty in overlapping the first and second harmonic beams, aligning and focusing the beams to a small aperture of the second nonlinear crystal, and resolving a problem of significant efforts to maintain the beam alignment to the second nonlinear crystal after a long beam transmission. The second nonlinear crystal is replaced by a frequency doubler, a simple electronic component. To infer a line integrated electron density with its associated uncertainty consistent with the measured data, we develop a forward model of the KSTAR SCDI that can be used as a likelihood within a Bayesian-based data analysis routine. The forward model consists of two main parts, which are an optical system and an electronics system, and it takes into account noises by modeling the mechanical vibrations and the electronic noises as Gaussian distributions, while the photon noise is modeled with a Poisson distribution. The developed forward model can be used for designing and improving the SCDI system.

The new single crystal dispersion interferometer installed on KSTAR and its first measurement.

Dispersion interferometers have been used to measure line integrated electron densities from many fusion devices. To optically suppress noise due to mechanical vibrations, a conventional dispersion interferometer typically uses two nonlinear crystals located before and after the plasma along the laser beam path. Due to the long beam path, it can be difficult to overlap the fundamental and second harmonic laser beams for a heterodyne dispersion interferometer and to focus the beams on the second nonlinear crystal located after the plasma, especially when the aperture of the nonlinear crystal is small, i.e., of the order of mm. To overcome such difficulties, a new concept of a heterodyne dispersion interferometer, a single crystal dispersion interferometer (SCDI), is developed and installed on KSTAR with the laser wavelength of 1064 nm. The concept and the optical setup of the KSTAR SCDI are discussed, as well as its first measurement during a shattered pellet injection that produces abrupt and large changes in the electron density. To demonstrate feasibility, the KSTAR SCDI measurements are also compared with those from the existing two-color interferometer.

Prognostic factors analysis for oral cavity cancer survival in the Netherlands and Taiwan using a privacy-preserving federated infrastructure.

The difference in incidence of oral cavity cancer (OCC) between Taiwan and the Netherlands is striking. Different risk factors and treatment expertise may result in survival differences between the two countries. However due to regulatory restrictions, patient-level analyses of combined data from the Netherlands and Taiwan are infeasible. We implemented a software infrastructure for federated analyses on data from multiple organisations. We included 41,633‬ patients with single-tumour OCC between 2004 and 2016, undergoing surgery, from the Taiwan Cancer Registry and Netherlands Cancer Registry. Federated Cox Proportional Hazard was used to analyse associations between patient and tumour characteristics, country, treatment and hospital volume with survival. Five factors showed differential effects on survival of OCC patients in the Netherlands and Taiwan: age at diagnosis, stage, grade, treatment and hospital volume. The risk of death for OCC patients younger than 60 years, with advanced stage, higher grade or receiving adjuvant therapy after surgery was lower in the Netherlands than in Taiwan; but patients older than 70 years, with early stage, lower grade and receiving surgery alone in the Netherlands were at higher risk of death than those in Taiwan. The mortality risk of OCC in Taiwanese patients treated in hospitals with higher hospital volume (≥ 50 surgeries per year) was lower than in Dutch patients. We conducted analyses without exchanging patient-level information, overcoming barriers for sharing privacy sensitive information. The outcomes of patients treated in the Netherlands and Taiwan were slightly different after controlling for other prognostic factors.

PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients.

BACKGROUND: The most common dementia worldwide, Alzheimer's disease is often diagnosed via biomarkers in cerebrospinal fluid, including reduced levels of Aß1-42, and increases in total tau and phosphorylated tau-181. Here we describe results of a Phase 2a study of a promising new drug candidate that significantly reversed all measured biomarkers of Alzheimer's disease, neurodegeneration and neuroinflammation. PTI-125 is an oral small molecule drug candidate that binds and reverses an altered conformation of the scaffolding protein filamin A found in Alzheimer's disease brain. Altered filamin A links to the α7-nicotinic acetylcholine receptor to allow Aß42's toxic signaling through this receptor to hyperphosphorylate tau. Altered filamin A also links to toll-like receptor 4 to enable Aß-induced persistent activation of this receptor and inflammatory cytokine release. Restoring the native shape of filamin A prevents or reverses filamin A's linkages to the α7-nicotinic acetylcholine receptor and toll-like receptor 4, thereby blocking Aß42's activation of these receptors. The result is reduced tau hyperphosphorylation and neuroinflammation, with multiple functional improvements demonstrated in transgenic mice and postmortem Alzheimer's disease brain. OBJECTIVES: Safety, pharmacokinetics, and cerebrospinal fluid and plasma biomarkers were assessed following treatment with PTI-125 for 28 days. Target engagement and mechanism of action were assessed in patient lymphocytes by measuring 1) the reversal of filamin A's altered conformation, 2) linkages of filamin A with α7-nicotinic acetylcholine receptor or toll-like receptor 4, and 3) levels of Aß42 bound to α7-nicotinic acetylcholine receptor or CD14, the co-receptor for toll-like receptor 4. DESIGN: This was a first-in-patient, open-label Phase 2a safety, pharmacokinetics and biomarker study. SETTING: Five clinical trial sites in the U.S. under an Investigational New Drug application. PARTICIPANTS: This study included 13 mild-to-moderate Alzheimer's disease patients, age 50-85, Mini Mental State Exam ≥16 and ≤24 with a cerebrospinal fluid total tau/Aß42 ratio ≥0.30. INTERVENTION: PTI-125 oral tablets (100 mg) were administered twice daily for 28 consecutive days. MEASUREMENTS: Safety was assessed by electrocardiograms, clinical laboratory analyses and adverse event monitoring. Plasma levels of PTI-125 were measured in blood samples taken over 12 h after the first and last doses; cerebrospinal fluid levels were measured after the last dose. Commercial enzyme linked immunosorbent assays assessed levels of biomarkers of Alzheimer's disease in cerebrospinal fluid and plasma before and after treatment with PTI-125. The study measured biomarkers of pathology (pT181 tau, total tau and Aß42), neurodegeneration (neurofilament light chain and neurogranin) and neuroinflammation (YKL-40, interleukin-6, interleukin-1ß and tumor necrosis factor α). Plasma levels of phosphorylated and nitrated tau were assessed by immunoprecipitation of tau followed by immunoblotting of three different phospho-epitopes elevated in AD (pT181-tau, pS202-tau and pT231-tau) and nY29-tau. Changes in conformation of filamin A in lymphocytes were measured by isoelectric focusing point. Filamin A linkages to α7-nicotinic acetylcholine receptor and toll-like receptor 4 were assessed by immunoblot detection of α7-nicotinic acetylcholine receptor and toll-like receptor 4 in anti-filamin A immunoprecipitates from lymphocytes. Aß42 complexed with α7-nicotinic acetylcholine receptor or CD14 in lymphocytes was also measured by co-immunoprecipitation. The trial did not measure cognition. RESULTS: Consistent with the drug's mechanism of action and preclinical data, PTI-125 reduced cerebrospinal fluid biomarkers of Alzheimer's disease pathology, neurodegeneration and neuroinflammation from baseline to Day 28. All patients showed a biomarker response to PTI-125. Total tau, neurogranin, and neurofilament light chain decreased by 20%, 32% and 22%, respectively. Phospho-tau (pT181) decreased 34%, evidence that PTI-125 suppresses tau hyperphosphorylation induced by Aß42's signaling through α7-nicotinic acetylcholine receptor. Cerebrospinal fluid biomarkers of neuroinflammation (YKL-40 and inflammatory cytokines) decreased by 5-14%. Biomarker effects were similar in plasma. Aß42 increased slightly - a desirable result because low Aß42 indicates Alzheimer's disease. This increase is consistent with PTI-125's 1,000-fold reduction of Aß42's femtomolar binding affinity to α7-nicotinic acetylcholine receptor. Biomarker reductions were at least p ≤ 0.001 by paired t test. Target engagement was shown in lymphocytes by a shift in filamin A's conformation from aberrant to native: 93% was aberrant on Day 1 vs. 40% on Day 28. As a result, filamin A linkages with α7-nicotinic acetylcholine receptor and toll-like receptor 4, and Aß42 complexes with α7-nicotinic acetylcholine receptor and CD14, were all significantly reduced by PTI-125. PTI-125 was safe and well-tolerated in all patients. Plasma half-life was 4.5 h and approximately 30% drug accumulation was observed on Day 28 vs. Day 1. CONCLUSIONS: PTI-125 significantly reduced biomarkers of Alzheimer's disease pathology, neurodegeneration, and neuroinflammation in both cerebrospinal fluid and plasma. All patients responded to treatment. The magnitude and consistency of reductions in established, objective biomarkers imply that PTI-125 treatment counteracted disease processes and reduced the rate of neurodegeneration. Based on encouraging biomarker data and safety profile, approximately 60 patients with mild-to-moderate AD are currently being enrolled in a Phase 2b randomized, placebo-controlled confirmatory study to assess the safety, tolerability and efficacy of PTI-125.

Rheumatoid factor and immunoglobulin M mark hepatitis C-associated mixed cryoglobulinaemia: an 8-year prospective study.

OBJECTIVES: The prevalence and factors of hepatitis C virus (HCV) -associated mixed cryoglobulinaemia in Asia remain elusive, and we aimed to investigate these topics. METHODS: An 8-year prospective cohort study was conducted in 678 consecutive Taiwanese individuals with chronic HCV infection (438 completed an anti-HCV therapy course). RESULTS: Of 678 individuals, 437 (64.5%) had mixed cryoglobulinaemia and 20 (2.9%) had mixed cryoglobulinaemic syndrome. At baseline, IgM (cut-off >122 mg/dL), triglycerides and IgG levels, and HCV genotype 3 were independently associated with mixed cryoglobulinaemia. Rheumatoid factor (RF) levels were associated with mixed cryoglobulinaemic syndrome (cut-off >12.2 IU/mL). At 24 weeks post-therapy, the 362 individuals with a sustained virological response (SVR) had higher cured (106/362 (29.3%) versus 10/76 (13.2%), p = 0.003) and lower persistent (100/362 (27.6%) versus 33/76 (43.4%), p = 0.003) mixed cryoglobulinaemia rates than non-SVR patients. Among SVR patients, compared with baseline levels, RF, IgG and IgM levels decreased, except in individuals with new mixed cryoglobulinaemia. Pre-therapy IgM levels were associated with 24-week post-therapy new (95% CI of OR 1.002-1.023) and persistent (95% CI of OR 1.004-1.015) mixed cryoglobulinaemia in SVR patients. After up to 8 years, 24-week post-therapy IgM levels were associated with mixed cryoglobulinaemia in SVR patients (9/51; 17.64%; 95% CI of HR 1.004-1.011). Among 17 SVR patients with pre-therapy mixed cryoglobulinaemic syndrome, 5 (29.4%) had long-term mixed cryoglobulinaemia and 4 (23.5%) had mixed cryoglobulinaemic syndrome. CONCLUSIONS: Over 60% of chronic HCV-infected individuals had mixed cryoglobulinaemia, and 17.64% of SVR patients had mixed cryoglobulinaemia 8 years post-therapy. Pre-therapy RF and IgM levels marked HCV-associated mixed cryoglobulinaemic syndrome and mixed cryoglobulinaemia, respectively.

A review of the NG17 recommendations for the use of basal insulin in type 1 diabetes.

AIMS: To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes). METHODS: We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily. RESULTS: The absolute changes in HbA1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice-daily centred post hoc analysis, the 95% credible intervals for change in HbA1c crossed the line of null effect for all basal therapies, except NPH. CONCLUSIONS: In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA1c . In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations.

Burns objective scar scale (BOSS): Validation of an objective measurement devices based burn scar scale panel.

AIMS: Hypertrophic scars in burn survivors are a major cause of morbidity but the development of evidence based treatments is hampered by the lack of objective measurements of these scars. The objective of our study is to investigate the most accurate parameters for objective scar assessment and to create a combination score to facilitate the use of a panel of objective scar measurement tools. METHODS: Three independent assessors evaluated fifty five scar sites on fifty five burn patients with both the subjective modified Vancouver Scar Scale (mVSS) and a panel of objective measurement tools including the DSM II Colormeter, Cutometer, Dermascan high frequency ultrasound. The sensitivity and specificity of the objective scar parameters in predicting a mVSS score of 6 or more using the Receiving Operator Characteristic Area under the curve (ROC AUC) was then calculated and the most accurate parameters were combined to create an objective global scar score. RESULTS: The ROC AUC values were found to be highest for the Dermascan scar thickness (0.897), dermal intensity and intensity ratio (0.914 and 0.919), Cutometer R0 value (0.942), and R0 ratio (0.944). For colour measurements, ratios of scar to normal skin performed better than the single parameters for both erythema and pigmentation measurements: DSM II Erythema ratio vs Erythema (0.885 vs 0.818), DSM II a* ratio vs a* (0.848 vs 0.741); DSM II Melanin ratio vs Melanin (0.854 vs 0.761), DSM II L* ratio vs L* (0.862 vs 0.767). Analysis of the ROC AUC with chi-square test values showed that the highest AUC (0.786) was obtained with the combination of the Cutometer R0, Dermascan scar thickness, intensity and their respective scar to normal skin ratios. A total score of 5 and above (out of 6 parameters) had the highest combined sensitivity (69.0%) and specificity (83.3%). CONCLUSION: The objective parameters for the DSM II Colormeter, Cutometer and Dermascan high frequency ultrasound were all found to have moderate to strong ROC AUC values and combination of the Cutometer R0 and Dermascan scar thickness and intensity values can be used to create an objective global scar scale that can accurately differentiate patients with hypertrophic burn scarring from non-hypertrophic scars or normal skin.

Piloting a partially self-financed mode of human immunodeficiency virus pre-exposure prophylaxis delivery for men who have sex with men in Hong Kong.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg is a proven strategy for preventing human immunodeficiency virus (HIV) transmission in men who have sex with men (MSM). This study aimed to test the feasibility and acceptability of PrEP delivered at a pilot clinic for MSM in Hong Kong, where PrEP service is currently unavailable. METHODS: Partially self-financed PrEP was provided to HIV-negative adult MSM with high behavioural risk of HIV transmission after excluding hepatitis B infection and renal insufficiency. Participants received daily TDF/FTC for 30 weeks at 13.3% of the drug cost. Adherence and behaviours were monitored through questionnaires while creatinine and HIV/STI (sexually transmitted infection) incidence were monitored with point-of-care and laboratory tests. Preference for continuing with PrEP was evaluated at the end of the prescription period. RESULTS: Seventy-one PrEP-naïve MSM were included in the study, of whom 57 (80%) were retained at the end of 28 weeks. Satisfactory adherence and self-limiting adverse events were reported, while none of the participants contracted HIV. Risk compensation was observed, with an STI incidence of 3.17 per 100 person-years. At the end of the prescription period, a majority (89%) indicated interest in continuing with PrEP. Preference for PrEP was associated with age ≥28 years and peer influence (P=0.04), while stigma was a concern. Price was a deterrent to self-financed PrEP, and only half (51%) considered a monthly cost of ≤HK$500 (US$1=HK$7.8) as reasonable. CONCLUSIONS: A partially self-financed mode of PrEP delivery is feasible with good retention in MSM in Hong Kong.

Investigating the intra- and inter-rater reliability of a panel of subjective and objective burn scar measurement tools.

BACKGROUND: Research into the treatment of hypertrophic burn scar is hampered by the variability and subjectivity of existing outcome measures. This study aims to measure the inter- and intra-rater reliability of a panel of subjective and objective burn scar measurement tools. METHODS: Three independent assessors evaluated 55 scar and normal skin sites using subjective (modified Vancouver Scar Scale [mVSS] & Patient and Observer Scar Assessment Scale [POSAS]) and objective tools. The intra-class correlation coefficient was utilised to measure reliability (acceptable when >0.70). Patient satisfaction with the different tools and scar parameter importance were assessed via questionnaires. RESULTS: The inter-rater reliabilities of the mVSS and POSAS were below the acceptable limit. For erythema and pigmentation, all of the Scanoskin and DSM II measures (except the b* value) had acceptable to excellent intra and inter-rater reliability. The Dermascan ultrasound (dermal thickness, intensity) had excellent intra- and inter-rater reliability (>0.90). The Cutometer R0 (firmness) had acceptable reliability but not R2 (gross elasticity). All objective measurement tools had good overall satisfaction scores. Patients rated scar related pain and itch as more important compared to appearance although this finding was not sustained when corrected for multiple comparisons. CONCLUSION: The objective scar measures demonstrated acceptable to excellent intra- and inter-rater reliability and performed better than the subjective scar scales.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

A multicentre, UK, retrospective, observational study to assess the effectiveness of insulin glargine 300 units/ml in treating people with Type 1 diabetes mellitus in routine clinical practice (SPARTA).

AIM: To conduct an open-label study to provide UK real-world evidence regarding the use of insulin glargine 300 units/ml (U300) in people with Type 1 diabetes mellitus. METHODS: People with Type 1 diabetes who had been prescribed U300 ≥6 months before data collection and had HbA1c levels recorded within 3 months prior to U300 (baseline) were included. The primary endpoint was change in HbA1c from baseline to month 6 after U300 initiation. Other endpoints included number of documented hypoglycaemic and diabetic ketoacidosis episodes, and change in daily basal insulin dose. RESULTS: A total of 298 people with Type 1 diabetes were included [mean age 42.1 years, mean HbA1c 79 mmol/mol (9.4%)]. After U300 initiation, the mean reduction in HbA1c from baseline to month 6 was -4 mmol/mol (-0.4%; P<0.001; n=188). The total daily basal insulin dose at 6 months was 1.3 units higher than at the time of U300 initiation (P<0.001; n=275) but was not significantly different from the prior basal insulin dose. There was no clinically significant difference in weight between baseline and month 6 [mean difference +0.7 kg, 95% CI -0.1, 1.5; P=0.084; n=115). During the 6 months before and after U300 initiation, severe hypoglycaemic episodes were documented for 6/298 and 4/298 participants. Diabetic ketoacidosis episodes requiring Accident and Emergency department visits or hospitalization were documented for 4/298 and 6/298 participants, before and after U300 initiation, respectively. CONCLUSIONS: In people with Type 1 diabetes, a change in basal insulin to U300 was associated with clinically and statistically significant HbA1c improvements, without significant changes in basal insulin dose and weight. Documented severe hypoglycaemia episodes and diabetic ketoacidosis requiring Accident and Emergency department visits or hospitalization were low and similar before and after U300 initiation.

Fringe jump compensation techniques for the time-averaging zero-crossing phase measurement in the KSTAR millimeter-wave interferometer.

A fringe jump compensation algorithm has been developed for a phase measurement that measures the phase within a single fringe. The algorithm is extremely useful in the case of the time-averaging zero-crossing phase detector on noisy environments. When the noise level on the measurements is not sufficiently suppressed, the signals near the fringe jump show a negative slope instead of a sharp drop. The slope brings an ambiguity over the compensation process. An algorithm with an additional channel that measures the phase of a half fringe shift has been applied in the millimeter-wave interferometer on the Korea Superconducting Tokamak Advanced Research device. These techniques removed the ambiguity in most cases. The algorithm can provide a most simple, robust, and cost-effective solution for the phase measurement system in various fields.