Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance ('clinical super response'): Week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study.

BACKGROUND: Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients with psoriasis. OBJECTIVES: Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate-to-severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data. METHODS: GUIDE is a phase IIIb randomized, double-blind, parallel-group, multicentre study of adults with moderate-to-severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4. RESULTS: In total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL-17A, IL-17F, IL-22 and ß-defensin 2 between SDD and LDD patients, or between SRe and non-SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated. CONCLUSIONS: Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Characterization of the public transit air microbiome and resistome reveals geographical specificity.

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.

Findings from the first public COVID-19 temporary test centre in Hong Kong.

INTRODUCTION: The Hospital Authority of Hong Kong Special Administrative Region established a coronavirus disease 2019 (COVID-19) temporary test centre at the AsiaWorld-Expo from March 2020 to April 2020, which allowed high-risk individuals to undergo early assessment of potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study reviewed the characteristics and outcomes of individuals who attended the centre for COVID-19 testing. METHODS: This retrospective cross-sectional study collected epidemiological and clinical data. The primary outcome was a positive or negative SARS-CoV-2 test result, according to reverse transcription polymerase chain reaction analyses of pooled nasopharyngeal and throat swabs collected at the centre. The relationships of clinical characteristics with SARS-CoV-2 positive test results were assessed by multivariable binary logistic regression. RESULTS: Of 1258 attendees included in the analysis, 86 individuals tested positive for SARS-CoV-2 infection (positivity rate=6.84%; 95% confidence interval [CI]=5.57%-8.37%). Of these 86 individuals, 40 (46.5%) were aged 15 to 24 years and 81 (94.2%) had a history of recent travel. Symptoms were reported by 86.0% and 96.3% of individuals with positive and negative test results, respectively. The clinical characteristics most strongly associated with a positive test result were anosmia (adjusted odds ratio [ORadj]=8.30; 95% CI=1.12-127.09) and fever ORadj=1.32; 95% CI=1.02-3.28). CONCLUSION: The temporary test centre successfully helped identify individuals with COVID-19 who exhibited mild disease symptoms. Healthcare providers should carefully consider the epidemiological and clinical characteristics of COVID-19 to arrange early testing to reduce community spread.

Labour analgesia: update and literature review.

Pain relief is an important component of modern obstetric care and can be produced by neuraxial, systemic, or inhalational analgesia or various physical techniques. We review the most recent evidence on the efficacy and safety of these techniques. Over the past decade, the availability of safer local anaesthetics, ultra-short acting opioids, combined spinal-epidural needles, patient-controlled analgesic devices, and ultrasound have revolutionised obstetric regional analgesia. Recent meta-analyses have supported epidural analgesia as the most efficacious technique, as it leads to higher maternal satisfaction and good maternal and fetal safety profiles. We examine the controversies and myths concerning the initiation, maintenance, and discontinuation of epidural analgesia. Recent evidence will also be reviewed to address concerns about the effects of epidural analgesia on the rates of instrumental and operative delivery, lower back pain, and breastfeeding. New developments in labour analgesia are also discussed.

Cumulative patient-based disease activity monitoring in rheumatoid arthritis - predicts sustained remission, flare and treatment escalation.

OBJECTIVE: Patient-based Disease Activity Score 2 (PDAS2) had been developed for RA patients to self-assess and record disease activity in between clinic visits. This study explored the clinical utility of time-integrated cumulative PDAS2 (cPDAS2) on predicting sustained remission or low disease activity state (LDAS), flare and treatment escalation. METHODS: We recruited 100 patients to record PDAS2 at home fortnightly between two consecutive clinic visits. Rheumatologists adjusted treatment according to disease activity recorded during clinic consultation while blinded to home PDAS2 scores. cPDAS2 calculated from the area-under-curve of all PDAS2 scores were compared with disease activities at both visits. cPDAS2 and ΔcPDAS2 (change from PDAS2 at the first visit) were tested to determine their ability to predict ACR/EULAR remission, SDAI flare-up (from remission/LDAS to moderate/high disease activity) and treatment escalation. Optimal cut-points were determined by Receiver Operator Characteristic curve. RESULTS: Mean age of the patients was 59 years, mean RA duration 14 years, 90% were female, 71% seropositive and 64% in remission/LDAS. The home PDAS2 completion rate was 92%. PDAS2 scores were done 7.5 times every 15 days over a 16-week follow-up (all medians). The sensitivity of cPDAS2 in predicting Boolean/SDAI remission at two visits, DAS28, SDAI and CDAI remission or LDAS were 93%, 84%, 73% and 80% respectively. cPDAS2 ≥ 0.29 predicted flare (P = 0.04), with specificity 79% and negative predicting value (NPV) 88%. Rheumatologists' decision to escalate treatment was predicted by (cPDAS2 ≥ 4.33 and ΔcPDAS2 ≥ 0.059) (P = 0.007) with specificity 88% and NPV 89%, and (cPDAS2 ≥ 4.33 or ΔcPDAS2 ≥ 0.059) (P = 0.02) with both sensitivity and NPV 100%. CONCLUSION: PDAS2 monitoring at home is feasible. cPDAS2 is useful to predict flare and treatment escalation.

New Service Model for Common Mental Disorders in Hong Kong: a Retrospective Outcome Study.

OBJECTIVE: To review the first 8-month outcome of the Common Mental Disorder Clinic model in Hong Kong in terms of patient exit status and improvement in depressive and anxiety symptoms. METHODS: During the first appointment, patients were interviewed by a multidisciplinary team comprising a psychiatrist, a psychiatric nurse, and an occupational therapist. A multidisciplinary case conference was conducted to discuss clinical observations, diagnosis, issues of concern, and the optimal individualised treatment plan. Low-intensity interventions by nurses and/or occupational therapists were provided, as were optional, time-limited, protocol-based interventions by clinical psychologists for those with mild to moderate depressive and anxiety symptoms. Pharmacological intervention may be used when indicated. Upon completion of the treatment plan, patients were reassessed by the treating psychiatrist. Discharge options included discharge without psychiatric follow-up, step-up to psychiatric outpatient clinics, and step-down services. The self-administered Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder 7-item scale (GAD-7) were used to assess the past 2 weeks' depressive and anxiety symptoms, respectively, at baseline and at each session. RESULTS: From July 2015 to February 2016, 1325 Chinese patients received the new service. Of them, 170 men and 363 women (mean age, 52.6 years) completed the treatment plan. After treatment, their mean PHQ-9 score decreased from 11.06 to 7.55 (p < 0.001), and the mean GAD-7 score decreased from 9.94 to 6.54 (p < 0.001). After treatment, 42.4% and 48.2% of the patients were within the normal range of PHQ-9 and GAD-7 scores, respectively, compared with 16.9% and 20.8% before treatment. The mean time to implementation of the individualised treatment plan was 82.33 days. Of the patients, 54.4% were discharged without any need for medical or psychiatric follow-up; 28% were stepped up to psychiatric outpatient clinics; and 17.3% were stepped down. The predictors of exit status were whether psychiatric medication was prescribed during initial intake (p = 0.011), whether psychiatric medication was prescribed at last follow-up (p < 0.001), the service period (p = 0.010), and the GAD-7 final score (p = 0.005). CONCLUSIONS: The first 8-month outcome of the new service model was encouraging, with shortened waiting time, reduced severity of symptoms, and better exit status (high recovery and step-down rates).

'Organic Anxiety' in a Middle-aged Man Presenting with Dyspnoea: a Case Report.

We report a case of pulmonary embolism in a patient who presented with repeated anxiety attacks and psychotic symptoms and was misdiagnosed as having withdrawal seizure or anxiety disorder not otherwise specified. This case highlighted the nonspecific clinical features of pulmonary embolism and the principles in making psychiatric diagnosis. Careful history taking, thorough physical examination, appropriate investigation, and a high index of suspicion led to the correct diagnosis. The principle of hierarchy of psychiatric diagnosis (ie, organic over non-organic) and the possibility of comorbidities should always apply.

Survey on common reference intervals for general chemistry analytes in Hong Kong.

INTRODUCTION: Reference intervals (RIs) are essential tool for proper interpretation of results. There is a global trend towards implementing common RIs to avoid confusion and enhance patient management across different laboratories. However, local practices with respect to RIs lack harmonisation. METHODS: We have conducted the first local survey regarding RIs for 14 general chemistry analytes in 10 chemical pathology laboratories that employ four different analytical platforms (Abbott Architect, Beckman Coulter AU, Roche Cobas, and Siemens Dimension EXL). Analytical bias was assessed by an inter-laboratory results comparison of external quality assurance programmes. RESULTS: Sufficient inter-laboratory and inter-platform agreement regarding the 10 analytes (albumin, alanine aminotransferase, aspartate aminotransferase, chloride, gamma-glutamyl transferase, phosphate, potassium, sodium, total protein, and urea) were demonstrated. However, the RIs were heterogeneous across all laboratories, with percentage differences of the upper RI value of up to 47% for aspartate aminotransferase (absolute difference of 16 U/L), 29% for urea (1.8 mmol/L), and 18% for potassium (0.8 mmol/L). The percentage difference between lower RI values was up to 24% for urea (0.6 mmol/L), 22% for phosphate (0.16 mmol/L), and 8% for total protein (5 g/L). The coefficients of variation of the upper RI values of potassium and sodium were 1.2 times and 1.0 times of their corresponding between-subject biological variation, respectively, representing unnecessary variations that are overlooked and unchecked in current practice. CONCLUSIONS: We recommend the use of common RIs for general chemistry analytes in Hong Kong to prevent interpreter confusion, improve electronic data transfer, and unite laboratory practice. This is the first local study on this topic, and our data can lay the groundwork for increasing harmonisation of RIs across more laboratory tests.

Disseminated Sporotrichosis in a Bilby (Macrotis lagotis).

A male bilby (Macrotis lagotis) was presented to the Murdoch University Veterinary Anatomical Pathology Service following humane destruction due to severe lethargy. The bilby was emaciated with a focal ulcerated skin lesion on the dorsal tail base. Multifocal to coalescing foci of pyogranulomatous and often necrotizing inflammation was present within multiple organs, including the tail wound, adrenal glands, kidneys, lungs, brain, testes, lymph nodes, heart, liver, spleen and salivary glands. Admixed were abundant intrahistiocytic and extracellular pleomorphic yeast (round, oval and cigar-shaped) up to 6 µm diameter, often with a thin clear halo and occasional narrow-based budding. The diagnosis of disseminated sporotrichosis was confirmed via culture and sequencing of the internal transcribed spacer region of the causative agent, Sporothrix schenckii sensu lato. The route of entry of infection was considered most likely to have been via cutaneous inoculation of the tail base wound. To the authors' knowledge, this report describes the first known case of sporotrichosis in a native Australian animal.

Perceived challenges in pediatric palliative care among doctors and nurses in Hong Kong.

This study aims to examine perceived challenges, including knowledge, skills, self, and work environment, of professionals in providing pediatric palliative care (PPC) in Hong Kong and the differences in perceived challenges between groups. A total of 680 pediatric doctors and nurses participated in the survey. They tended to perceive the provision of PPC as difficult and considered "advanced skills" (those dealing with death-related issues) challenging. Findings indicate that nurses, professionals who are less experienced, do not have children, and have not received palliative care training perceived a higher level of challenges in providing PPC. Implications for training and support are discussed.

Evidence for regional aeolian transport of freshwater micrometazoans in arid regions.

While separated by large expanses of dry terrain unsuitable for aquatic biota, aridland waters possess high biodiversity. How aquatic micrometazoans disperse to, and colonize, these isolated ephemeral habitats are not well understood. We used a multi-faceted approach including wind tunnel and rehydration experiments, and next-generation sequencing to assess potential movement of diapausing propagules of aquatic invertebrates by anemochory across regional scales (102-105 km). Wind tunnel experiments using dry playa sediments with added micrometazoan propagules demonstrated that after entrainment by saltation and downwind transport were subsequently recoverable as viable animals when rehydrated. Further, rehydration of fallen natural dust yielded micrometazoans, including rotifers, gastrotrichs, microcrustaceans, and nematodes. Using conserved DNA primers, we identified >3,300 eukaryotic Operational Taxonomic Units (excluding fungi) in the dust including some taxa found in rehydration experiments. Thus, we provide strong evidence that anemochory can disperse micrometazoans among isolated, ephemeral ecosystems in North American deserts and likely elsewhere.

Peri-implant inflammation and marginal bone level changes around dental implants in relation to proximity with and bone level of adjacent teeth.

OBJECTIVES: This retrospective study assessed radiographic bone changes and prevalence of inflammation around teeth and neighbouring implants supporting a single-unit fixed dental prosthesis (FDP), in relation to implant- positioning and characteristics. MATERIAL AND METHODS: Patients with an implant-supported FDP in function for at least 1 year were recruited. The radiographic horizontal and vertical position of the implants were identified. Probing depth (PD), bleeding on probing (BOP) and radiographic bone level around implants and adjacent teeth at the time of placement, prosthesis delivery, and the most recent review were assessed. RESULTS: 98 patients with 195 implants were evaluated for a mean of 37.8 months. Survival rate was 99.6% and success ranged from 31.3% to 91.3% when different success criteria were utilized. Significantly greater interproximal bone loss around teeth and higher prevalence of interproximal peri-implant inflammation occurred when the horizontal distance of BL implants was <1 mm, but not with TL implants. There was no significant impact of the corono-apical positioning of the implants on marginal bone loss. CONCLUSION: Proximity of implants to adjacent teeth of <1 mm leads to increased prevalence of inflammation and interproximal bone resorption at the teeth adjacent to bone level implants.

Three-dimensional evaluation of mandibular asymmetry: a new classification and three-dimensional cephalometric analysis.

Mandibular asymmetry is common among orthognathic patients and exhibits great variation. The aim of this study was to propose a new classification of mandibular asymmetry by anatomical regions; namely R (ramus), B (mandibular body) and C (chin), in conjunction with a corresponding 'RBC' three-dimensional (3D) cephalometric analysis. The cone beam computed tomography data of 65 patients with mandibular asymmetry was retrieved to perform the RBC 3D cephalometric analysis and to investigate the characteristics of mandibular asymmetry. It was found that the more posteriorly in mandible, the more pronounced was the vertical asymmetry. Significant transverse asymmetry was only noted in mandibular body. Both mandibular body and chin were significantly asymmetric in length. Seven significant morphologic predictors of menton deviation were identified, namely lower dental midline shift, difference in ramus height, difference in chin length, difference in body length, body height on contralateral side, coronoid height on deviated side and body width on contralateral side, confirming the complex nature of mandibular asymmetry. This simple and concise classification allows comprehensive assessment of mandible morphology by anatomical regions which also facilitates diagnosis, treatment planning and communication in both clinical and research settings.

Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine.

BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 µg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.