As-Required Filgrastim for Late-Onset Neutropenia Complicating Long-Term Clozapine Treatment: a Case Report.

Clozapine is considered the most effective antipsychotic for schizophrenia, but it can cause neutropenia and even agranulocytosis. We describe the first case in Hong Kong involving the use of filgrastim, a recombinant form of human granulocyte colony-stimulating factor, to enable clozapine continuation therapy for a severely ill patient with treatment-resistant schizoaffective disorder who developed recurrent neutropenia after almost 20 years of continuous clozapine therapy. Therefore, clinical vigilance is important, regardless of clozapine treatment duration. Filgrastim can facilitate long-term clozapine therapy in patients with clozapine-induced neutropenia.

Drone versus ambulance for blood products transportation: an economic evaluation study.

BACKGROUND: Medical transportation is an essential step in health care services, and includes ground, air and water transportation. Among the important uses of medical transportation is the delivery of blood products in the event of a clinical emergency. Drone technology is the latest technological advancement that may revolutionize medical transportation globally. Nonetheless, its economic evaluation is scant and insufficient, whilst its cost-effectiveness remains controversial. The aim of this study was to compare the cost-effectiveness of drone transportation versus the ambulance. METHODS: The setting of the study was within a developing nation. An economic evaluation study of drone versus ambulance for emergency blood products transportation between the Sabah Women and Children Hospital (SWACH) and the Queen Elizabeth II Hospital (QEH2) on Borneo Island was conducted using the Cost-Effectiveness Analysis (CEA) technique. The total cost of each mode of transportation was calculated using the Activity Based Costing (ABC) method. Travel time was used as a denominator to estimate the Incremental Cost Effectiveness Ratio (ICER). RESULTS: For one clinical emergency in SWACH, a round trip of blood products transportation from SWACH to QEH2 costs RM1,266.02 (USD307.09) when using the ambulance, while the drone costs RM1,313.28 (USD319.36). The travel time for the drone was much shorter (18 min) compared to the ambulance (34 min). The Cost-Effectiveness Ratio (CER) of ambulance transportation was RM37.23 (USD9.05) per minute whilst the CER of drone transportation was RM72.96 (USD17.74) per minute. The ICER of drone versus ambulance was - 2.95, implying an increase of RM2.95 in cost for every minute saved using a drone instead of an ambulance. CONCLUSION: Although drone transportation of blood products costs more per minute compared to the ambulance, the significantly shorter transport time of the drone offset its cost. Thus, we believe there is good economic potential for drone usage for blood products transportation in developing nations particularly if the drone price decreases and its operational lifespan increases. Our limitation of a non-clinical denominator used in this study leads to the recommendation for use of clinical outcomes in future studies.

Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death.

Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.

Molecular epidemiological study of enterovirus D68 in hospitalised children in Hong Kong in 2014-2015 and their complete coding sequences.

Background: Human enterovirus D68 (EV-D68) was first isolated in 1962 and has aroused public concern recently because of a nationwide outbreak among children in 2014-2015 in the USA. The symptoms include fever, runny nose, sneezing, cough and muscle pains. It might be associated with severe respiratory illness in individuals with pre-existing respiratory conditions and its potential association with acute flaccid myelitis is under investigation. In Asia, EV-D68 cases have been reported in several countries. The study: We aimed to understand the EV-D68 prevalence and their genetic diversity in Hong Kong children. Methods: A total of 10 695 nasopharyngeal aspirate (NPA) samples from hospitalised patients aged <18 years were collected from September 2014 to December 2015 in two regional hospitals. NPAs tested positive for enterovirus/rhinovirus (EV/RV) were selected for genotyping. For those identified as EV-D68, their complete coding sequences (CDSs) were obtained by Sanger sequencing. A maximum-likelihood phylogeny was constructed using all EV-D68 complete coding sequences available in GenBank (n=482). Results: 2662/10 695 (24.9%) were tested positive with EV/RV and 882/2662 (33.1%) were selected randomly and subjected to molecular classification. EV-D68 was detected in 15 (1.70%) samples from patients with clinical presentations ranging from wheezing to pneumonia and belonged to subclade B3. Eight CDSs were successfully obtained. A total of 10 amino acid residue polymorphisms were detected in the viral capsid proteins, proteases, ATPase and RNA polymerase. Conclusion: B3 subclade was the only subclade found locally. Surveillance of EV-D68 raises public awareness and provides the information to determine the most relevant genotypes for vaccine development.

Palliative care: the need of the modern era.

There is a great need for palliative care in the modern era of medicine. Despite medical advances, patients with life-limiting illnesses still suffer significantly. Palliative care emerged a half century ago as an ethos based on compassion and care for patients and their families to relieve their suffering. It entails a paradigm shift from the biomedical model to the biopsychospiritual model. Palliative care is recognised by the World Health Organization as an essential part of the continuum of universal health coverage. In 2014, the World Health Assembly approved a resolution on "Strengthening of palliative care as a component of comprehensive care throughout the life course". Despite Hong Kong's relatively good local palliative care service coverage for patients who died of cancer and end-stage renal failure, service gaps for palliative care do exist among our ageing population with non-malignant life-limiting illnesses. We strongly urge the Hong Kong Government to develop our local palliative care policy in response to the World Health Assembly's resolution. Growing international and local evidence demonstrates the impacts of palliative care on patient outcomes, caregivers, and health care. Such outcomes can be service-based, disease-based, or symptom/suffering-based. The goal of palliative care is to relieve health-related suffering. Evidence-based management of pain, breathlessness, and psychospiritual suffering are discussed. Care in the end-of-life phase should be an integral part of palliative care, promoting patient choice, advance care planning, and good death.

Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Impact of advanced detector technology and iterative reconstruction on low-dose quantitative assessment of lung computed tomography density in a biological lung model.

PURPOSE: Quantitative computed tomography (QCT)-derived measures of lung density are valued methods for objectively characterizing lung parenchymal and peripheral airways disease and are being used in a growing number of lung disease focused trials. Detector and reconstruction improvements in CT technology have allowed for significant radiation dose reduction in image acquisition with comparable qualitative image quality. We report the impact of detector type and reconstruction type on QCT lung density measures in relation to decreasing dose indices. METHODS: Two sets of studies were completed in an in vivo pig model with a SOMATOM Definition Flash CT system: (a) prior to system upgrade with conventional detectors (UFC) and filtered back projection (FBP), and (b) post system upgrade with integrated electronic detectors (STELLAR) and iterative reconstruction (SAFIRE). CT data were acquired across estimated CT volume dose indices (CTDIvol ) ranging from 0.75 to 15 mGy at both inspiratory and expiratory breath holds. Semiautomated lung segmentations allowed calculation of histogram median, kurtosis, and 15th percentile. Percentage of voxels below -910 HU and -950 HU (inspiratory), and -856 HU (expiratory) were also examined. The changes in these QCT metrics from dose reduction (15 mGy down to 0.75 mGy) were calculated relative to paired reference values (15 mGy). Results were compared based on detector and reconstruction type. RESULTS: In this study, STELLAR detectors improved concordance with 15 mGy values down to 3 mGy for inspiratory scans and 6 mGy for expiratory scans. The addition of SAFIRE reconstruction in all acquired measurements resulted in minimal deviation from reference values at 0.75 mGy. CONCLUSION: The use of STELLAR integrated electronic detectors and SAFIRE iterative reconstruction may allow for comparable lung density measures with CT dose indices down to 0.75 mGy.

Spin-transfer torque generated in graphene based topological insulator heterostructures.

We studied the spin-transfer torque (STT) in graphene based normal-metal/topological-insulator/ferromagnet heterostructures (N/TI/F), which is induced by the helical spin-polarized current in the quantum spin Hall insulator. We found that the STT is comparable in magnitude to the STT in ferromagnetic-normal- ferromagnetic graphene junction, while not requiring additional ferromagnetic layer with fixed magnetization, which makes it advantageous for the manipulation of magnetic devices in spintronics. More interestingly, the STT is very robust in our proposed nanostructure, as it is immune to changes in the geometry due to an asymmetrically notch or the presence of random nanopores in the quantum spin Hall insulator. Our theoretical prediction suggests that graphene based quantum spin Hall insulator could be used for very efficient magnetization manipulation for magnetic materials.

Creation of quasi-Dirac points in the Floquet band structure of bilayer graphene.

We study the Floquet quasi-energy band structure of bilayer graphene when it is illuminated by two laser lights with frequencies [Formula: see text] and [Formula: see text] using Floquet theory. We focus on the dynamical gap formed by the conduction band with Floquet index = -1 and the valence band with Floquet index = +1 to understand how Dirac points can be formed. It is found that the dynamical gap does not have rotation symmetry in the momentum space, and quasi-Dirac points, where the conduction and valence bands almost touch, can be created when the dynamical gap closes along some directions with suitably chosen radiation parameters. We derive analytical expressions for the direction dependence of the dynamical gaps using Lowdin perturbation theory to gain a better understanding of the formation of quasi-Dirac points. When both radiations are circularly polarized, the gap can be exactly zero along some directions, when only the first and second order perturbations are considered. Higher order perturbations can open a very small gap in this case. When both radiations are linearly polarized, the gap can be exactly zero up to the fourth order perturbation and more than one quasi-Dirac point is formed. We also study the electron velocity around a dynamical gap and show that the magnitude of the velocity drops to values close to zero when the k vector is near to the gap minimum. The direction of the velocity also changes around the gap minimum, and when the gap is larger in value the change in the velocity direction is more gradual. The warping effect does not affect the formation of a Dirac point along the k x axis, while it prevents its formation when there is phase shift between the two radiations.

Spin-polarized transport in graphene nanoribbons with Rashba spin-orbit interaction: the effects of spatial symmetry.

We study the spin-dependent transport properties of graphene nanoribbons with Rashba spin-orbit interaction (SOI). It is found that highly spin polarized electrical currents can be produced in asymmetrically-notched graphene nanoribbons, and the polarization components are found to be along the x, y and z directions. The spin polarization is largely enhanced by breaking the spatial symmetries of ideal graphene nanoribbons with Rashba SOI, and the spin polarized electrical currents with higher flexibility in the orientation of the polarization can be generated. This offers new possibilities for the generation of high spin polarization in graphene nanoribbons without external magnetic fields.

The pattern of cervical smear abnormalities in marginalised women in Hong Kong.

INTRODUCTION: "Ripple Action" and "WE Stand" are projects co-organised by the Hong Kong Women Doctors Association. The two projects organise free cervical screening for low-income women, new immigrants from Mainland China, and ethnic minority women. The objective of this study was to analyse the pattern of cervical smear abnormalities in these marginalised women. METHODS: The study group consisted of 1189 marginalised women who participated in a free cervical screening campaign, including 324 low-income local Chinese, 540 new immigrants from Mainland China, and 325 ethnic minority women. The comparison group consisted of 1141 local Chinese who attended a well women clinic. The prevalence of cervical smear abnormalities was compared using Chi squared test. RESULTS: In the study group, 42.6% of women had never had a cervical smear. Compared with the comparison group, they had a significantly higher prevalence of cervical smear abnormalities (13.7% vs 1.4%; P<0.001), including atypical smear (10.8% vs 0.5%; P<0.001), low-grade lesion (1.8% vs 0.8%; P=0.036), and high-grade lesion (1.1% vs 0.1%; P=0.002). Logistic regression analysis showed that the strongest predictors for abnormal cervical smear were being South Asian (odds ratio=11.859; 95% confidence interval, 4.635-30.341), South-East Asian (6.484; 3.192-13.171), or new immigrant from Mainland China (6.253; 2.463-15.877). CONCLUSIONS: Marginalised women had a significantly higher prevalence of cervical smear abnormality than the general population and almost half had never had a cervical smear before. Outreach strategies are needed to enrol this population into screening programmes.

Electrically controllable sudden reversals in spin and valley polarization in silicene.

We study the spin and valley dependent transport in a silicene superlattice under the influence of a magnetic exchange field, a perpendicular electric field and a voltage potential. It is found that a gate-voltage-controllable fully spin and valley polarized current can be obtained in the proposed device, and the spin and valley polarizations are sensitive oscillatory functions of the voltage potential. In properly designed superlattice structure, the spin and valley polarizations can be reversed from -100% to 100% by a slight change in the external voltage potential. The energy dispersion relations of the superlattice structure are also investigated, which helps us to understand the effects of the superlattice structure. The switching of the spin direction and the valley of the tunneling electrons by a gate voltage enables new possibilities for spin or valley control in silicene-based spintronics and valleytronics.

A valley and spin filter based on gapped graphene.

We study highly valley- and spin-polarized current in single-layer gapped graphene without spin-orbit coupling. The structure considered is a three-barrier structure with one spin-splitting barrier and two electrical potential barriers with vector potentials. The electrons in the two valleys transmit differently because of the valley-dependent reflection between two adjacent barriers, while the spin-up and spin-down electrons transmit differently because of the spin splitting. The structure is different from other structures in which spin-orbit coupling plays an important role in the observation of valley- and spin-polarized current. We can control the spin and valley polarization by changing the width of the barrier or the strength of the spin splitting. The structure proposed in this paper can be used to make valley and spin devices.

Depression symptoms across cultures: an IRT analysis of standard depression symptoms using data from eight countries.

PURPOSE: Prevalence estimates of depression vary between countries, possibly due to differential functioning of items between settings. This study compared the performance of the widely used Hopkins symptom checklist 15-item depression scale (HSCL-15) across multiple settings using item response theory analyses. Data came from adult populations in the low and middle income countries (LMIC) of Colombia, Indonesia, Kurdistan Iraq, Rwanda, Iraq, Thailand (Burmese refugees), and Uganda (N = 4732). METHODS: Item parameters based on a graded response model were compared across LMIC settings. Differential item functioning (DIF) by setting was evaluated using multiple indicators multiple causes (MIMIC) models. RESULTS: Most items performed well across settings except items related to suicidal ideation and "loss of sexual interest or pleasure," which had low discrimination parameters (suicide: a = 0.31 in Thailand to a = 2.49 in Indonesia; sexual interest: a = 0.74 in Rwanda to a = 1.26 in one region of Kurdistan). Most items showed some degree of DIF, but DIF only impacted aggregate scale-level scores in Indonesia. CONCLUSIONS: Thirteen of the 15 HSCL depression items performed well across diverse settings, with most items showing a strong relationship to the underlying trait of depression. The results support the cross-cultural applicability of most of these depression symptoms across LMIC settings. DIF impacted aggregate depression scores in one setting illustrating a possible source of measurement invariance in prevalence estimates.

Has Choosing Wisely® affected rates of dual-energy X-ray absorptiometry use?

UNLABELLED: Reducing overuse of tests such as dual-energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue. We evaluated trends in DXA ordering before and after Choosing Wisely recommendations were released. We found no significant difference in ordering trends suggesting that other initiatives are needed to change behavior. INTRODUCTION: Reducing overuse of tests such as dual-energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue, but trends in care are difficult to change. We evaluated (1) trends in DXA ordering before and after the Choosing Wisely recommendation release and (2) patterns of key characteristics that indicate a potentially appropriate DXA scan order. METHODS: We performed a retrospective longitudinal analysis of electronic health record data at a multi-specialty, ambulatory care network of 34 practices across Maryland and Washington, DC. Since the Choosing Wisely DXA recommendation was released April 2012, the study periods were April-December 2011 (pre-initiative) and April-December 2012 (post-initiative). Women between 50 and 64 years with primary care encounters, and primary care providers who saw ten or more women in the study population in both pre and post periods were included. RESULTS: For 42,320 eligible patients, the mean provider ordering rate was 2.6 % pre-initiative and 2.0 % post-initiative; there was no significant difference in trend over time. Over 70 % of the population had no characteristics associated with potentially appropriate DXA ordering. Low body mass index, current smoker status, and osteopenia were the most common characteristics indicating potentially appropriate DXA orders. Patients with any of these three characteristics had DXA ordering rates between 3-20 %. CONCLUSIONS: The trend in provider ordering rates of DXA scans did not decrease after the release of the DXA Choosing Wisely recommendation. Targeted initiatives addressing providers with high ordering rates will be needed to change behavior.

Nearly perfect valley filter in silicene.

We demonstrate theoretically how a perfect valley filter can be obtained in silicene under the effects of a ferromagnetic stripe and an electric field perpendicular to silicene. A ferromagnetic stripe or an electric field alone can not generate any valley polarization in silicene, but a combination of them can make a perfect valley filter. Two configurations, one with magnetization of the ferromagnetic stripe being perpendicular to the silicene plane and one being parallel to the current direction, are considered. Our proposed device is useful for the realization of a valley beam filter in the development of valleytronic devices.

Association of endothelin-1 and matrix metallopeptidase-9 with metabolic syndrome in middle-aged and older adults.

BACKGROUND: Metabolic syndrome (MetS) contains a cluster of cardiovascular risk factors. People with MetS are more susceptible to cardiovascular disease, diabetes mellitus, and cancer. Endothelin-1 (ET-1) and matrix metallopeptidase-9 (MMP-9) have been implicated in the development of cardiovascular diseases, diabetes mellitus and cancers. This cross-sectional study aimed to examine the association of ET-1 and MMP-9 with MetS in middle-aged and older Hong Kong Chinese adults. METHODS: 149 adults aged 50 to 92 (n = 75 for non-MetS group and n = 74 for MetS group) were examined. All subjects were screened for MetS according to the diagnostic guideline of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Serum levels of ET-1 and MMP-9 were measured. Independent t test was used to detect differences between non-MetS and MetS groups and between subjects with or without certain metabolic abnormality. The association of the serum concentration of MMP-9 and ET-1 with MetS parameters were examined by Pearson's correlation analysis. RESULTS: Serum level of ET-1 is higher in MetS-positive subjects and in subjects with high blood pressure, elevated fasting blood glucose, and central obesity. The serum concentration of MMP-9 is higher in subjects positively diagnosed with MetS and subjects with high blood pressure, elevated fasting blood glucose, low blood high-density lipoprotein-cholesterol (HDL-C), high blood triglycerides, and central obesity. Correlation analyses revealed that serum concentration of ET-1 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. MMP-9 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. CONCLUSION: Serum ET-1 is higher in subjects with hypertension, hyperglycemia, central obesity or MetS. Serum MMP-9 is higher in subjects diagnosed with MetS or having either one of the MetS parameters. Both circulating levels of ET-1 and MMP-9 are correlated to systolic blood pressure, waist circumference, fasting blood glucose, HDL-C, and age. Further research is needed to fully dissect the role of ET-1 and MMP-9 in the development of cancers, diabetes and cardiovascular disease in relation to MetS.

Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

INTRODUCTION: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system. METHODS: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel. RESULTS: Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified. CONCLUSIONS: Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients.

Effects of van der Waals interaction and electric field on the electronic structure of bilayer MoS2.

The modification of the electronic structure of bilayer MoS2 by an external electric field can have potential applications in optoelectronics and valleytronics. Nevertheless, the underlying physical mechanism is not clearly understood, especially the effects of the van der Waals interaction. In this study, the spin orbit-coupled electronic structure of bilayer MoS2 has been investigated using the first-principle density functional theory. We find that the van der Waals interaction as well as the interlayer distance has significant effects on the band structure. When the interlayer distance of bilayer MoS2 increases from 0.614 nm to 0.71 nm, the indirect gap between the Γ and Λ points increases from 1.25 eV to 1.70 eV. Meanwhile, the energy gap of bilayer MoS2 transforms from an indirect one to a direct one. An external electric field can shift down (up) the energy bands of the bottom (top) MoS2 layer and also breaks the inversion symmetry of bilayer MoS2. As a result, the electric field can affect the band gaps, the spin-orbit interaction and splits the valance bands into two groups. The present study can help us understand more about the electronic structures of MoS2 materials for potential applications in electronics and optoelectronics.