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This short essay is an attempt to record some of the early history of the US Peace Corps in the former British Crown Colony of North Borneo, now Sabah, Malaysia. [...]

Eric LK Chan,1 Chengfei Zhang,2 Gary SP Cheung2 1Department of Health, Government of Hong Kong SAR, Hong Kong, Special Administrative Region; 2Comprehensive Dental Care (Endodontics), Faculty of Dentistry, University of Hong Kong, Hong Kong Special Administrative Region of the People's Republic of China Purpose: The aim of this study was to evaluate the cytotoxic effect of a novel nano-silver particle (25.2±6.5 nm) endodontic irrigant (0.2 mM) and compare it with 3% sodium hypochlorite. Materials and methods: Two cell types, mouse fibroblast National Institutes of Health 3T3 (NIH 3T3) and primary human periodontal ligament stem cell (hPDLSCs) were used in a test for the effect of direct and indirect (by separating the agent and cell with a layer of agar) exposure to the two solutions. In the direct exposure experiment, ten groups of cell cultures were exposed to one dilution (3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 or 1:7) of a nano-silver irrigant for 48 hours; the concentration-response function was estimated by determining the number of viable cells in each group by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The 50% lethal dose of the testing irrigant for NIH3T3 and hPDLSCs were estimated. In the second part of the experiment, a modified agar overlaying technique was applied. Twelve culture wells (6-well plate) were divided into three groups (n=4). The cell lysis zone (cytotoxic range) created by the stock nano-silver solution, 3% sodium hypochlorite, and an isotonic phosphate buffering saline (control) was measured by two double blinded observers (Kappa score =100%). The cytotoxic score of specific irrigant was derived by modified Sjögren's method. Results: The 50% lethal doses of the testing nano silver irrigant for NIH 3T3 and hPDLSCs after 48 hours of direct exposure were 0.58 and 0.608 dilution of stock solution, respectively.The cytotoxic scores of nano-silver irrigant and control (phosphate buffered saline) on NIH 3T3 were 0.25 (95% confidence interval [CI] =0 to 1.04) and 0 (95% CI =0 to 0); and on hPDLSCs were 0.13 (95% CI =0 to 0.52) and 0.25 (95% CI =0 to 1.04), respectively. Toxicity of the test and control group on both mouse fibroblasts (P>0.05) and hPDLSCs (P=1.00) was not statistically different. Conclusion: Our results showed that the nano-silver irrigant was non-cytotoxic to both NIH 3T3 and hPDLSCs. Keywords: root canal irrigant, biocompatibility, hPDLSC, agar overlay, MTT

Abstract Background In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. Methods Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). Results Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10–12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive β5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2–4 fold increase in the mRNA and protein levels of the constitutive β5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. Conclusions These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease.

Background: Physical rehabilitation of critically ill patients may improve physical outcomes; however, the relative benefits and risks with patients requiring vasoactive drugs is currently unknown. A feasibility study is needed to inform the design of a future trial required to address this issue., Methods: A two-phase exploratory observational feasibility study was carried out: A retrospective study to clarify the current practice of rehabilitation with patients receiving vasoactive drugs to inform future trial interventions and design.A prospective study exploring recruitment and outcome measurement. Intensive care patients receiving vasoactive drugs were recruited and asked about the acceptability of a future trial. The feasibility of using an adverse event tool was measured during rehabilitation. Patients were followed up after 60 days to describe the feasibility of measuring outcomes for a future trial., Results: Retrospective study (n = 78): Twenty-one percent of patients took part in physical rehabilitation whilst receiving vasoactive drugs. Of 321 days with vasoactive drugs administered, physical rehabilitation occurred on 27 days (8%). Prospective study (n = 40): Eighty-one percent of participants indicated acceptability of being recruited into a future trial (n = 37). Eighty-eight percent of clinicians found it acceptable to randomise patients into either early rehabilitation or standard care. The adverse event tool was implemented by researchers with 2% loss of information. Finally, a 100% follow-up rate at day 60 was achieved for mortality outcomes. Follow-up rates were 70% for the EQ-5D (5 level), 65% for the World Health Organisation's Disability Assessment Schedule 2.0 and RAND 36-item Health Survey 1.0 and 26% for the 6-minute walk test., Conclusions: This study found a low frequency of physical rehabilitation occurring with intensive care patients receiving vasoactive drugs. A high proportion of clinicians and patients found a future RCT within this patient group acceptable. Mortality and patient-reported outcomes were the most feasible to measure., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HRW reports personal lecture fees from Brunel University and the University of East London., (Copyright: © 2025 Woodbridge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Head-and-neck cancer (HNC) can present with life.threatening symptoms in the emergency department. Patients can sometimes be misdiagnosed with pulmonary disease due to similar signs and symptoms, ultimately leading to delayed diagnosis and potentially devastating consequences. Reasons for this include lack of awareness of patient risk factors and knowledge of the myriad of presenting complaints in the disease process among physicians working in primary care and in the emergency department. This article explores the contemporary risk factors and common presenting symptoms and discusses initial management for a patient with potential head-and-neck malignancy. Emergency presentations of HNC are wide ranging and can overlap with common respiratory pathologies. Clinician awareness of this can assist the team in deciding what appropriate examination and investigations are required to reduce the risk of delaying diagnosis and further treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Emergencies, Trauma, and Shock.)

Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma., Methods: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 10 6 plaque-forming unit (PFU) followed by ≤ 4 × 10 8 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis., Results: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm., Conclusion: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

Blunt chest trauma is a rare cause of acute coronary syndrome and can be masked by other injuries in polytrauma patients. It can have devastating consequences due to damage to the myocardial tissue if left un-recognized. Myocardial injury can result in life-threatening arrhythmias and complications such as systolic and diastolic dysfunction. This can significantly affect patients' quality of life. A 34-year-old man involved in a paragliding incident in Kazakhstan. His equipment failed at 30 meters height and result him to be propelled at high velocity to the ground. He sustained multiple injuries including spinal fractures, lung contusions and a mediastinal haematoma. He was transported to a local hospital and noted to have ST segment elevation on his admission electrocardiogram (ECG). He underwent an angiogram that showed sub-occlusion of his left anterior descending (LAD) artery. This resulted in a time-critical Percutaneous Coronary Intervention (PCI). He was stabilized and repatriated to the UK to manage of remaining injuries., Competing Interests: None declared.

The winter 2018/19 influenza season in Hong Kong has been predominated by influenza A(H1N1)pdm09 as at January 2019. We enrolled 2,016 children in three public hospitals in Hong Kong between 2 September 2018 and 11 January 2019. Using the test-negative approach, we estimated high early season effectiveness of inactivated influenza vaccine against influenza A or B of 90% (95% confidence interval (CI): 80-95%) and 92% (95% CI: 82-96%) against influenza A(H1N1)pdm09.

Tyrosine kinase inhibitors are effective treatments for cancers. Knowing the specific kinase mutants that drive the underlying cancers predict therapeutic response to these inhibitors. Thus, the current protocol for personalized cancer therapy involves genotyping tumors in search of various driver mutations and subsequently individualizing the tyrosine kinase inhibitor to the patients whose tumors express the corresponding driver mutant. While this approach works when known driver mutations are found, its limitation is the dependence on driver mutations as predictors for response. To complement the genotype approach, we hypothesize that a phosphoarray platform is equally capable of personalizing kinase inhibitor therapy. We selected head and neck squamous cell carcinoma as the cancer model to test our hypothesis. Using the receptor tyrosine kinase phosphoarray, we identified the phosphorylation profiles of 49 different tyrosine kinase receptors in five different head and neck cancer cell lines. Based on these results, we tested the cell line response to the corresponding kinase inhibitor therapy. We found that this phosphoarray accurately informed the kinase inhibitor response profile of the cell lines. Next, we determined the phosphorylation profiles of 39 head and neck cancer patient derived xenografts. We found that absent phosphorylated EGFR signal predicted primary resistance to cetuximab treatment in the xenografts without phosphorylated ErbB2. Meanwhile, absent ErbB2 signaling in the xenografts with phosphorylated EGFR is associated with a higher likelihood of response to cetuximab. In summary, the phosphoarray technology has the potential to become a new diagnostic platform for personalized cancer therapy., (© 2017 UICC.)

In this work, Direct Numerical Simulations (DNS) of a pendular liquid bridge formed between two relatively moving particles are performed to evaluate the normal component of the viscous force exerted on the particles. The viscous force obtained are non-dimensionalised in order to clarify the parameters which can affect the dimensionless force. The DNS results are compared with the viscous force models in literature which are commonly used in DEM simulations. It is found that these models cannot be used with large inter-particle separation distance. A new and more accurate viscous force model is proposed from the DNS results which can be directly implemented in the DEM framework., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong., Participants: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society., Evidence: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution., Consensus Process: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature., Conclusions: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

From 1 September 2015 through 31 January 2016, we enrolled 2068 children 6 months to 17 years of age admitted to hospital with a febrile acute respiratory infection in our test-negative study. Information on receipt of 2015-16 northern hemisphere inactivated influenza vaccination was elicited from parents or legal guardians. Using conditional logistic regression adjusting for age and matching on calendar time, we estimated influenza vaccine effectiveness against hospitalization with influenza A or B to be 79.2% (95% confidence interval: 42.0%-92.4%). Annual influenza vaccination should be more widely used in children in Hong Kong., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: To examine the effect of acceleration and deceleration distance (0, 1, 2 and 3 m) on the comfortable and maximum walking speeds in: (i) the 5-m walk test (5mWT); and (ii) the 10-m walk test (10mWT) in people with chronic stroke., Design: Cross-sectional study., Setting: University-based rehabilitation centre., Subjects: Thirty individuals with chronic stroke., Methods: Timed walking at comfortable and maximum walking speeds in the 5mWT and 10mWT with different acceleration and deceleration distances (0, 1, 2 and 3 m)., Results: The comfortable walking speed in the 5mWT with 0 m acceleration and deceleration distance was significantly slower than that with 1, 2 or 3 m acceleration and deceleration distances (p < 0.0083), but there was no significant difference among 1, 2 and 3 m acceleration and deceleration distances. No significant difference was found in the maximum walking speed in the 5mWT, or in the comfortable and maximum walking speeds of the 10mWT., Conclusion: Adoption of 1 m acceleration and deceleration distance is recommended when measuring the comfortable walking speed in the 5mWT in people with stroke. Neither acceleration nor deceleration distance is needed when measuring the maximum walking speed in the 5mWT, the comfortable walking speed or the maximum walking speed in the 10mWT.

Unlabelled: EGFR is a popular therapeutic target for many cancers. EGFR inhibitors have been tested in children with refractory neuroblastoma. Interestingly, partial response or stable disease was observed in a few neuroblastoma patients. As EGFR mutations are biomarkers for response to anti-EGFR drugs, primary neuroblastoma tumors and cell lines were screened for mutations. A novel EGFR extracellular domain deletion mutant, EGFRΔ768, was discovered and the biologic and biochemical properties of this mutant were characterized and compared with wild-type and EGFRvIII receptors. EGFRΔ768 was found to be constitutively active and localized to the cell surface. Its expression conferred resistance to etoposide and drove proliferation as well as invasion of cancer cells. While EGFRΔ768 had similarity to EGFRvIII, its biologic and biochemical properties were distinctly different from both the EGFRvIII and wild-type receptors. Even though erlotinib inhibited EGFRΔ768, its effect on the mutant was not as strong as that on wild-type EGFR and EGFRvIII. In addition, downstream signaling of EGFRΔ768 was different from that of the wild-type receptor. In conclusion, this is the first study to demonstrate that neuroblastoma express not only EGFRvIII, but also a novel EGFR extracellular domain deletion mutant, EGFRΔ768. The EGFRΔ768 also possesses distinct biologic and biochemical properties which might have therapeutic implications for neuroblastoma as well as other tumors expressing this novel mutant., Implications: Neuroblastoma expressed a novel EGFR mutant which possesses distinct biologic and biochemical properties that might have therapeutic implications. Mol Cancer Res; 14(8); 740-52. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: We estimated vaccine effectiveness (VE) against pediatric influenza B hospitalizations in Hong Kong year round between November 2001 and October 2014., Methods: We conducted a test-negative year-round study, enrolling children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Children were tested for influenza A and B. Conditional logistic regression was used to estimate overall and lineage-specific vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive for influenza B versus negative for influenza A and B, adjusting for age and sex and matching by calendar week of recruitment., Results: Of the 6013 children included in the analysis, 262 tested positive for influenza B. Vaccination coverage was low: 6.5% in the influenza B positive children when compared with 8.8% in children who tested negative for both influenza A and B (p=0.248). Overall, VE was 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization despite variable co-circulation of both lineages in all years. VE for Victoria-like virus calculated from 3 years when the vaccine was lineage-matched was 59.1% (95% CI: 6.2, 82.2%). Lineage-matched VE for Yamagata-like virus was -8.8% (95% CI: -215.4, 62.5%) in a clade mismatch season. With wide confidence intervals, we were unable to demonstrate cross-lineage protection: VE against the mismatched B/Yamagata-like virus was 9.5% (95% CI: -240.4, 76.0%) in 2011/12 and against mismatched B/Victoria-like virus in 2013/14 was 42.7% (95% CI: -368.6, 93.0%)., Conclusions: TIV conferred an overall VE of 47.6% (95% CI: 10.0, 69.4%) against influenza B hospitalization in children despite variable co-circulation of both lineages in all years. Lineage-matched VE for Yamagata-like virus was poor and may be related to clade mismatch. Cross-lineage protection was not observed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: We sought to document the incidence of pediatric hospitalization for bacterial pneumonia before universal childhood conjugate pneumococcal vaccination using two different methods of diagnosis., Methods: By following the World Health Organization (WHO) chest radiography (CXR) protocol, two radiologists independently read the CXRs of a cohort of systematically recruited children younger than 5 years. The children had acute respiratory infections and were admitted to one of two hospitals that care for 72.5% of all pediatric admissions on Hong Kong Island. Medical records were reviewed for clinical manifestation and to identify bacterial pneumonia diagnosed by pediatricians., Results: In children younger than 5 years, the incidences of bacterial pneumonia, as diagnosed by pediatricians and by the WHO CXR standard, were 775.7 per 100,000 population [95% confidence interval (CI, 591.8-998.3)] and 439.5 per 100,000 population (95% CI, 304.6-614.5), respectively. The study period was from 2002 to 2004., Conclusion: This study provided a reliable baseline estimate of the hospitalization burden of pneumococcal pneumonia in Hong Kong children before the advent of universal conjugate pneumococcal vaccination., (Copyright © 2014. Published by Elsevier B.V.)

We investigated differences in outcomes between 68 children hospitalized with macrolide-sensitive Mycoplasma pneumoniae pneumonia (MSMP group) and 25 children hospitalized with macrolide-resistant M. pneumoniae pneumonia (MRMP group). In the MRMP group, 19 children received macrolides and clinical failure occurred in six of which five had pneumonia progression during therapy., (Copyright © 2014. Published by Elsevier B.V.)

The proto-oncogenic ALK is a druggable receptor tyrosine kinase for cancer treatment. Two small molecule inhibitors of ALK, crizotinib and ceritinib, have been recently approved for the treatment of metastatic non-small-cell lung cancer, with marked improvement of progression-free survival of patients. Independent case reports also indicate their potential therapeutic activity in other ALK-rearranged cancers. Numerous single-agent and combination therapy trials are ongoing in lung and many other cancers. Results of these trials are greatly anticipated. Here, we summarize our current understanding of ALK signaling, genomic aberrations in cancer and emerging mechanisms of drug resistance. We will also provide a timely review on all ALK inhibitors and their current status of development in clinical settings.

Background: The level of patient safety and outcomes accomplished depends on the quality of care provided. Previous studies found that nurse-to-patient ratio, practice environment, and nursing education were significant predictors of patient outcomes. However, the outcomes measured in previous studies were mainly inpatient mortality and failure-to-rescue rates. Few nurse-sensitive patient outcomes have been measured that quantify nurses' contribution to patient care. Selecting appropriate outcomes that reflect the clinically relevant effect of nursing care is important. Moreover previous studies were largely cross-sectional and retrospective. These research designs are limited in their ability to explain the casual links between the variables examined. This study is aimed at determining the associations among staffing levels, skill mix of baccalaureate-prepared registered nurses, and practice environment on nurse-sensitive outcomes for medical and surgical patients in public hospitals in Hong Kong., Method/designs: A multi-method research design will be adopted. The sample includes all medical and surgical wards of four major public hospitals that offer 24-h accident and emergency services. Multiple responses from registered nurses who work in the study wards will be collected over 12 months to examine their individual characteristics and perceptions of the practice environment. A 12-month prospective observational study will be performed to determine the association between nurse staffing levels, the practice environment, and nurse-sensitive patient outcomes including pressure ulcers, falls and restraint prevalence, urinary catheter-associated urinary tract infections, and central line catheter-associated bloodstream infections. Multilevel Cox proportional hazards models will be employed to examine the association between these patient outcomes and the explanatory nursing factors of primary interest (nurse staffing levels, education composition, and practice environment), with adjustment for all patient-, ward- and hospital-level potential confounders (age, sex, diagnosis, comorbidities, level of surgical invasiveness, mortality, length of stay, and type of admission)., Discussion: It is anticipated that knowledge of the association between nurse staffing levels, the practice environment, and nurse-sensitive outcomes will inform the provision of quality and timely patient care. This study will provide a landmark report that is of relevance and importance to patients and to hospital stakeholders and managers, health policy makers, nurses, and educators who advocate patient benefits., Trial Registration: Clinical Trials Registry CCTCTR CUHK&#95;CCT00460 . Date of trial registration: 02 July 2015.

This study assessed pneumococcal carriage in the early periods after routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in Hong Kong. Nasopharyngeal swabs were obtained from 1110 children (<5 years) admitted with acute illness during September 2010-August 2013. Pneumococcal carriage rate was 13.5% in unvaccinated children, 14.1% in children who had ≥1 PCV dose and 15.3% in children who had ≥3 PCV doses. Nonv-PCV13 serotypes comprised 56.4% of all isolates. The most common serogroup/types were 15 (15A, 5.1%; 15B, 10.3%; 15C, 9.6%; 15F, 0.6%), 19F (17.9%), 6A (7.1%) and 6C (7.1%). Carriage of serogroup 15 was more common among vaccinated children (4.1% versus 0.6%, P = 0.033). Molecular typing revealed that expansion of several clones (clonal complex, CC63, CC199, CC1262, CC3397) was responsible for the increase in serogroup 15. Almost all CC63 and CC3397 isolates were nonsusceptible to both penicillin and erythromycin. The finding highlights the emergence of serogroup 15 following PCV13 use., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Study Objectives: The objective of this study was to determine whether tongue fat is increased in obese sleep apneics compared to obese subjects without sleep apnea. We hypothesized that excess fat is deposited in the tongue in obese patients with sleep apnea., Design: Case-control design., Setting: Academic medical center., Patients: We examined tongue fat in 31 obese controls (apnea-hypopnea index, 4.1 ± 2.7 events/h) and 90 obese apneics (apnea-hypopnea index, 43.2 ± 27.3 events/h). Analyses were repeated in a subsample of 18 gender-, race-, age-, and BMI-matched case-control pairs., Interventions: All subjects underwent a MRI with three-point Dixon magnetic resonance imaging. We used sophisticated volumetric reconstruction algorithms to study the size and distribution of upper airway fat deposits in the tongue and masseter muscles within apneics and obese controls., Measurements and Results: The data supported our a priori hypotheses that after adjustment for age, BMI, gender, and race, the tongue in apneics was significantly larger (P = 0.001) and had an increased amount of fat (P = 0.002) compared to controls. Similar results were seen in our matched sample. Our data also demonstrate that within the apneic and normal tongue, there are regional differences in fat distribution, with larger fat deposits at the base of the tongue., Conclusions: There is increased tongue volume and deposition of fat at the base of tongue in apneics compared to controls. Increased tongue fat may begin to explain the relationship between obesity and obstructive sleep apnea., (© 2014 Associated Professional Sleep Societies, LLC.)

This study aims to explore the roles and responsibilities of seven newly appointed nurse consultants (NCs) in various clinical specialties in Hong Kong as a pioneer project. Qualitative approaches using direct observation and semi-structured interviews were adopted with two full-day observations on the seven NCs plus 56 semi-structured interviews of NCs, nurses, doctors and patients. Five major NCs' roles and responsibilities had been identified, namely providing expert practice, initiating service development, leading education, guiding continuous quality improvement (CQI) and conducting research and providing evidence-based practice. The seven NCs within this study have by and large achieved building professional excellence, respect and trust within their own spheres. It is strongly recommended that the NC post be formally established in the new Nurses Career Structure to enable expert clinical nurses to develop a clinical career to contribute to service and patient care to its maximum., (© 2013 Wiley Publishing Asia Pty Ltd.)

Background: Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions., Methods: We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment., Results: Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: -25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B., Conclusions: Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Rationale: The metabolic activity of the tongue is unknown in patients with obstructive sleep apnea (OSA). Tongue electromyographic (EMG) activity is increased in patients with OSA. This increase in tongue EMG activity is thought to be related to either increased neuromuscular compensation or denervation with subsequent reinnervation of the muscle fibers. Increased glucose uptake in the tongue would support increased neuromuscular compensation, whereas decreased glucose uptake in the tongue would support denervation with subsequent reinnervation of the muscle fibers., Objectives: To investigate the metabolic activity of the genioglossus and control upper airway muscles in obese patients with sleep apnea compared with obese control subjects., Methods: Obese subjects with and without OSA underwent a standard overnight sleep study to determine an apnea-hypopnea index. Each subject had a positron emission tomography with [(18)F]-2-fluoro-2-deoxy-D-glucose scan in addition to noncontrast computed tomography or magnetic resonance imaging. Glucose uptake was quantified within upper airway tissues with the standardized uptake value., Measurements and Main Results: We recruited 30 obese control subjects (apnea-hypopnea index, 4.7 ± 3.1 events per hour) and 72 obese patients with sleep apnea (apnea-hypopnea index, 43.5 ± 28.0 events per hour). Independent of age, body mass index, sex, and race, patients with OSA had significantly reduced glucose uptake in the genioglossus (P = 0.03) in comparison with obese normal subjects. No differences in standardized uptake value were found in the control muscles (masseter [P = 0.38] and pterygoid [P = 0.70]) and subcutaneous fat deposits (neck [P = 0.44] and submental [P = 0.95]) between patients with OSA and control subjects., Conclusions: There was significantly reduced glucose uptake in the genioglossus of patients with sleep apnea in comparison with obese normal subjects with [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography imaging. The reduction in glucose uptake was likely secondary to alterations in tongue muscle fiber-type or secondary to chronic denervation. The reduced glucose uptake argues against the neuromuscular compensation hypothesis explaining the increase in tongue EMG activity in obese patients with OSA.

Objectives: We aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in Hong Kong., Methods: The pediatric age-specific rates of influenza A hospitalization in Hong Kong for 2004-2011 which encompassed the emergence of H1N1pdm09 were extrapolated from admissions to 2 hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza A was detected by immunofluorescence, culture and/or PCR on nasopharyngeal aspirates., Results: Influenza A caused high rates of hospitalization in children with year to year fluctuations. The highest hospitalization burden was seen with H1N1pdm09 in 2009. Additional factors affecting hospitalization were the proportion of viral circulation among different subtypes, and antigenic drifts. Taking these into effect, an H3N2 dominated year was not always associated with more hospitalizations than a 'seasonal' H1N1 year. Hospitalization burden was higher in seasons when drifted viruses of H1N1 or H3N2 dominated. No hospitalization was documented in infants <6 months of age during years when an undrifted virus circulated (2006 for H1N1 and 2008 for H3N2) but significant hospitalization was observed with a drifted or shifted virus (2004, 2005, 2007 and 2010 for H3N2, and 2009 for H1N1pdm09)., Conclusions: We documented a consistently high pediatric hospitalization burden of influenza A. Knowledge of antigenic changes and their proportion of circulation aids in the interpretation of impact of the subtypes. Year-to-year variation in hospitalization rates in young infants appeared to correlate with antigenic variation, lending support to the role of protection from maternal antibodies.

Background: Poisson model has been widely applied to estimate the disease burden of influenza, but there has been little success in providing reliable estimates for other respiratory viruses., Methods: We compared the estimates of excess hospitalization rates derived from the Poisson models with different combinations of inference methods and virus proxies respectively, with the aim to determine the optimal modeling approach. These models were validated by comparing the estimates of excess hospitalization attributable to respiratory viruses with the observed rates of laboratory confirmed paediatric hospitalization for acute respiratory infections obtained from a population based study., Results: The Bayesian inference method generally outperformed the classical likelihood estimation, particularly for RSV and parainfluenza, in terms of providing estimates closer to the observed hospitalization rates. Compared to the other proxy variables, age-specific positive counts provided better estimates for influenza, RSV and parainfluenza, regardless of inference methods. The Bayesian inference combined with age-specific positive counts also provided valid and reliable estimates for excess hospitalization associated with multiple respiratory viruses in both the 2009 H1N1 pandemic and interpandemic period., Conclusions: Poisson models using the Bayesian inference method and virus proxies of age-specific positive counts should be considered in disease burden studies on multiple respiratory viruses.

Along with the most common mutation, JAK2V617F, several other acquired JAK2 mutations have now been shown to contribute to the pathogenesis of myeloproliferative neoplasms (MPNs). However, here we describe for the first time a germline mutation that leads to familial thrombocytosis that involves a residue other than Val617. The novel mutation JAK2R564Q, identified in a family with autosomal dominant essential thrombocythemia, increased cell growth resulting from suppression of apoptosis in Ba/F3-MPL cells. Although JAK2R564Q and JAK2V617F have similar levels of increased kinase activity, the growth-promoting effects of JAK2R564Q are much milder than those of JAK2V617F because of at least 2 counterregulatory mechanisms. Whereas JAK2V617F can escape regulation by the suppressor of cytokine signaling 3 and p27/Kip1, JAK2R564Q-expressing cells cannot. Moreover, JAK2R564Q-expressing cells are much more sensitive to the JAK inhibitor, ruxolitinib, than JAK2V617F-expressers, suggesting that lower doses of this drug may be effective in treating patients with MPNs associated with alternative JAK2 mutations, allowing many undesirable adverse effects to be avoided. This work provides a greater understanding of the cellular effects of a non-JAK2V617F, MPN-associated JAK2 mutation; provides insights into new treatment strategies for such patients; and describes the first case of familial thrombosis caused by a JAK2 residue other than Val617.

Background: The position of nurse consultant (NC) was introduced in Hong Kong by the Hospital Authority in January 2009. Seven NCs were appointed in five clinical specialties: diabetes, renal, wound and stoma care, psychiatrics, and continence. This was a pilot to explore the impact of the introduction of NCs on patient health and service outcomes., Methods: The present paper describes a historically matched controlled study. A total of 280 patients, 140 in each cohort under NC or non-NC care, participated in the study. The patient health and service outcomes of both cohorts were evaluated and compared: accident and emergency visits, hospital admissions, length of hospital stays, number of acute complications, number of times of treatment or regimen altered by nurses according to patient's condition, glycated haemoglobin A1c (HbA1c) levels, urea and urea-to-creatinine ratios, and number of wound dressings for patients in corresponding specialty units. A patient satisfaction instrument was also used to assess the NC cohort., Results: The study showed that patients under NC care had favourable patient health and service outcomes compared with those under non-NC care. The NC cohort also reported a high level of patient satisfaction., Conclusions: The study demonstrates that the introduction of NCs in specialty units may have a positive impact on patients' health and service outcomes. The high level of patient satisfaction scores indicates that patients appreciate the care they are receiving with the introduction of NCs.

Objective: To evaluate the use of selective agar and broth combination in a regular laboratory daily workflow., Design: Swabs from 173 surveillance specimens were inoculated onto half of the Bio-Rad MRSASelect (M), SaSelect (S) and Sheep Blood agars (SBA) and the swab placed in the LIM broth. After overnight incubation, 10 microL of the LIM broth was inoculated onto the other half of the three agars and incubated overnight. All the and examined worked after agars were up approximate 14-18 hours of incubation for day one and two according to the regular workflow of the laboratory, without incubating for the full 24 hours for each incubation day. M agar and SBA were evaluated for Methicillin-Resistant Staphylococcus aureus (MRSA), while the S agar was evaluated for Staphylococcus aureus (SA) based on typical colony morphology development. Colonies on the SBA were picked and processed for definitive identification and cefoxitin susceptibility result., Setting: Trinity Medical Center, a community hospital with network hospitals, Patients: Patient admitted to the hospital submitted swab for surveillance culture, Results: There were a total of 29 MRSA isolated in the study. On day one, both M agar and SBA detected 14 MRSA (48.3%) and on day two, M agar detected 10 (82.7%), while SBA detected 8 (75.8%) additional MRSA. LIM broth added 5 more MRSA to both agars on day 2, to give M agar a total of 29 (100%) and SBA agar a total of 27 (93.1%) of MRSA from the 173 specimens. There were a total of 62 SA isolated. Both the S agar and SBA isolated 34 (54.8%) on day one and 15 more (79%) on day two. The LIM broth added an additional 13 SA for both agars on day two., Conclusion: Using half of the agar plate for the initial swab and the other half for the broth creates an economic strategy for the detection of MRSA using the M agar and SA using the S agar. Both the M and S agars provided excellent identification and recovery of MRSA or SA based on color and colony morphology unless the colony was too young for color development. The color morphology from the M and S agars was distinguishable overnight after being subcultured from LIM broth. Working up the specimen according to the workflow of the laboratory without having to wait for each plate to incubate a full 24 hours, can still detect all the targeted organisms within 2 workdays using this cost effective strategy.

Background: Although EGFR inhibitors have shown some success in the treatment of head and neck squamous cell carcinomas (HNSCCs), the results are not dramatic. Additional molecular targets are urgently needed. We previously showed that the loss of Ron receptor activity significantly slowed squamous tumour growth and progression in a murine model. Based on these data, we hypothesised that Ron expression confers an aggressive phenotype in HNSCCs. We prospectively collected and evaluated 154 snap-frozen, primary HNSCCs for Ron and EGFR expression/phosphorylation. Biomarker correlation with clinical, pathological and outcome data was performed. The biological responses of HNSCC cell lines to Ron knockdown, its activation and the biochemical interaction between Ron and EGFR were examined., Results: We discovered that 64.3% (99 out of 154) HNSCCs expressed Ron. The carcinomas expressed exclusively mature functional Ron, whereas the adjacent nonmalignant epithelium expressed predominantly nonfunctional Ron precursor. There was no significant association between Ron and sex, tumour differentiation, perineural/vascular invasion or staging. However, patients with Ron+HNSCC were significantly older and more likely to have oropharyngeal tumours. Ron+HNSCC also had significantly higher EGFR expression and correlated strongly with phosphorylated EGFR (pEGFR). Newly diagnosed HNSCC with either Ron/pEGFR or both had lower disease-free survival than those without Ron and pEGFR. Knocking down Ron in SCC9 cells significantly blunted their migratory response to not only the Ron ligand, MSP, but also EGF. Stimulation of Ron in SCC9 cells significantly augmented the growth effect of EGF; the synergistic effect of both growth factors in SCC9 cells was dependent on Ron expression. Activated Ron also interacted with and transactivated EGFR., Conclusion: Ron synergises with EGFR to confer certain adverse features in HNSCCs.

A 6-year-old male presented with a testicular mass, hepatosplenomegaly, and a pleural effusion while undergoing maintenance chemotherapy for treatment of T-cell acute lymphoblastic leukemia (T-ALL). He was subsequently diagnosed with a lymphoproliferative disorder that resembled hepatosplenic lymphoma (HSL). While the extranodal presentation and the protracted yet aggressive clinical course are consistent with HSL, the findings of monosomy 8 and polymorphic cell populations are unique and have not been previously described in this type of lymphoma., (Copyright © 2013 Wiley Periodicals, Inc.)

We described the monetary and non-monetary cost incurred by children hospitalized for virologically confirmed influenza virus infection in a population-based prospective 3-year study. The mean direct and indirect cost of each child hospitalized was $1217.82 (95% CI, 1111.54-1324.23) and $1328.33 (95% CI, $1136.79-1520.00) for influenza A and B, respectively. School age patients took a mean (SD) of 4.70 (3.05) days and 5.31 (3.62) days of sick leave for influenza A and B infection, respectively. Pediatric influenza A and B hospitalization was associated with 662-1046 days of school absenteeism and 214-336 days of parental work loss per 10,000 population <18 years of age per year. We showed that the cost incurred by hospitalization alone, was comparable to the cost of annual universal pediatric influenza vaccination especially in children 6 months to under 6 years of age and vaccination would result in much larger cost-savings when non-monetary costs are included., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: A wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza., Methodology/major Findings: We conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome., Conclusion: Disease manifestation of children hospitalized for pH1N1 infection was mild in our patient population.

Epidermal growth factor receptor (EGFR) is a target in head and neck cancer. High EGFR expression and phosphorylated EGFR predicts poor survival in head and neck cancer patients, but does not correlate with advanced stage disease. The aim of this study is to determine if clinical biological correlates are more accurate when different aspects of EGFR are evaluated in combination. We analyzed the EGFR phosphorylation, expression, and mutations in 60 primary head and neck tumors. We not only found that head and neck tumors with either truncated or activated EGFR tend to have higher tumor and nodal stage but also discovered two novel EGFR truncations.

Objective: To compare three Clostridium difficile EIA kits for the detection of C. difficile toxins from clinical specimens., Design: A total of 287 fresh and stored stool specimens were tested using all three assays. Stools with discrepant results were sent to a reference laboratory for tissue cytotoxin assay., Setting: Trinity Medical Center, a community hospital with network hospitals., Patients: Patients with diarrhea submitted stools for detection of C. difficile toxins., Results: Of the 287 stool specimens, 116 were positive and 171 negative for C. difficile toxins. The sensitivity, specificity, and positive and negative predictive values of Meridian EIA assay were 99.1, 97.7, 96.6, and 99.4%; ImmunoCard were 100, 98.2, 97.5, and 100%; BioStar OIA assay were 94, 98.8, 98.2, and 96% respectively. ImmunoCardprovides the best sensitivity (100%) for C. difficile toxins A and B detection. The BioStar OIA rapid test missed seven positive stool specimens possibly due to failure to detect toxin B., Conclusion: ImmunoCard has slightly higher predictive values, shorter turnaround time and greater convenience compared to the Meridian EIA Assay. ImmunoCard may be cost effective not only in smaller laboratories, but also in high volume laboratories, when used on a STAT basis or single request.