Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study.

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. CONCLUSIONS: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

OBJECTIVE: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. SETTING: Five public hospitals in Hong Kong. PATIENTS: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. MAIN OUTCOME MEASURES: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. RESULTS: Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. CONCLUSIONS: Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

Cytogenetic biodosimetry: what it is and how we do it.

Dicentric assay is the international gold standard for cytogenetic biodosimetry after radiation exposure, despite being very labour-intensive, time-consuming, and highly expertise-dependent. It involves the identification of centromeres and structure of solid-stained chromosomes and the enumeration of dicentric chromosomes in a large number of first-division metaphases of cultured T lymphocytes. The dicentric yield is used to estimate the radiation exposure dosage according to a statistically derived and predetermined dose-response curve. It can be used for population triage after large-scale accidental over-exposure to ionising radiation or with a view to making clinical decisions for individual patients receiving substantial radiation. In this report, we describe our experience in the establishment of a cytogenetic biodosimetry laboratory in Queen Elizabeth Hospital, Hong Kong. This was part of the contingency plan for emergency measures against radiation accidents at nuclear power stations.

Intrarenal Pressure Measured Using a Novel Flexible Ureteroscope with Pressure Sensing Capabilities: A Study of the Effects of Ureteral Access Sheath, Irrigation, and Working Channel Accessories.

Introduction: Intrarenal pressure is emerging as an important monitoring parameter during flexible ureteroscopy (fURS). We measure how intraoperative conditions affect intrarenal pressure using a novel pressure sensing ureteroscope. Methods: The LithoVue Elite (LVE) single-use digital flexible ureteroscope (Boston Scientific) is the first commercial ureteroscope that senses pressure at its tip. LVE was used in a porcine model to measure intrarenal pressure with and without a ureteral access sheath (UAS) with various sizes and placement locations, irrigation methods, and working channel accessories. LVE pressure accuracy was measured in a bench model. This abstract shows the least-square means from multiway analysis of variances used for analysis. Results: Intrarenal pressures were the highest without a UAS (64 mm Hg), followed by the 11/13 UAS (51 mm Hg) and the 12/14 and 13/15, which were not statistically different (39-40 mm Hg). The pressures were highest with UASs placed at the ureteropelvic junction (61 mm Hg), and lowest if placed in the renal pelvis (24 mm Hg). Irrigation methods showed the highest pressures with syringe (57 mm Hg), while irrigation bags (pressurized at 150-300 mm Hg) produced 43 to 46 mm Hg and 25 mm Hg when applied with 80 cm of gravity. Placing a 200 µm laser fiber reduced pressures from 44 to 41 mm Hg. Finally, the bench model showed that LVE was 96% accurate up to 300 mm Hg. Conclusion: Intrarenal pressure significantly varied based on UAS sizes, placement, and irrigation methods. Accordingly, fURS with LVE is poised to be an invaluable tool for clinical decision-making and future studies of intrarenal pressure.

Long-term follow-up on dusting versus basketing during ureteroscopy: a prospective multicenter trial from the EDGE Research Consortium.

In 2018, the Endourology Disease Group for Excellence (EDGE) published a prospective trial comparing dusting versus basketing during ureteroscopy. One hundred fifty-nine patients were included in the original analysis, which found no difference in stone-free rate at 3 months. We report the intermediate and long-term outcomes of patients included in the original trial. Two analyses were performed. At 1-year, a retrospective chart review was performed, and data collected on stone episodes, Emergency Department (ED) visits, hospital admissions and surgical interventions. To obtain long-term outcomes, the four sites with the largest initial accrual were included in a second phase of data collection with updated analyses. The patients from those sites were contacted, re-consented, and data were collected on stone surgical interventions, stone episodes, stone recurrences on imaging, emergency department (ED) visits, and hospital admissions for stone-related care since their original procedure. One-year follow-up data were collected in 111 of the original 159 (69.8%) patients from the nine sites. There were no statistically significant differences in the number of painful episodes, ED visits, hospital admissions, or surgical interventions. 94 patients from four sites were included in the long-term analysis. There were no statistically significant differences in surgical interventions, painful stone episodes, stone recurrence on imaging, ED visits or hospitalizations for stone-related events between the two groups. Long-term outcomes of dusting versus basketing during ureteroscopy indicate that there are no significant differences in clinical outcomes between the two surgical modalities.

A morpho-molecular prognostic model for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third common cause of cancer-related deaths and its prognostication is still suboptimal. The aim of this study was to establish a new prognostication algorithm for HCC. METHODS: In all, 13 biomarkers related to the etiopathogenesis of HCC were evaluated by immunohistochemistry using tissue microarrays containing 121 primary HCC resection cases, and validated in subsequent cohort of 85 HCC cases. The results were compared with Affymetrix Gene Chip Human Genome U133Plus microarray data in a separate cohort of 228 HCC patients. RESULTS: On immunohistochemical evaluation and multivariate Cox regression analysis p53, alpha fetaprotein (AFP), CD44 and CD31, tumour size and vascular invasion, were significant predictors for worse survival in HCC patients. A morpho-molecular prognostic model (MMPM) was constructed and it was a significant independent predictor for overall survival (OS) and relapse-free survival (RFS) (P<0.000). The OS and RFS of HCC(low) was higher (104 and 78 months) as compared with HCC(high) (73 and 43 months) (P<0.000 for OS and RFS). Hepatocellular carcinoma patients with higher stage (III+IV), >5 cm tumour size, positive vascular invasion and satellitosis belonged to HCC(high) group. The validation group reproduced the same findings. Gene expression analysis confirmed that 7 of the 12 biomarkers were overexpressed in >50% of tumour samples and significant overexpression in tumour samples was observed in AFP, CD31, CD117 and Ki-67 genes. CONCLUSION: The MMPM, based on the expression of selected proteins and clinicopathological parameters, can be used to classify HCC patients between good vs poor prognosis and high vs low risk of recurrence following hepatic resection.

Virtual blood banking in Hong Kong.

OBJECTIVE. To review our experience in virtual blood banking for intra-operative transfusion in Hong Kong. DESIGN. Retrospective study. SETTING. Three major acute hospitals and a specialised centre for joint replacement surgery with installation of an Operating Theatre Blood Transaction System. PATIENTS. Patients undergoing surgery under anaesthesia and requiring intra-operative transfusion for the period from the implementation of the system in individual institutes (Queen Elizabeth Hospital: June 1997; Princess Margaret Hospital: May 2001; Queen Mary Hospital: October 2009; and Hong Kong Buddhist Hospital: December 2010) till September 2011. RESULTS. Under the system, 58 923 units of red cells were released intra-operatively for 18 264 patients (11% of the total number of blood units issued by the blood banks in these institutes during the study period). About 1% of them (613 units) entailed unmatched red cells given to 183 patients for emergency transfusions during surgery. The mean time required for the issue of the first unit of red cells was less than 1 minute. A total of 1231 units of red cells were returned unused after being released. Among them, 95 units were deemed unfit for re-issue because they had left the temperature-monitored blood storage refrigerators in the operating theatres for more than 30 minutes. There was no delay in transfusion or postponement of surgery due to problems or downtime of the Operating Theatre Blood Transaction System. CONCLUSION. Our experience has shown that our virtual blood banking system was efficient and effective, and helped ensure that the right patient received the right amount of the right blood at the right time. The system can be implemented either locally in the same hospital with a central blood bank, or in a more remote and networked site without a nearby supporting blood bank.

Spatio-temporal correlations from fMRI time series based on the NN-ARx model.

For the purpose of statistical characterization of the spatio-temporal correlation structure of brain functioning from high-dimensional fMRI time series, we introduce an innovation approach. This is based on whitening the data by the Nearest-Neighbors AutoRegressive model with external inputs (NN-ARx). Correlations between the resulting innovations are an extension of the usual correlations, in which mean-correction is carried out by the dynamic NN-ARx model instead of the static, standard linear model for fMRI time series. Measures of dependencies between regions are defined by summarizing correlations among innovations at several time lags over pairs of voxels. Such summarization does not involve averaging the data over each region, which prevents loss of information in case of non-homogeneous regions. Statistical tests based on these measures are elaborated, which allow for assessing the correlation structure in search of connectivity. Results of application of the NN-ARx approach to fMRI data recorded in visual stimuli experiments are shown. Finally, a number of issues related with its potential and limitations are commented.

The establishment of an integrated skills training centre for undergraduate nursing education.

AIM: This paper details the experience of establishing an integrated skills training centre for use in undergraduate nursing education in The Open University of Hong Kong. BACKGROUND: Skills training is an essential element in undergraduate nursing education. Owing to the increasing complexity of the health-care system and patient health needs, undergraduate nursing students should be well prepared for integrated skills competency, critical thinking and rapid decision-making. To achieve this goal, the use of simulation as a skills training tool is being recommended. CONCLUSION: The Clinical Nursing Education Centre is established. It adopts simulation as a teaching and learning tool. It has four specific education units, namely: (1) clinical simulation education unit, (2) virtual reality education unit, (3) nursing skills education unit, and (4) Chinese medicinal education unit. These units are specifically designed for the teaching and learning of nursing skills related to general, mental and Chinese medicinal nursing from elementary to advanced level. Experiences pertaining to the conceptualization, exploration and actualization phases of the establishment are presented. Details of the structure and specific functions of the centre are also illustrated. Finally, there is discussion on the challenges encountered during the establishment process and how they were overcome.

Hong Kong enrolled nurses' perceptions of spirituality and spiritual care.

AIM: To explore Hong Kong nurses' perceptions of spirituality and spiritual care, and to investigate the relationship between their perceptions and their demographic characteristics. BACKGROUND: Many studies suggest that spirituality is the essence of human being and plays an important role in people's lives. Although studies have documented the positive relationship between spiritual care and patients' health outcomes, it has also been shown that the implementation of spiritual care is uncommon in nursing practice. Furthermore, there is little discussion on practising nurses' perception of spirituality and spiritual care in Hong Kong. METHODS: This study adopted a cross-sectional descriptive design to investigate nurses' perception of spirituality and spiritual care in Hong Kong. A convenience sample of 429 practising enrolled nurses were invited to complete the Spirituality and Spiritual Care Rating Scale (SSCRS) (response rate 91%). FINDINGS: Subjects showed satisfactory understanding of spirituality and appreciated providing spiritual care to patients. The mean scores for the SSCRS and its four subscales were greater than half of the maximum score. There were significant differences in the perceptions of spirituality between subjects with different education levels and religious affiliations. CONCLUSIONS: The findings suggest increasing the emphasis of spirituality both in undergraduate education and in continuing-development levels. Recommendations are also made regarding the implementation of spiritual care in nursing practice. Despite having a convenience sample, the present study has contributed to stimulating awareness and discussion among nurses on spirituality and spiritual care.

Transformed follicular lymphoma with concurrent t(2;3), t(8;14) and t(14;18).

An elderly Chinese man who had an 8-year history of follicular lymphoma presented with large B-cell lymphoma. The disease ran a rapidly fatal course with a terminal leukemic phase. Cytogenetic analysis of the transformed follicular lymphoma showed a complex karyotype of 48,Y,t(X;19)(q26;p13.3),t(2;3)(p12;q27),t(8;14)(q24.1;q32),+12,t(14;18)(q32;q21),+21. To my knowledge, this is the first reported case of simultaneous occurrence of t(2;3), t(8;14), and t(14;18) in transformed follicular lymphoma.

Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia.

The Wnt pathway has been shown recently, to be activated in patients with chronic lymphocytic leukemia (CLL). This is the first study to examine the role of Wnt inhibitory factor-1 (Wif-1) methylation in the pathogenesis of haematolymphoid malignancies. Wif-1, a putative tumor suppressor, is a soluble negative regulator of the Wnt pathway activated in CLL. We studied the role of methylation of Wif-1 in 43 Chinese patients with CLL. At diagnosis, Wif-1 methylation was detected in 5/43 (11.6%) CLL marrow samples. Wif-1 methylation occurred more frequently in patients with advanced age (p = 0.059) but there was no correlation between Wif-1 methylation and sex, lymphocyte count and Rai stage at diagnosis. In conclusion, Wif-1 is infrequently methylated in CLL. Other factors leading to activation of the Wnt pathway warrant further study.

Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients.

BACKGROUND: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2, respectively. AIM: To study the role of methylation in the inactivation of CKI in chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Methylation-specific polymerase chain reaction was carried out on DNA obtained from the bone marrow of 56 newly diagnosed patients with CLL. RESULTS: Similar demographic features and clinical outcome were observed in our patients when compared with Caucasian patients, including an indolent clinical course (10-year overall survival 51%) and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12 and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%) CLL samples harboured concurrent methylation of both p15 and p16. Apart from an association of p16 methylation with higher presenting leucocyte count (64.5 x 10(9)/l in methylated p16 and 16.0 x 10(9)/l in unmethylated p16 patients; p = 0.016), there was no association between p15 and p16 methylation and age, sex and Rai stage. No difference was observed in the overall survival for patients with and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4 (7.1%) patients, methylation of p21 and p27 was uniformly absent. CONCLUSION: p15 and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP family, were targeted by methylation in CLL. p16 methylation was associated with a higher lymphocyte count at presentation. This is the first comprehensive study of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in Chinese patients with CLL.

Isochromosome 7q in Down syndrome.

Isochromosome 7q is not an uncommon chromosomal abnormality. It has been reported in association with Shwachman-Diamond syndrome, Wilms tumor, and hepatosplenic T-cell lymphoma. In other hematolymphoid malignancies, it occurs almost invariably as a secondary change. A notable example is its association with t(4;11)(q21;q23) in acute lymphoblastic leukemia. It has rarely been described in myelodysplastic syndrome and acute myeloid leukemia. We report the occurrence of i(7q) as the primary abnormality in a 2-year-old boy with Down syndrome and minimally differentiated acute myeloid leukemia.

Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population.

The -308 GA promoter polymorphism of tumor necrosis factor alpha (TNFalpha) has been reported to be associated with an increased risk of lymphoid malignancies in Caucasians. We studied the incidence and prognostic significance of this polymorphism in Chinese patients with plasma cell myeloma (PCM), chronic lymphocytic leukemia (CLL) and lymphomas. Despite a far lower incidence of PCM and CLL in the Chinese population compared with Caucasians, the rates of TNFalpha-308A were similar to those in Caucasians, both in the study and control populations. Similarly, there was no increased rate of TNFalpha-308A in all the lymphomas studied, irrespective of lineage. However, TNFalpha-308A is significantly associated with female CLL cases and confers a strong negative prognostic impact for Chinese CLL. These argue for a possible biological role for increased TNFalpha production in CLL progression in low-risk individuals.

Aberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemia.

The retinoic acid receptor alpha (RARA) gene is disrupted by PML/RARA fusion in acute promyelocytic leukemia (APL). The P2 promoter of RARA, controlling the RARalpha2 isoform, contains an RA-responsive element and may be targeted in APL. To test whether aberrant methylation of P2 was involved, 47 APL at diagnosis, 16 APL at first relapse, 50 acute myeloid leukemia (AML) and 22 acute lymphoblastic leukemia (ALL) were tested by methylation-specific polymerase chain reaction. RARA P2 methylation was highly associated with APL (APL: 25/63 vs AML/ALL: 2/75, P<0.0001). P2 methylation occurred at similar frequencies in APL at diagnosis and relapse, suggesting it was an initiating leukemogenic event. In the APL line NB4, RARalpha2 was not expressed, with the untranslocated RARA shown to be P2 methylated. 5-Azacytadine treatment of NB4 led to progressive P2 demethylation and re-expression of RARalpha2, confirming that RARA methylation collaborated with PML/RARA in totally suppressing RARalpha. In APL, RARA P2 methylation was unrelated to gender, age, presenting leukocyte counts and additional cytogenetic aberrations. For APL patients receiving all-trans retinoic acid for induction, P2 methylation did not affect the complete remission rates and survivals. RARA is the first myeloid-specific transcription factor shown to be dysregulated by both translocation and aberrant methylation.

Collaborative Evaluation of the Healthy Habits Program: An Effective Community Intervention to Improve Mobility and Cognition of Chinese Older Adults Living in the U.S.

OBJECTIVES: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons. DESIGN, SETTING AND PARTICIPANTS: Quantitative evaluation was performed on 50 Chinese older adults enrolled in the HHP. The community members were trained in data collection and management. MEASUREMENTS: Cognition (Mini Mental State Examination (MMSE), Trail Making Test and Complex Walking Task), mobility (Short Physical Performance Battery (SPPB) and maximal gait speed), depressive symptoms (Patient Health Questionnaire-9), perceived disability (World Health Organization Disability Assessment 2.0), nutritional status (Mini Nutrition Assessment®), and strength (grip and leg strength) were assessed at baseline and at 6 months. All tests were translated into Chinese. RESULTS: Of the 50 participants (mean age 68.4 years; 68% female), 78% achieved the goal of performing exercise ≥3 times/week. After 6 months, clinically meaningful improvements were observed in mobility (mean SPPB score changed from 10.3 to 11.1 points; p=0.01) and cognition (mean MMSE score changed from 26.0 to 27.8 points; p=0.001). There were also statistically significant improvements in executive function, depressive symptoms and perceived disability (p<0.05). CONCLUSION: Culturally sensitive community interventions, such as the HHP, are effective for improving mobility and cognition of Chinese older adults. This reveals the potential of promoting successful aging in minority populations through community settings, and should be advocated to reduce ethnic health disparities in the U.S.

Evaluation of the user seal check on gross leakage detection of 3 different designs of N95 filtering facepiece respirators.

BACKGROUND: The use of N95 respirators prevents spread of respiratory infectious agents, but leakage hampers its protection. Manufacturers recommend a user seal check to identify on-site gross leakage. However, no empirical evidence is provided. Therefore, this study aims to examine validity of a user seal check on gross leakage detection in commonly used types of N95 respirators. METHODS: A convenience sample of 638 nursing students was recruited. On the wearing of 3 different designs of N95 respirators, namely 3M-1860s, 3M-1862, and Kimberly-Clark 46827, the standardized user seal check procedure was carried out to identify gross leakage. Repeated testing of leakage was followed by the use of a quantitative fit testing (QNFT) device in performing normal breathing and deep breathing exercises. Sensitivity, specificity, predictive values, and likelihood ratios were calculated accordingly. RESULTS: As indicated by QNFT, prevalence of actual gross leakage was 31.0%-39.2% with the 3M respirators and 65.4%-65.8% with the Kimberly-Clark respirator. Sensitivity and specificity of the user seal check for identifying actual gross leakage were approximately 27.7% and 75.5% for 3M-1860s, 22.1% and 80.5% for 3M-1862, and 26.9% and 80.2% for Kimberly-Clark 46827, respectively. Likelihood ratios were close to 1 (range, 0.89-1.51) for all types of respirators. CONCLUSIONS: The results did not support user seal checks in detecting any actual gross leakage in the donning of N95 respirators. However, such a check might alert health care workers that donning a tight-fitting respirator should be performed carefully.