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1.
Nurse Educ Today ; 144: 106399, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39299022

ABSTRACT

BACKGROUND AND AIM: Academic writing is essential to achieve success for doctoral students and is often linked to their academic identity, which could provoke negative emotions leading to the risk of burnout and dropping out of their studies. Although academic writing is a substantial part of doctoral students' learning journey, there are no existing recommendations to guide the provision of effective support addressing nursing and midwifery doctoral students' needs in academic writing. This review aims to identify the key considerations that could facilitate education facilities and educators to provide effective support for academic writing among nursing and midwifery doctoral students, fostering a supportive environment for guidance and development. DESIGN: The review team was co-led by two doctoral students and two academics with all the team members being doctoral students at the School of Nursing and Midwifery in a research-intensive university. Seven databases were searched in February 2022 with an updated search conducted in July 2023. This review was guided by the methodological framework for scoping reviews: PRISMA for Scoping Review Checklist and Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. A narrative synthesis was conducted to analyse the data. RESULTS: A total of 11 papers were included. Six key considerations for developing effective academic writing support were identified including modes of delivery; barriers to writing; accountability and productivity; building group identity, collegiality and a sense of community; peer review, and behavioural change in writing practice. CONCLUSIONS: Findings highlighted that both face-to-face and online writing support groups enhance doctoral students' motivation and confidence in writing. The opportunity of active engagement, sharing writing commitments and short bursts of writing practice is pivotal in promoting doctoral students' writing productivity and satisfaction resulting in a higher on-time completion rate. Future studies should focus on the nursing and midwifery students' educational needs in academic writing.

3.
BMC Nurs ; 22(1): 370, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37814245

ABSTRACT

BACKGROUND: Parkinson's Disease (PD) is a common neurological condition that often causes stiffness, tremor and slow movement. People living with PD are likely to encounter nursing students throughout their journey from pre-diagnosis to death. Despite this, there is a paucity of evidence about current practice in PD education amongst nursing students. The present study provides an evaluation of a co-designed Parkinson's Awareness audio podcast amongst nursing students in Northern Ireland. METHODS: Following co-design of an audio podcast about PD, a mixed methods evaluation was carried out. 332 student nurses completed pre-/post-test questionnaires about their knowledge and perceptions of PD before and after listening to the audio podcast. Further to this, 35 student nurses participated in focus-group interviews six months following listening to explore how the podcast influenced practice. RESULTS: Student nurses posted a mean score of 52% before listening to the audio podcast. This mean increased to 80% post-test. These findings were statistically significant (p < 0.001), demonstrating significant increases in PD awareness after listening. Findings from the focus groups suggested that the audio podcast improved empathy and practice towards people with PD. The findings also suggested that students perceived audio podcasts to be a good way to learn about PD. CONCLUSION: Provision of a co-designed audio podcast about PD has the potential to improve student nurse knowledge and practice related to PD as evidenced in this study.

4.
BMC Med Educ ; 23(1): 457, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340427

ABSTRACT

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.


Subject(s)
Interprofessional Education , Students, Health Occupations , Humans , Learning , Problem Solving , Universities , Interprofessional Relations , Attitude of Health Personnel
5.
Cancer Causes Control ; 34(10): 837-843, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37335392

ABSTRACT

PURPOSE: The incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown. METHODS: We compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978-2015 and diagnosed in 1988-2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models. We also assessed whether Ewing sarcoma clustered within families. RESULTS: Compared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03-0.18), Asian (OR = 0.57, 95% CI 0.41-0.80), and Hispanic (OR = 0.73, 95% CI 0.62-0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00-1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles. CONCLUSIONS: This population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.


Subject(s)
Sarcoma, Ewing , Female , Humans , Birth Weight , Ethnicity , Hispanic or Latino , Risk Factors , Sarcoma, Ewing/epidemiology , Sarcoma, Ewing/genetics , California/epidemiology , Black or African American , White , Asian
6.
Adv Health Sci Educ Theory Pract ; 28(1): 27-46, 2023 03.
Article in English | MEDLINE | ID: mdl-35943605

ABSTRACT

Examiners' judgements play a critical role in competency-based assessments such as objective structured clinical examinations (OSCEs). The standardised nature of OSCEs and their alignment with regulatory accountability assure their wide use as high-stakes assessment in medical education. Research into examiner behaviours has predominantly explored the desirable psychometric characteristics of OSCEs, or investigated examiners' judgements from a cognitive rather than a sociocultural perspective. This study applies cultural historical activity theory (CHAT) to address this gap in exploring examiners' judgements in a high-stakes OSCE. Based on the idea that OSCE examiners' judgements are socially constructed and mediated by their clinical roles, the objective was to explore the sociocultural factors that influenced examiners' judgements of student competence and use the findings to inform examiner training to enhance assessment practice. Seventeen semi-structured interviews were conducted with examiners who assessed medical student competence in progressing to the next stage of training in a large-scale OSCE at one Australian university. The initial thematic analysis provided a basis for applying CHAT iteratively to explore the sociocultural factors and, specifically, the contradictions created by interactions between different elements such as examiners and rules, thus highlighting the factors influencing examiners' judgements. The findings indicated four key factors that influenced examiners' judgements: examiners' contrasting beliefs about the purpose of the OSCE; their varying perceptions of the marking criteria; divergent expectations of student competence; and idiosyncratic judgement practices. These factors were interrelated with the activity systems of the medical school's assessment practices and the examiners' clinical work contexts. Contradictions were identified through the guiding principles of multi-voicedness and historicity. The exploration of the sociocultural factors that may influence the consistency of examiners' judgements was facilitated by applying CHAT as an analytical framework. Reflecting upon these factors at organisational and system levels generated insights for creating fit-for-purpose examiner training to enhance assessment practice.


Subject(s)
Education, Medical , Students, Medical , Humans , Judgment , Australia , Educational Measurement , Clinical Competence
7.
Phys Eng Sci Med ; 45(3): 915-924, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35925545

ABSTRACT

A helical fan-beam kilovoltage computed tomography (kVCT) was recently introduced into Tomotherapy units. This study aims to share the initial experience of kVCT in clinical workflow, compare its performance with that of the existing megavoltage computed tomography (MVCT), and explore its potential in adaptive planning. We retrospectively enrolled 23 patients who underwent both MVCT and kVCT scans. The clinical performance data regarding image acquisition time, nominal dose length product (DLP), registration time and registration corrections were extracted and compared. Image quality was scored by six experienced radiation therapists and quantified based on phantom measurements. CT number stability and the implementation of adaptive radiotherapy were dosimetrically evaluated by performing the dose recalculation on kVCT. Compared to MVCT, kVCT significantly reduced DLP (except the highest kVp protocol), image acquisition and registration time. KVCT obtained higher scores than MVCT on all criteria except artifacts. Phantom measurements also revealed a better image performance characterization of kVCT except for image uniformity. The CT number variation could lead to a dose difference of 0.5% for D95% of target and Dmean of organ-at-risk. For the treatment planning with kVCT, a systematic dose difference (> 1%) in PTV dose metrics was observed at regions with large longitudinal density discontinuities compared to the reference plans. The new kVCT imaging provides enhanced soft-tissue visualization. The improved efficiency with kVCT-guided treatment will allow more patients to be treated each day. In most cases, the dose calculation accuracy of kVCT images is acceptable except for regions with severe artifacts.


Subject(s)
Radiotherapy, Intensity-Modulated , Humans , Phantoms, Imaging , Retrospective Studies , Tomography, Spiral Computed/methods , Tomography, X-Ray Computed/methods
8.
Biotechniques ; 72(4): 121-133, 2022 04.
Article in English | MEDLINE | ID: mdl-35255733

ABSTRACT

DNA methylation is a labile modification associated with gene expression control and environmental adaptations. High throughput, scalable and quantitative assessments of specific DNA methylation modifications in complex genomic regions for use in large population studies are needed. The performance of Droplet Digital™ PCR (ddPCR™) was investigated for DNA methylation detection against next-generation bisulfite sequencing (NGS) to demonstrate the ability of ddPCR to detect and validate DNA methylation levels and complex patterns among neighboring CpGs in regions associated with prenatal tobacco exposure. While both techniques are reproducible, ddPCR demonstrates a unique advantage for high-throughput DNA methylation analysis in large-scale population studies and provides the specificity to accurately measure DNA methylation of target CpGs in complex regions.


Subject(s)
DNA Methylation , Nicotiana , CpG Islands , DNA Methylation/genetics , Genomics , High-Throughput Nucleotide Sequencing , Polymerase Chain Reaction/methods
9.
Med Teach ; 44(8): 914-921, 2022 08.
Article in English | MEDLINE | ID: mdl-35343380

ABSTRACT

INTRODUCTION: Examiners' professional judgements of student performance are pivotal to making high-stakes decisions to ensure graduating medical students are competent to practise. Clinicians play a key role in assessment in medical education. They are qualified in their clinical area but may require support to further develop their understanding of assessment practices. However, there are limited studies on providing examiners with structured feedback on their assessment practices for professional development purposes. METHODS: This study adopts an interpretive paradigm to develop an understanding of clinical examiners' interpretations of receiving structured feedback and its impacts on enhancing their assessment literacy and practice. Data were collected from 29 interviews with clinical examiners who assessed the final-year medical objective structured clinical examinations (OSCEs) at one university. RESULTS: Inductive thematic analysis of these data revealed that the examiners considered the feedback to be useful with practical functions in facilitating communication, comparisons and self-reflection. However, the examiners' level of confidence in the appropriateness of their assessment practices and difficulties in interpreting feedback could be barriers to adopting better practices. CONCLUSION: Feedback for examiners needs to be practical, targeted, and relevant to support them making accountable and defensible judgements of student performance.


Subject(s)
Education, Medical , Students, Medical , Clinical Competence , Educational Measurement , Feedback , Formative Feedback , Humans
10.
PLoS One ; 16(8): e0252282, 2021.
Article in English | MEDLINE | ID: mdl-34358226

ABSTRACT

Epilepsy is a complex neurological condition characterized by repeated spontaneous seizures and can be induced by initiating seizures known as status epilepticus (SE). Elaborating the critical molecular mechanisms following SE are central to understanding the establishment of chronic seizures. Here, we identify a transient program of molecular and metabolic signaling in the early epileptogenic period, centered on day five following SE in the pre-clinical kainate or pilocarpine models of temporal lobe epilepsy. Our work now elaborates a new molecular mechanism centered around Wnt signaling and a growing network comprised of metabolic reprogramming and mTOR activation. Biochemical, metabolomic, confocal microscopy and mouse genetics experiments all demonstrate coordinated activation of Wnt signaling, predominantly in neurons, and the ensuing induction of an overall aerobic glycolysis (Warburg-like phenomenon) and an altered TCA cycle in early epileptogenesis. A centerpiece of the mechanism is the regulation of pyruvate dehydrogenase (PDH) through its kinase and Wnt target genes PDK4. Intriguingly, PDH is a central gene in certain genetic epilepsies, underscoring the relevance of our elaborated mechanisms. While sharing some features with cancers, the Warburg-like metabolism in early epileptogenesis is uniquely split between neurons and astrocytes to achieve an overall novel metabolic reprogramming. This split Warburg metabolic reprogramming triggers an inhibition of AMPK and subsequent activation of mTOR, which is a signature event of epileptogenesis. Interrogation of the mechanism with the metabolic inhibitor 2-deoxyglucose surprisingly demonstrated that Wnt signaling and the resulting metabolic reprogramming lies upstream of mTOR activation in epileptogenesis. To augment the pre-clinical pilocarpine and kainate models, aspects of the proposed mechanisms were also investigated and correlated in a genetic model of constitutive Wnt signaling (deletion of the transcriptional repressor and Wnt pathway inhibitor HBP1). The results from the HBP1-/- mice provide a genetic evidence that Wnt signaling may set the threshold of acquired seizure susceptibility with a similar molecular framework. Using biochemistry and genetics, this paper outlines a new molecular framework of early epileptogenesis and advances a potential molecular platform for refining therapeutic strategies in attenuating recurrent seizures.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Epilepsy, Temporal Lobe/metabolism , Glycolysis , Hippocampus/metabolism , Status Epilepticus/metabolism , TOR Serine-Threonine Kinases/metabolism , Wnt Signaling Pathway , AMP-Activated Protein Kinases/genetics , Animals , Astrocytes/metabolism , Astrocytes/pathology , Disease Models, Animal , Epilepsy, Temporal Lobe/genetics , Hippocampus/pathology , Male , Mice , Mice, Knockout , Neurons/metabolism , Neurons/pathology , Status Epilepticus/genetics , TOR Serine-Threonine Kinases/genetics
11.
Elife ; 102021 06 22.
Article in English | MEDLINE | ID: mdl-34155975

ABSTRACT

Background: The role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups. Methods: We used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity. Results: Given probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85-3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56-8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82-6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36-13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26-14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62-4.20). Conclusions: The data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States. Funding: This work was supported by the V Foundation for funding this work (Grant FP067172).


Subject(s)
Black People/statistics & numerical data , Ethnicity/statistics & numerical data , Genetic Predisposition to Disease/epidemiology , Hispanic or Latino/statistics & numerical data , Minority Groups/statistics & numerical data , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Neoplasms/epidemiology , Adolescent , Adult , California/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Risk Factors , Young Adult
12.
Nurse Educ Today ; 95: 104580, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33065526

ABSTRACT

OBJECTIVES: To explore how undergraduate health care students use digital technology to deliver patient care during their clinical placements. DESIGN: A scoping review of primary research was conducted using the extended PRISMA guidelines. DATA SOURCES: A subject specialist librarian assisted in searching for the academic literature in four electronic databases: CINAHL, PubMed, Scopus and ERIC. REVIEW METHODS: Four reviewers, working in pairs, independently reviewed a total of 332 potentially relevant articles according to set inclusion and exclusion criteria. Then, all included papers underwent an independent quality review by two reviewers. RESULTS: Seven studies involving medical or nursing/midwifery students were included in the review. Three studies evaluated the use of mobile learning devices in patient care with four studies evaluating the use of digital systems in practice. Due to the heterogeneity of studies, which used differing digital systems and instruments, the researchers decided the most suitable method of analysis was a narrative review. The results are explained using four key themes: student learning needs when using technology in practice; access to technology in placements; perceptions of using technology in placements; and impact of technology on patient care. CONCLUSION: The use of digital systems in clinical settings creates challenges and benefits to student learning in delivering patient care. When students are prepared and facilitated to use digital systems, a sense of confidence and belonging to the team is fostered. Lack of availability and access to these systems, however, may impede students' ability to be involved in all aspects of patient care. Limitations of the current review included the relatively low quality of the educational research being conducted in this field of research. Further quality research is needed to explore how students in the health care professions are supported in digital environments and how higher education institutions are adapting their curricula to meet the digital learning needs of health care students.


Subject(s)
Digital Technology , Students, Nursing , Curriculum , Delivery of Health Care , Humans , Patient Care
13.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1162-1167, 2020 06.
Article in English | MEDLINE | ID: mdl-32245786

ABSTRACT

BACKGROUND: Synovial sarcoma is a rare cancer with peak incidence in the young adult period. Despite poor outcomes of this aggressive cancer, there is little epidemiologic research addressing its etiology. METHODS: We collected birth characteristic data on synovial sarcoma cases born during 1978-2015 and diagnosed during 1988-2015 in California (n = 244), and 12,200 controls frequency-matched on year of birth. We also constructed a dataset of cancer cases in siblings of sarcoma subjects to assess familial risk. RESULTS: In multivariable logistic regression analyses, synovial sarcoma was more frequent in Hispanics compared with non-Hispanic whites [OR, 1.48; 95% confidence interval (CI), 1.06-2.08]. Higher birth weight was a risk factor in Hispanics; each 500 g increase in birth weight was associated with a 22% increase in disease risk (OR, 1.22; 95% CI, 1.00-1.48). Also, a strong role for birth order was suggested, with highest risk for the first born (second child compared with first: OR, 0.61; 95% CI, 0.44-0.84; third or later compared with first: OR, 0.53; 95% CI, 0.36-0.77). Siblings of patients with synovial sarcoma did not display elevated cancer incidence, suggesting the low likelihood that strong familial predisposition alleles play a significant role in this disease. CONCLUSIONS: The associations with birth weight and birth order suggest that nutritional, developmental, and environmental factors may play a role in the etiology of synovial sarcoma. IMPACT: Further epidemiologic research on synovial sarcoma should evaluate epigenetic and developmental mechanisms and the formation of the archetypical t(X;18) translocation that defines this disease.


Subject(s)
Birth Order , Sarcoma, Synovial/genetics , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Risk Factors , Sarcoma, Synovial/physiopathology , Young Adult
15.
Lab Anim (NY) ; 48(9): 247, 2019 09.
Article in English | MEDLINE | ID: mdl-31435037
16.
Science ; 363(6432): 1142-1143, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30872503
17.
Brachytherapy ; 18(2): 171-179, 2019.
Article in English | MEDLINE | ID: mdl-30581053

ABSTRACT

BACKGROUND: Paradigm has shifted from 2D to image-guided adaptive brachytherapy (IGABT) for locally advanced cervix cancer (LACC). Increasing reports from pioneering institutions and large retrospective multicenter series have demonstrated improvements in outcome and reduction in toxicity with IGABT. However, there is scarcity of data on magnetic resonance (MR)-IGABT in Chinese patients. PURPOSE: To evaluate the clinical outcome of MR-IGABT for LACC in a single institution in Hong Kong. MATERIAL AND METHODS: Patients with FIGO stage IB-IVA LACC treated with definitive external beam radiotherapy +/- concurrent cisplatin followed by MR-IGABT from January 2015 to January 2018 were included. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Dosimetric and clinical outcomes including local control (LC), pelvic control (PC), cancer-specific survival, overall survival (OS), and toxicity were analyzed. RESULTS: Forty-two consecutive patients were included. 71% were FIGO stage IIB or above; 52% had pelvic node involvement. Median high-risk clinical target volume (HRCTV) was 34.7 cm3 (12.3-155.1 cm3). Median dose to HRCTV D90 was 88.5 Gy (63.4-113.4 Gy) (EQD210). Median doses to the D2cc of bladder, rectum, sigmoid, and small bowel were 83.1 Gy, 67.5 Gy, 69.0 Gy, and 68.9 Gy (EQD23), respectively. Median followup was 20.3 months (4.0-35.1 months). 24-month actuarial LC, PC, cancer-specific survival, and OS were 90%, 84%, 90%, and 90%, respectively. Stratification by clinical variables showed that FIGO stage had significant impact on LC and dose to HRCTV on both LC and PC. Treatment was well tolerated without any severe late toxicity. CONCLUSIONS: Intermediate-term results from systematic MR-IGABT for LACC demonstrate very promising outcomes with minimal toxicity. This fills the gap in evidence for MR-IGABT in Chinese patients.


Subject(s)
Brachytherapy/methods , Magnetic Resonance Imaging , Radiotherapy, Image-Guided , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Brachytherapy/adverse effects , Cisplatin/therapeutic use , Colon, Sigmoid , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Organs at Risk , Pelvis , Radiation Dosage , Radiotherapy Dosage , Rectum , Retrospective Studies , Survival Rate , Treatment Outcome , Urinary Bladder , Uterine Cervical Neoplasms/pathology
18.
Asian Pac J Cancer Prev ; 19(12): 3551-3555, 2018 Dec 25.
Article in English | MEDLINE | ID: mdl-30583682

ABSTRACT

Background: Malignancies are among the leading causes of death in Systemic Lupus Erythematosus (SLE) patients with studies reporting a higher prevalence of malignancy in SLE patients compared to the general population. We wanted to determine the frequency of cancer in a cohort of SLE patients and identify its associated risk factors. Methods: Cross-sectional study involving SLE patients attending the nephrology outpatient clinic, Universiti Kebangsaan Malaysia Medical Centre between January and June 2014. Results: We recruited 228 patients (207 female, 21 male), aged 40.48 ± 12.86 years with mean SLE duration of 11.65 ± 6.46 years. Majority (87%) had lupus nephritis and were in remission with a median SLEDAI score 2 (0, 14). Majority (89%) were on corticosteroid with either a steroid sparing agent like mycophenolate mofetil (15.4%), azathioprine (36.8%) or ciclosporin (15.4%). One hundred and sixty (70.2%) patients were either receiving or had received intravenous cyclophosphamide with median dose of 5,173.6 ± 3,242.4 mg. Seven female patients were diagnosed with cancer during the course of their SLE with 56 (34-78) years being median age at malignancy and SLE duration of 4 (0-12) years. Majority (5/7) had lupus nephritis and all patients a median dose of prednisolone 10 (2.5, 10) mg with 10 (4-24) years of steroids. Two patients had a family history of cancer with majority developing cancer after the diagnosis of SLE. Two patients received intravenous cyclophosphamide prior to the development of cancer for their SLE compared to overall cohort of 160. Three patients had colorectal cancer, 2 had cervical cancer, 1 had breast cancer, and one patient had germ cell tumour and one thyroid cancer. All patients had their cancer successful treated with no signs of recurrence. Conclusion: We found a lower occurrence of cancer in our SLE patients as compared with the reported literature.


Subject(s)
Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/pathology , Neoplasms/etiology , Neoplasms/pathology , Adrenal Cortex Hormones/therapeutic use , Adult , Cohort Studies , Cross-Sectional Studies , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Malaysia , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/pathology , Prevalence , Risk Factors , Severity of Illness Index , Steroids/therapeutic use , Time Factors
19.
Lancet ; 391(10124): 923-924, 2018 03 10.
Article in English | MEDLINE | ID: mdl-29536846
20.
Neurobiol Dis ; 98: 149-157, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27852007

ABSTRACT

Infantile spasms (IS) are a catastrophic childhood epilepsy syndrome characterized by flexion-extension spasms during infancy that progress to chronic seizures and cognitive deficits in later life. The molecular causes of IS are poorly defined. Genetic screens of individuals with IS have identified multiple risk genes, several of which are predicted to alter ß-catenin pathways. However, evidence linking malfunction of ß-catenin pathways and IS is lacking. Here, we show that conditional deletion in mice of the adenomatous polyposis coli gene (APC cKO), the major negative regulator of ß-catenin, leads to excessive ß-catenin levels and multiple salient features of human IS. Compared with wild-type littermates, neonatal APC cKO mice exhibit flexion-extension motor spasms and abnormal high-amplitude electroencephalographic discharges. Additionally, the frequency of excitatory postsynaptic currents is increased in layer V pyramidal cells, the major output neurons of the cerebral cortex. At adult ages, APC cKOs display spontaneous electroclinical seizures. These data provide the first evidence that malfunctions of APC/ß-catenin pathways cause pathophysiological changes consistent with IS. Our findings demonstrate that the APC cKO is a new genetic model of IS, provide novel insights into molecular and functional alterations that can lead to IS, and suggest novel targets for therapeutic intervention.


Subject(s)
Adenomatous Polyposis Coli Protein/deficiency , Disease Models, Animal , Neurons/metabolism , Seizures/metabolism , Spasms, Infantile/metabolism , beta Catenin/metabolism , Adenomatous Polyposis Coli Protein/genetics , Animals , Animals, Newborn , Cerebral Cortex/growth & development , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Electroencephalography , Excitatory Postsynaptic Potentials/physiology , Female , Humans , Infant , Male , Mice, Knockout , Movement/physiology , Neurons/pathology , Phenotype , Seizures/pathology , Signal Transduction , Spasms, Infantile/pathology , Tissue Culture Techniques
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