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  1. Said Z, Murdoch C, Hansen J, Siim Madsen L, Colley HE
    Eur J Oral Sci, 2021 04;129(2):e12761.
    PMID: 33645844 DOI: 10.1111/eos.12761
    Oral lichen planus (OLP) is an immune-mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T-cells, to examine corticosteroid potency and delivery of clobetasol-17-propionate from a novel electrospun mucoadhesive patch. The OMEs displayed tight junctions, desmosomes, hemidesmosomes, and an efficient permeability barrier. Following application of corticosteroids to cells cultured as monolayers, the degree of cytotoxicity measured correlated to the level of potency recognized for each corticosteroid; by contrast, OMEs were largely unaffected by corticosteroid treatment. Permeation of clobetasol-17-propionate into and through the OMEs was time- and dose-dependent, regardless of whether this corticosteroid was delivered in liquid form or from a mucoadhesive patch, and both liquid- and patch-delivered clobetasol-17-propionate significantly reduced the secretion of interleukin-2 by activated T-cells. This study confirms that OMEs are more suitable models than cell monolayers for evaluating toxicity and drug delivery. After topical exposure, clobetasol-17-propionate accumulated in OMEs at a higher level than betamethasone-17-valerate and hydrocortisone-17-valerate, and exerted its immunosuppressive actions following application via the patch delivery system, highlighting the efficacy of this mode of drug delivery to treat OLP.
  2. Jan Mohamed HJ, Yap RW, Loy SL, Norris SA, Biesma R, Aagaard-Hansen J
    Asia Pac J Public Health, 2015 Mar;27(2):123-35.
    PMID: 25524952 DOI: 10.1177/1010539514562447
    This systematic review aimed to examine trends in overweight, obesity, and type 2 diabetes mellitus (T2DM) among Malaysian adults, and to identify its underlying determinants. A review of studies published between 2000 and 2012 on overweight, obesity, and T2DM was conducted. The Cochrane library of systematic reviews, MEDLINE, EMBASE, Biosis, Scopus, and MyJurnal digital database were searched. According to national studies, the prevalence of overweight increased from 26.7% in 2003 to 29.4% in 2011; obesity prevalence increased from 12.2% in 2003 to 15.1% in 2011, and T2DM prevalence was reported as 11.6% in 2006 and 15.2% in 2011. Distal determinants of increased risk of overweight, obesity, and T2DM were as follows: female, Malay/Indian ethnicity, and low educational level. The limited number of studies on proximal determinants of these noncommunicable diseases (NCDs) indicated that an unhealthy diet was associated with increased risk, whereas smoking was associated with decreased risk. However, more studies on the proximal determinants of overweight, obesity, and T2DM within the Malaysian context are needed. Overall, our findings provide insights for designing both future investigative studies and strategies to control and prevent these NCDs in Malaysia.
  3. Lim SC, Mustapha FI, Aagaard-Hansen J, Calopietro M, Aris T, Bjerre-Christensen U
    Med Educ Online, 2020 Dec;25(1):1710330.
    PMID: 31891330 DOI: 10.1080/10872981.2019.1710330
    Background: Continuing Medical Education (CME) is a cornerstone of improving competencies and ensuring high-quality patient care by nurses and physicians. The Ministry of Health (MOH) Malaysia collaborated with Steno Diabetes Centre to improve diabetes-related competencies of general physicians and nurses working in primary care through a six-month training programme called the Steno REACH Certificate Course in Clinical Diabetes Care (SRCC).Objective: This impact evaluation aimed to assess the effect of participation of general physicians and nurses in the SRCC in selected public primary healthcare clinics in Kuala Lumpur and Selangor, Malaysia.Design: The quasi-experimental, embedded, mixed-methods study used concurrent data collection and the Solomon four-group design. Participants in an intervention group (Arm 1) and control group (Arm 3) were assessed by pre-and post-test, and participants in separate intervention (Arm 2) and control (Arm 4) groups were assessed by post-test only. Quantitative and qualitative methods were used to assess the effect of the programme.Results: Thirty-four of the 39 participants in the intervention groups (Arms 1 and 2) completed the SRCC and were included in the analysis. All 35 participants in the control groups (Arms 3 and 4) remained at the end of the study period. Significant improvements in diabetes-related knowledge, skills and clinical practise were found among general physicians and nurses in the intervention group after the six-month SRCC, after controlling the pretest effects. No clear changes could be traced regarding attitudes.Conclusion: SRCC participants had significant improvements in knowledge, skills and clinical practice that meet the current needs of general physicians and nurses working in primary care in Malaysia. Thus, SRCC is an effective CME approach to improving clinical diabetes care that can be scaled up to the rest of the country and, with some modification, beyond Malaysia.
  4. Mustapha FI, Aagaard-Hansen J, Lim SC, Nasir NH, Aris T, Bjerre-Christensen U
    Health Serv Res Manag Epidemiol, 2020 04 15;7:2333392820918744.
    PMID: 32313820 DOI: 10.1177/2333392820918744
    Background: The article describes variations in the organization of clinical services for diabetes patients in 10 public primary health clinics in Malaysia with the view to learn from current innovations and improve diabetes service provision.

    Methods: This study combined the use of secondary data and a qualitative multicase study approach applying observations in 10 randomly selected Ministry of Health (MOH) health clinics in Kuala Lumpur and Selangor and semistructured interviews of the family medicine specialists from the same clinics.

    Results: Although there are specific MOH guidelines for diabetes care, some clinics had introduced innovations for diabetes care such as the novel 'personalized care', 'one-stop-centre' and utilization of patients' waiting time for health education. Analysis showed that there was room for improvement in terms of task shifting to free precious time of staff with specialized functions, streamlining appointments for various examinations, increasing continuity of consultations with same doctors, and monitoring of performance.

    Conclusion: We contend that there is a potential for increased effectiveness and efficiency of primary diabetes care in Malaysia without increasing the resources - a potential that may be tapped into by systematic learning from ongoing innovation.

  5. Norris SA, Ho JC, Rashed AA, Vinding V, Skau JK, Biesma R, et al.
    BMC Public Health, 2016 11 17;16(1):1167.
    PMID: 27855663
    BACKGROUND: Malaysia is experiencing a nutrition transition with burgeoning obesity, particularly in women, and a growing prevalence of non-communicable disease. These health burdens have severe implications not only for adult health but also across generations. Pre-conception health promotion could address the intergenerational risk of metabolic disease. This paper describes the development of the "Jom Mama" intervention using Intervention Mapping (IM). The Jom Mama intervention aims to improve the health of young adult couples in Malaysia prior to conception.

    METHODS: IM comprises of five steps prior to the last one, which involves the evaluation of the intervention. We used the five steps to develop the Jom Mama intervention.

    RESULTS: Both the process and evidence is documented providing the rationale to the selection of the key objectives of the intervention: (i) increasing healthy dietary practice; (ii) increasing physical activity levels, (iii) reducing sedentary activity; and (iv) improving social support to offset stressful lifestyles. From the IM process, Jom Mama will be health-system centred approach that uniquely combines both community health promoters and an electronic-health platform to deliver the complex intervention.

    CONCLUSION: IM is an iterative process that systematically gathers "best" evidence, selects appropriate theories of behaviour change, and facilitates formative research so as to develop a complex intervention. Though the IM process is time consuming, complex, and costly, it has enriched the Jom Mama intervention with a number of notable advantages: (i) intervention fashioned on formative work with stakeholders and in the target group; (ii) intervention combines research evidence with theory; (iii) intervention acknowledges multiple dynamics of influence; and (iv) intervention is embedded within health service priorities in Malaysia for greater scale-up possibility.
  6. Colley HE, Said Z, Santocildes-Romero ME, Baker SR, D'Apice K, Hansen J, et al.
    Biomaterials, 2018 09;178:134-146.
    PMID: 29929183 DOI: 10.1016/j.biomaterials.2018.06.009
    Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are chronic inflammatory conditions often characterised by erosive and/or painful oral lesions that have a considerable impact on quality of life. Current treatment often necessitates the use of steroids in the form of mouthwashes, creams or ointments, but these are often ineffective due to inadequate drug contact times with the lesion. Here we evaluate the performance of novel mucoadhesive patches for targeted drug delivery. Electrospun polymeric mucoadhesive patches were produced and characterised for their physical properties and cytotoxicity before evaluation of residence time and acceptability in a human feasibility study. Clobetasol-17-propionate incorporated into the patches was released in a sustained manner in both tissue-engineered oral mucosa and ex vivo porcine mucosa. Clobetasol-17 propionate-loaded patches were further evaluated for residence time and drug release in an in vivo animal model and demonstrated prolonged adhesion and drug release at therapeutic-relevant doses and time points. These data show that electrospun patches are adherent to mucosal tissue without causing tissue damage, and can be successfully loaded with and release clinically active drugs. These patches hold great promise for the treatment of oral conditions such as OLP and RAS, and potentially many other oral lesions.
  7. Skau JK, Nordin AB, Cheah JC, Ali R, Zainal R, Aris T, et al.
    Trials, 2016;17(1):215.
    PMID: 27117703 DOI: 10.1186/s13063-016-1345-x
    Over the past two decades, the population of Malaysia has grown rapidly and the prevalence of diabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia and hypertension. Early-life influences play an important role in the development of non-communicable diseases. Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk of diabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus. This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate the efficacy of a complex behavioural change intervention, combining motivational interviewing provided by a community health promoter and access to a habit formation mobile application, among young Malaysian women and their spouses prior to pregnancy.
  8. Hanafiah AN, Aagaard-Hansen J, Ch Cheah J, Norris SA, Karim ZB, Skau JK, et al.
    J Glob Health, 2022 Aug 17;12:04053.
    PMID: 35972832 DOI: 10.7189/jogh.12.04053
    BACKGROUND: Pre-conception interventions have the potential to lower non-communicable disease risk in prospective parents and reduce transmission of risk factors such as obesity to the next generation. The Jom Mama project in Malaysia investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports the evaluation of the effectiveness of this trial.

    METHODS: Jom Mama was a non-blinded, randomised controlled trial (RCT) conducted in Seremban, Malaysia, over a period of 33 weeks, covering six contact points between trained community health workers and newly married couples before the conception of a first child. Out of 2075 eligible nulliparous women, 549 participated and 305 completed the intervention, with 145 women in the intervention and 160 in the control group. The intervention group received a complex behavioural change intervention, combining behaviour change communication provided by community health promoters and access to a habit formation mobile application, while the control group received the standard care provided by public health clinics in Malaysia. The primary outcome was a change in the woman's waist circumference. Secondary outcomes were anthropometric and metabolic measures, dietary intake (Food Frequency Questionnaire, FFQ), physical activity (International Physical Activity Questionnaire, IPAQ) and mental health (Depression Anxiety Stress Scale, DASS 21). An extensive process evaluation was conducted alongside the trial in order to aid the interpretation of the main findings.

    RESULTS: There were no significant differences of change in the woman's waist circumference between intervention and control groups at the start and end of the intervention. While the weight, waist circumference and Body Mass Index (BMI) of women in both groups increased, there was a significantly lower increase in the intervention vs the control group over the period of the trial among women who are obese (0.1 kg vs 1.7 kg; P = 0.023, in the intervention and control group respectively). In terms of BMI, the obese intervention subgroup showed a slight reduction (0.01) compared to the obese control subgroup whose BMI increased by 0.7 (P = 0.015). There were no changes in the other secondary outcomes.

    CONCLUSIONS: The Jom Mama pre-conception intervention did not lead to a reduction in waist circumference or significant changes in other secondary outcomes over the eight months prior to conception. However, there was a significantly smaller weight gain in the intervention vs the control group, predominantly in women with pre-existing obesity.

  9. Thagaard J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, et al.
    J Pathol, 2023 Aug;260(5):498-513.
    PMID: 37608772 DOI: 10.1002/path.6155
    The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
  10. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  11. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Jun 28;132(26):261902.
    PMID: 38996325 DOI: 10.1103/PhysRevLett.132.261902
    A combination of fifteen top quark mass measurements performed by the ATLAS and CMS experiments at the LHC is presented. The datasets used correspond to an integrated luminosity of up to 5 and 20  fb^{-1} of proton-proton collisions at center-of-mass energies of 7 and 8 TeV, respectively. The combination includes measurements in top quark pair events that exploit both the semileptonic and hadronic decays of the top quark, and a measurement using events enriched in single top quark production via the electroweak t channel. The combination accounts for the correlations between measurements and achieves an improvement in the total uncertainty of 31% relative to the most precise input measurement. The result is m_{t}=172.52±0.14(stat)±0.30(syst)  GeV, with a total uncertainty of 0.33 GeV.
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