Publications by authors named "M J See"

126 Publications

Characterisation of protein-truncating and missense variants in in 15 768 women from Malaysia and Singapore.

J Med Genet 2021 Apr 2. Epub 2021 Apr 2.

Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia

Background: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 () confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.

Methods: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.

Results: PTVs in were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in . However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.

Conclusion: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.
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http://dx.doi.org/10.1136/jmedgenet-2020-107471DOI Listing
April 2021

Psychological distress among cancer survivors during implementation of a nationwide Movement Control Order over the COVID-19 pandemic.

Support Care Cancer 2021 Apr 1. Epub 2021 Apr 1.

Centre for Epidemiology and Evidence-Based Practice, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Objectives: This study aimed to investigate the psychological distress and its associated factors among cancer survivors in Malaysia during the COVID-19 pandemic.

Methods: An anonymous Internet-based study was conducted between 23 April and 26 June 2020. During the study period, the country underwent phase 3 and phase 4 of the Movement Control Order (MCO), Conditional Movement Control Order (CMCO), and Recovery Movement Control Order (RMCO). Psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS), which is a 14-item self-assessment scale for measuring distress (total HADS score; HADS-T) with two subscales, namely, anxiety (HADS-A) and depression (HADS-D). Perceived threat of infection was measured based on the health belief model.

Results: From a total of 631 responses received, the proportion of participants with anxiety and depression symptoms (above threshold score of 8 on HADS-A and HADS-D) was 29.0 and 20.9%, respectively. Psychological distress (HADS-T > 16) was reported in 22.3% of the respondents. A total of 16.5% had combined anxiety and depression symptoms. The highest HADS-A (6.10; 95% CI 5.64-6.56), HADS-D (5.61; 95% CI 5.14-6.08), and HADS-T (11.71; 95% CI 10.84-12.58) scores were reported among respondents during phase 4 of the MCO. Partial least square-based structural equation modelling (PLS-SEM) revealed that self-perceived health status, perceived susceptibility, and severity of COVID-19 have the greatest effect, leading to higher HADS-A, HADS-D, and HADS-T scores.

Conclusion: Heightened psychological distress was evident in cancer survivors particularly during the enforcement of the MCO over COVID-19. Providing support to address cancer survivors' psychological and emotional needs during the COVID-19 pandemic is essential.
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http://dx.doi.org/10.1007/s00520-021-06182-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016501PMC
April 2021

Employing serious game for assessing knowledge of blood transfusion procedure among nurses: A qualitative evaluation and feedback improvement study.

Nurse Educ Today 2021 Mar 20;101:104873. Epub 2021 Mar 20.

Nursing Division (Nursing Quality, Research & Innovation), Singapore General Hospital, Singapore.

Background: Employing serious game for assessing nurses' blood transfusion knowledge and skill competency has gained interest among nurse educators worldwide. However, its acceptance by nurses has not been fully explored.

Aim: To explore the registered nurses' experiences using serious game for nursing skills competency and gather feedback to improve the quality of learning using serious game.

Setting: Acute tertiary hospital in Singapore.

Participants: Registered nurses in inpatient settings.

Methods: This qualitative evaluation and feedback improvement study was conducted in an acute tertiary hospital in Singapore between September 2019 and November 2019. Registered nurses who had completed the blood transfusion knowledge and skills competency via the serious game platform were invited to participate in this study. Individual face-to-face interviews using a semi-structured questionnaire were conducted. All interviews were audio-recorded and transcribed verbatim. Data analysis was performed inductively using the Braun and Clarke's six-step of thematic analysis.

Results: A total of 11 registered nurses were interviewed from a variety of clinical areas including medical and surgical wards, and intensive care units. The mean age of the participants was 28 years old. The majority of participants were females (81.8%), with their years of experience ranging from 1 to 13 years. Each interview took between 20 and 30 min. Three themes were identified: (1) novel learning experience; (2) varying levels of appreciation towards the serious game; and (3) navigating the interface and technical issues.

Conclusion: Employing serious game for nursing skills competency is considered acceptable by the nurses in this sample population. Compared to the traditional modes of competency assessment, the serious game is innovative and stimulates learning. Nevertheless, more rigorous efforts are needed to improve the interface and technical issues to enhance the user learning experience. Future versions of the serious game will need to be more accessible and intuitive for all levels of nursing staffs.
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http://dx.doi.org/10.1016/j.nedt.2021.104873DOI Listing
March 2021

Piper sarmentosum Roxb. Attenuates Beta Amyloid (Aβ)-Induced Neurotoxicity Via the Inhibition of Amyloidogenesis and Tau Hyperphosphorylation in SH-SY5Y Cells.

Curr Alzheimer Res 2021 Mar 24. Epub 2021 Mar 24.

School of Pharmacy, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur. Malaysia.

Background: In Alzheimer's disease, accumulation of beta amyloid (Aβ) triggers amyloidogenesis and hyperphosphorylation of tau protein leading to neuronal cell death. Piper sarmentosum Roxb. (PS) is a traditional medicinal herb used by Malay to treat rheumatism, headache and boost memory. It possesses various biological effects, such as anti-cholinergic, anti-inflammatory, anti-oxidant and anti-depressant-like effects.

Objective: The present study aimed to investigate neuroprotective properties of PS against Aβ-in- duced neurotoxicity and to evaluate its potential mechanism of action.

Methods: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aβ-induced neurotoxic- ity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with Aβ. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aβ and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expres- sions were assessed using qRT-PCR analyses and western blot analyses, respectively.

Results: Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aβ-induced neu- rotoxicity, and decreased levels of extracellular Aβ and phosphorylated tau (pT231). Although ex- tracts of PS inhibited Aβ-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the down regulation of BACE and APP.

Conclusion: These findings suggest that hexane extracts of PS confer neuroprotection against Aβ- induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphoryla- tion. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer's disease.
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http://dx.doi.org/10.2174/1567205018666210324124239DOI Listing
March 2021

Mindful Breathing: Effects of a Five-Minute Practice on Perceived Stress and Mindfulness Among Patients With Cancer.

Clin J Oncol Nurs 2021 Apr;25(2):174-180

University of Malaya.

Background: Cancer can cause undesired side effects that can significantly alter patients' perceived stress and mindfulness. The integration of nonpharmacologic, complementary health interventions, such as mindful breathing, is potentially useful in reducing stress and promoting the well-being of patients during treatment.

Objectives: This study examined the effects of a five-minute mindful breathing practice performed three times per day for three months on perceived stress and mindfulness among patients with cancer.

Methods: This longitudinal, randomized controlled study used a two-group, pre-/post-study design. Patients with distress scores of 4 or higher were randomized into two study arms. Participants in the intervention group were educated on mindfulness and guided on how to perform a five-minute mindful breathing practice. Perceived stress and mindfulness were assessed at baseline, one month postintervention, and three months postintervention.

Findings: Both groups had no significant difference in perceived stress and mindfulness scores at baseline. At three months, the intervention group reported a significant reduction in stress and an increase in mindfulness.

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http://dx.doi.org/10.1188/21.CJON.174-180DOI Listing
April 2021

Outcomes of Asian Women Treated With Grisotti Flap Reconstruction for Centrally Located Breast Cancers: 5-Years Single Institutional Experience.

Ann Plast Surg 2021 Mar 5. Epub 2021 Mar 5.

From the Department of Surgery, University of Malaya Medical Centre, Malaysia.

Introduction: Breast conserving surgeries were previously contraindicated for central breast cancers because of poor cosmetic outcomes of central mastectomy without oncoplastic surgery. Grisotti flap is a breast-conserving surgery incorporating oncoplastic surgery technique for centrally located breast cancers. We present our experience and outcome from Breast Surgery Unit, University Malaya Medical Center.

Materials And Methods: A prospective analysis of 15 patients with central retroareolar breast cancer operated from 2012 to 2018 in University Malaya Medical Center. We assessed postoperative complications, margins, locoregional recurrence, and survival outcome. All patients received postoperative radiotherapy. Patients were followed-up 1 week, 1 month, 3 monthly for 1 year and 6 monthly for 5 years.

Results: Mean age of patients is 62 years. Mean follow-up is 51 months (15-84 months). All tumors were less than 5 cm (1-2.5 cm). Majority of the patients are stage 1 (6 patients/40%) and stage 2 (8 patients/ 53.3%). 2 patients had surgical site infection resolved with antibiotics. One patient had hematoma. None require reoperation. Tumor margins were clear in all patients. No locoregional recurrence. Overall survival is 100%. All are satisfied with their cosmetic outcomes.

Conclusions: Grisotti flap is a volume displacement technique, which provides satisfactory cosmetic outcome for centrally located breast cancer. This evolutionary thinking leads us to changes in existing techniques with the purpose of achieving oncological safety while reaching for better esthetic results. Our 5 years' experience in Asian population showed that this technique is oncologically safe with good cosmetic outcomes and could be used selectively. It provides a good alternative in patients who are otherwise subjected for mastectomy. This relatively simple technique is a worthwhile endeavor and should be offered when feasible.
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http://dx.doi.org/10.1097/SAP.0000000000002631DOI Listing
March 2021

DNA methylation and expression of estrogen receptor alpha in fathead minnows exposed to 17α-ethynylestradiol.

Aquat Toxicol 2021 Apr 23;233:105788. Epub 2021 Feb 23.

US Environmental Protection Agency, Office of Research and Development, Cincinnati, OH, 45268, United States. Electronic address:

The gene expression response thought to underlie the negative apical effects resulting from estrogen exposure have been thoroughly described in fish. Although epigenetics are believed to play a critical role translating environmental exposures into the development of adverse apical effects, they remain poorly characterized in fish species. This study investigated alterations of DNA methylation of estrogen receptor alpha (esr1) in brain and liver tissues from 8 to 10 month old male fathead minnows (Pimephales promelas) after a 2d exposure to either 2.5 ng/L or 10 ng/L 17α-ethynylestradiol (EE2). Changes in the patterns of methylation were evaluated using targeted deep sequencing of bisulfite treated DNA in the 5' region of esr1. Methylation and gene expression were assessed at 2d of exposure and after a 7 and 14d depuration period. After 2d EE2 exposure, males exhibited significant demethylation in the 5' upstream region of esr1 in liver tissue, which was inversely correlated to gene expression. This methylation pattern reflected what was seen in females. No gene body methylation (GBM) was observed for liver of exposed males. Differential methylation was observed for a single upstream CpG site in the liver after the 14d depuration. A less pronounced methylation response was observed in the upstream region in brain tissue, however, several CpGs were necessarily excluded from the analysis. In contrast to the liver, a significant GBM response was observed across the entire gene body, which was sustained until at least 7d post-exposure. No differential expression was observed in the brain, limiting functional interpretation of methylation changes. The identification of EE2-dependent changes in methylation levels strongly suggests the importance of epigenetic mechanisms as a mediator of the organismal response to environmental exposures and the need for further characterization of the epigenome. Further, differential methylation following depuration indicates estrogenic effects persist well after the active exposure, which has implications for the risk posed by repeated exposures..
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http://dx.doi.org/10.1016/j.aquatox.2021.105788DOI Listing
April 2021

Surface Dosimetry of Ultraviolet Germicidal Irradiation Using a Colorimetric Technique.

Ann Work Expo Health 2021 Feb 22. Epub 2021 Feb 22.

National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH, USA.

Ultraviolet germicidal irradiation uses ultraviolet C (UV-C) energy to disinfect surfaces in clinical settings. Verifying that the doses of UV-C energy received by surfaces are adequate for proper disinfection levels can be difficult and expensive. Our study aimed to test commercially available colorimetric labels, sensitive to UV-C energy, and compare their precision with an accepted radiometric technique. The color-changing labels were found to predictably change color in a dose-dependent manner that would allow them to act as a qualitative alternative to radiometry when determining the minimum UV-C energy dosage received at surfaces. If deployed using careful protective techniques to avoid unintentional exposure to sunlight or other light sources, the use of colorimetric labels could provide inexpensive, easy, and accurate verification of effective UV-C dosing in clinical spaces.
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http://dx.doi.org/10.1093/annweh/wxaa147DOI Listing
February 2021

CASPR2 antibody-related movement disorders: case series.

J Neurol 2021 Apr 5;268(4):1533-1535. Epub 2021 Jan 5.

University Hospitals Birmingham NHS Trust, Queen Elizabeth University Hospital Mindelsohn Way Edgbaston, Birmingham, B15 2GW, England.

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http://dx.doi.org/10.1007/s00415-020-10357-wDOI Listing
April 2021

A case series of intestinal obstruction secondary to shiitake mushroom intake during Chinese New Year.

J Surg Case Rep 2020 Oct 14;2020(10):rjaa328. Epub 2020 Oct 14.

Breast Unit, Division of General Surgery, Department of Surgery, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

Shiitake mushroom is a common ingredient in East Asian cuisines. Food processing/preparation can cause the mushroom to be soft and slimy, leading to accidental swallowing. Due to its high insoluble fibre content, it remains the same size and shape in the intestinal tract. We present two cases of small bowel obstruction caused by shiitake mushroom requiring surgical intervention. Preoperative imaging showed dilated small bowel with a suspicious mass in the ileum. However, the exact cause was unclear. For both cases, exploratory laparotomy and enterotomy were then performed and undigested shiitake mushroom was found. Both patients recovered well from the surgery.
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http://dx.doi.org/10.1093/jscr/rjaa328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566373PMC
October 2020

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Authors:
Iris Kramer Maartje J Hooning Nasim Mavaddat Michael Hauptmann Renske Keeman Ewout W Steyerberg Daniele Giardiello Antonis C Antoniou Paul D P Pharoah Sander Canisius Zumuruda Abu-Ful Irene L Andrulis Hoda Anton-Culver Kristan J Aronson Annelie Augustinsson Heiko Becher Matthias W Beckmann Sabine Behrens Javier Benitez Marina Bermisheva Natalia V Bogdanova Stig E Bojesen Manjeet K Bolla Bernardo Bonanni Hiltrud Brauch Michael Bremer Sara Y Brucker Barbara Burwinkel Jose E Castelao Tsun L Chan Jenny Chang-Claude Stephen J Chanock Georgia Chenevix-Trench Ji-Yeob Choi Christine L Clarke J Margriet Collée Fergus J Couch Angela Cox Simon S Cross Kamila Czene Mary B Daly Peter Devilee Thilo Dörk Isabel Dos-Santos-Silva Alison M Dunning Miriam Dwek Diana M Eccles D Gareth Evans Peter A Fasching Henrik Flyger Manuela Gago-Dominguez Montserrat García-Closas José A García-Sáenz Graham G Giles David E Goldgar Anna González-Neira Christopher A Haiman Niclas Håkansson Ute Hamann Mikael Hartman Bernadette A M Heemskerk-Gerritsen Antoinette Hollestelle John L Hopper Ming-Feng Hou Anthony Howell Hidemi Ito Milena Jakimovska Anna Jakubowska Wolfgang Janni Esther M John Audrey Jung Daehee Kang C Marleen Kets Elza Khusnutdinova Yon-Dschun Ko Vessela N Kristensen Allison W Kurian Ava Kwong Diether Lambrechts Loic Le Marchand Jingmei Li Annika Lindblom Jan Lubiński Arto Mannermaa Mehdi Manoochehri Sara Margolin Keitaro Matsuo Dimitrios Mavroudis Alfons Meindl Roger L Milne Anna Marie Mulligan Taru A Muranen Susan L Neuhausen Heli Nevanlinna William G Newman Andrew F Olshan Janet E Olson Håkan Olsson Tjoung-Won Park-Simon Julian Peto Christos Petridis Dijana Plaseska-Karanfilska Nadege Presneau Katri Pylkäs Paolo Radice Gad Rennert Atocha Romero Rebecca Roylance Emmanouil Saloustros Elinor J Sawyer Rita K Schmutzler Lukas Schwentner Christopher Scott Mee-Hoong See Mitul Shah Chen-Yang Shen Xiao-Ou Shu Sabine Siesling Susan Slager Christof Sohn Melissa C Southey John J Spinelli Jennifer Stone William J Tapper Maria Tengström Soo Hwang Teo Mary Beth Terry Rob A E M Tollenaar Ian Tomlinson Melissa A Troester Celine M Vachon Chantal van Ongeval Elke M van Veen Robert Winqvist Alicja Wolk Wei Zheng Argyrios Ziogas Douglas F Easton Per Hall Marjanka K Schmidt

Am J Hum Genet 2020 11 5;107(5):837-848. Epub 2020 Oct 5.

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam 1066 CX, the Netherlands. Electronic address:

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS was quantified using Cox regression analyses. We assessed PRS interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10 percentile and 20.5% at the 90 percentile of PRS. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
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http://dx.doi.org/10.1016/j.ajhg.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675034PMC
November 2020

Oncological safety and postoperative complications in oncoplastic breast surgery among Asian women: A single institutional review.

Breast J 2020 11 29;26(11):2208-2212. Epub 2020 Sep 29.

Breast Surgery Unit, Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Oncoplastic breast surgery (OBS) improves margin clearance and produces good esthetic outcome in breast cancer treatment. This study evaluates the complications and outcome of OBS in a multiracial patient cohort. Data of 421 patients between 2011 and 2018 were analyzed. The majority were Malays (41.8%), followed by Chinese (39.7%) and Indians (16.8%). Low local complications were noted, with no significant differences in disease-free survival (P = .927) and overall survival (P = .719) between low and high OBS levels. Shared decision-making in offering OBS for Asian women has potential to become a practical option in breast cancer treatment.
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http://dx.doi.org/10.1111/tbj.14060DOI Listing
November 2020

Patient literacy and awareness of medicine safety.

Int J Pharm Pract 2020 Dec 15;28(6):552-560. Epub 2020 Sep 15.

Bayer Australia Limited, Pymble, NSW, Australia.

Objective: To assess public understanding of medicine safety, approach to risks and preferences in accessing safety information.

Methods: Qualitative data were obtained from an online survey (n = 1079) covering four major themes around side effects and risks of medicines: willingness to accept side effects of medications, information seeking, sufficiency of information and understanding pharmacovigilance process. Comparisons were made for age, gender and social/financial status.

Key Findings: Most respondents acknowledged medications were associated with side effects. If side effects were experienced, most (73%) would seek advice from their doctor or pharmacist. Four in 10 respondents felt doctors and pharmacists do not provide sufficient information about medications, even though many (47%) relied on their doctor to provide this. Although 51% felt that pharmaceutical companies were already providing enough information to patients, 95% responded that extra effort could still be made. Two-thirds of the respondents felt it was the companies' responsibility to educate doctors and pharmacists so they could pass the information on, even though younger respondents preferred direct communication to patients compared to older respondents (<24 years, 36% versus >65 years, 10%; P < 0.001). Men were more willing to accept risks, while women were more likely to seek information about their medicines. Understanding of the role of pharmaceutical companies and government in maintaining the safety of medicines was generally poor.

Conclusions: There is an ongoing need for consumer education regarding medicine safety. Doctors and pharmacists remain the more trusted source of information. Pharmaceutical companies play an important role in ensuring such information is both accessible and accurate.
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http://dx.doi.org/10.1111/ijpp.12671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692901PMC
December 2020

Risk factors for unplanned hospital readmissions within 30 days of discharge among medical oncology patients: A retrospective medical record review.

Eur J Oncol Nurs 2020 Oct 23;48:101801. Epub 2020 Jul 23.

Nursing Division, Singapore General Hospital, Singapore.

Purpose: This study aimed to identify the risk factors for unplanned hospital readmissions (UHR) within 30 days of discharge among medical oncology patients at a tertiary hospital in Singapore.

Methods: This study is a retrospective, case-control medical record review of patients admitted to a medical oncology unit at a tertiary hospital between 1 June and October 31, 2017. During the study period, there were 1559 adult patients discharged alive from the medical oncology unit. Of this, 359 patients had experienced at least a 30-day UHR (cases). The cases were matched to those without a 30-day UHR (controls) by their primary reason for index admission and discharge date. After matching, 312 medical records (cases: 156; controls: 156) were analysed.

Results: Of the 156 cases with a 30-day UHR, 46.2% (n = 72) were readmitted within the first 10 days of discharge. The top reasons contributing to the UHR were non-neutropenic infection (n = 41) and pain (n = 23). Multivariate analyses identified three independent risk factors that were associated with the 30-day UHR: (1) single marital status, (2) emergency department visit(s) in the past six months, and (3) recent decline in activities of daily living.

Conclusion: The study results can guide risk stratification to identify medical oncology patients at high risk for 30-day UHR. In addition, the results warrant the need to refine the inpatient assessments and discharge planning, as well as ensure the accurate referral to and allocation of community and outpatient resources so as to reduce the risk of UHR.
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http://dx.doi.org/10.1016/j.ejon.2020.101801DOI Listing
October 2020

The YEATS Domain Histone Crotonylation Readers Control Virulence-Related Biology of a Major Human Pathogen.

Cell Rep 2020 04;31(3):107528

Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800 VIC, Australia. Electronic address:

Identification of multiple histone acylations diversifies transcriptional control by metabolism, but their functions are incompletely defined. Here we report evidence of histone crotonylation in the human fungal pathogen Candida albicans. We define the enzymes that regulate crotonylation and show its dynamic control by environmental signals: carbon sources, the short-chain fatty acids butyrate and crotonate, and cell wall stress. Crotonate regulates stress-responsive transcription and rescues C. albicans from cell wall stress, indicating broad impact on cell biology. The YEATS domain crotonylation readers Taf14 and Yaf9 are required for C. albicans virulence, and Taf14 controls gene expression, stress resistance, and invasive growth via its chromatin reader function. Blocking the Taf14 C terminus with a tag reduced virulence, suggesting that inhibiting Taf14 interactions with chromatin regulators impairs function. Our findings shed light on the regulation of histone crotonylation and the functions of the YEATS proteins in eukaryotic pathogen biology and fungal infections.
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http://dx.doi.org/10.1016/j.celrep.2020.107528DOI Listing
April 2020

Breast cancer hormone receptor testing in Asia: is it time to think again on expected positivity rates and methods of scoring?

Pathology 2020 Apr 24;52(3):385-387. Epub 2020 Feb 24.

Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1016/j.pathol.2019.12.006DOI Listing
April 2020

Missed nursing care in patient education: A qualitative study of different levels of nurses' perspectives.

J Nurs Manag 2020 Nov 31;28(8):1960-1967. Epub 2020 Mar 31.

Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.

Aim: To explore the different levels of nurses' perspectives in the delivery of patient education in postoperative care.

Background: Patient education is a frequently reported missed nursing care and can lead to postoperative complications and hospital readmissions.

Methods: Descriptive exploratory qualitative study involving eight focus groups with 35 nurses was conducted in an acute hospital. Interviews were audio-recorded and transcribed verbatim. Data were thematically analysed.

Results: The analysis yielded three themes: 'Role ambiguity' between the levels of nurses concerning their roles in patient education; 'Not a priority nursing care' for patient education due to competing work demands and the missing workplace culture to teach; and 'Informal teaching' carried out conversationally during nursing care activities.

Conclusion: This study augments the need to develop strategies, including informal teaching, to strengthen the delivery of patient education to avert missed nursing care.

Implications For Nursing Management: Nurse managers and educators are instrumental in establishing role clarity between ward nurses and specialty care nurses for patient education, recognizing patient education as the next nurse-sensitive indicator in reflecting quality of care, fostering positive workplace cultures to teach and providing ward nurses with trainings on communication strategies to provide effective informal teaching at bedside.
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http://dx.doi.org/10.1111/jonm.12983DOI Listing
November 2020

The association between methods of biopsy and survival following breast cancer: A hospital registry based cohort study.

Medicine (Baltimore) 2020 Feb;99(6):e19093

Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.

Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteraction < .001). Following multivariable analysis, excision biopsy was consistently associated with lower risk of mortality compared to FNAC in women receiving adjuvant radiotherapy (adjusted hazard ratio: 0.81, 95%CI: 0.66-0.99), but not in those who did not receive adjuvant radiotherapy (adjusted hazard ratio: 0.87, 95%CI: 0.65-1.17). While the risk of mortality was not different between patients undergoing FNAC and CNB when radiotherapy is administered, in the absence of radiotherapy, CNB was associated with higher risk of mortality than FNAC (adjusted hazard ratio: 1.57, 95%CI: 1.16-2.12). Given that our results contradict with findings of previous clinical studies assessing the prognostic impact of method of biopsy in women with breast cancer, further studies are warranted.
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http://dx.doi.org/10.1097/MD.0000000000019093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015568PMC
February 2020

3'-UTRs and the Control of Protein Expression in Space and Time.

Adv Exp Med Biol 2019 ;1203:133-148

Department of Biochemistry and Molecular Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.

The noncoding elements of an mRNA influence multiple aspects of its fate. For example, 3'-UTRs serve as physical and sequence-based information hubs that direct the time, place, and level of translation of the protein encoded in cis, but often also have additional roles in trans. Understanding the information content of 3'-UTRs has been a challenge. Bioinformatic searches for motifs, such as those that encode the polyadenylation signal or microRNA seed regions, are simple enough, but rarely do these inferred positions in genomes correlate well with the actual sites chosen by the relevant nanomachines in living cells. This is almost certainly due to three-dimensional complexity of RNA, the physical states of which are recognized by RNA-binding proteins that serve to read and interpret the information content. Here, we follow the 3'-UTR-mediated posttranscriptional metabolism of mRNA in the germline of the nematode worm Caenorhabditis elegans. While many areas still require the clarification only detailed fundamental research can provide, this model system can serve as a basis of 3'-mediated regulatory control for elaboration in more complex metazoan systems.
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http://dx.doi.org/10.1007/978-3-030-31434-7_5DOI Listing
December 2019

Re-Excision Rates in Breast-Conserving Surgery for Invasive Breast Cancer after Neoadjuvant Chemotherapy with and without the Use of a Radiopaque Tissue Transfer and X-ray System.

Breast Care (Basel) 2019 Oct 14;14(5):302-307. Epub 2018 Nov 14.

Klinik für Gynäkologie und Geburtshilfe, Marienhospital Bottrop, Bottrop, Germany.

Background: Significant re-excision rates in breast-conserving surgery (BCS) after neoadjuvant systemic chemotherapy may result from difficulties in defining the surgical target particularly in cases with excellent treatment response. Devices allowing an exact topographic localisation of the lesion in the resected tissue could reduce re-excision rates by optimising the intraoperative detection of involved margins.

Methods: 80 patients with invasive breast cancer receiving BCS after neoadjuvant chemotherapy were included in this non-randomized case-control study. 40 patients with specimen radiography performed in a standard approach (control group) were compared to 40 patients with use of a radiopaque tissue transfer system (study group).

Results: 19/80 (23.75%) patients required re-excision because of involved margins; among those, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p = 0.023).

Conclusion: Our analysis provides a rationale for the routine use of a radiopaque tissue transfer system for specimen radiography in BCS after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates.
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http://dx.doi.org/10.1159/000493017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883442PMC
October 2019

Gastrointestinal tract metastasis presenting as intussusception in invasive lobular carcinoma of the breast: A case report.

Int J Surg Case Rep 2019 7;64:109-112. Epub 2019 Oct 7.

Department of General Surgery, University Malaya Medical Centre, Lembah Pantai, 59100, Kuala Lumpur, Malaysia. Electronic address:

Introduction: Breast cancer metastasis to the gastrointestinal (GI) tract is rare and occurs more frequently in invasive lobular carcinoma. Patients may be asymptomatic or present with variable vague symptoms that may be mistakenly attributed to side effects of chemotherapy or other benign GI diseases. Treatment follows the principles of systemic disease and includes hormonal therapy, chemotherapy and signal transduction inhibitors, with surgical intervention indicated for complications such as obstruction, perforation and hemorrhage.

Presentation Of Case: We present the case of a female patient with a history of invasive lobular breast carcinoma who had undergone mastectomy and axillary dissection, followed by chemoradiotherapy. Over the next nine years, she developed ovarian and bone metastases for which appropriate treatment was provided. A right iliac fossa mass was discovered during routine clinic review, though she remained asymptomatic. Computed tomography scan showed ileocecal intussusception. Histopathological examination of the right hemicolectomy specimen following emergency surgery confirmed metastatic invasive lobular carcinoma to the GI tract.

Discussion: GI tract metastasis may present 30 years after the primary breast cancer. Up to 20% of patients may be asymptomatic as shown by Montagna et al. When present, symptoms are commonly non-specific and vague. Histological diagnosis is challenging. GI metastasis typically appears as intramural infiltration of the bowel wall by small cells arranged in cords.

Conclusion: It is important to maintain a suspicion for GI tract metastasis in breast cancer patients who present with abdominal mass or GI symptoms, as this aids in prompt institution of accurate and appropriate management.
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http://dx.doi.org/10.1016/j.ijscr.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806597PMC
October 2019

Adherence rate and the factors contribute toward the surgical adherence of breast cancer in Malaysia.

Breast J 2020 03 8;26(3):568-570. Epub 2019 Sep 8.

Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1111/tbj.13617DOI Listing
March 2020

Multigene Biomarkers of Pyrethroid Exposure: Exploratory Experiments.

Environ Toxicol Chem 2019 11 3;38(11):2436-2446. Epub 2019 Oct 3.

Office of Research and Development, National Exposure Research Laboratory, US Environmental Protection Agency, Cincinnati, Ohio, USA.

We describe initial development of microarray-based assays for detecting 4 pyrethroid pesticides (bifenthrin, cypermethrin, esfenvalerate, and permethrin) in water. To facilitate comparison of transcriptional responses with gross apical responses, we estimated concentration-mortality curves for these pyrethroids using flow-through exposures of newly hatched Daphnia magna, Pimephales promelas adults, and 24 h posthatch P. promelas. Median lethal concentration (LC50) estimates were below most reported values, perhaps attributable to the use of flow-through exposures or of measured rather than nominal concentrations. Microarray analysis of whole P. promelas larvae and brains from exposed P. promelas adults showed that assays using either tissue type can detect these pyrethroids at concentrations below LC50 values reported for between 72 and 96% of aquatic species, depending on the pesticide. These estimates are conservative because they correspond to the lowest concentrations tested. This suggests that the simpler and less expensive whole-larval assay provides adequate sensitivity for screening contexts where acute aquatic lethality is observed, but the responsible agent is not known. Gene set analysis (GSA) highlighted several Gene Ontology (GO) terms consistent with known pyrethroid action, but the implications of other GO terms are less clear. Exploration of the sensitivity of results to changes in data processing suggests robustness of the detection assay results, but GSA results were sensitive to methodological variations. Environ Toxicol Chem 2019;38:2436-2446. Published 2019 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America.
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http://dx.doi.org/10.1002/etc.4552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836324PMC
November 2019

Low Breast Conserving Surgery (BCS) rates in public hospitals in Malaysia: The effect of stage and ethnicity.

Breast 2019 Aug 30;46:136-143. Epub 2019 May 30.

Department of General Surgery, University of Malaya Medical Centre, Malaysia.

Introduction: Breast-conserving surgery (BCS) with radiation therapy is the procedure of choice for early-stage breast cancer. Survival and locoregional recurrence is non-inferior to mastectomy, with superior cosmetic and psycho-social outcomes. Differing health systems have demonstrated a wide variation in the rate of BCS. Little is known about the rate of BCS and factors influencing its practice in middle resource countries. This study aims to examine the BCS rates in Malaysia and to identify factors influencing its uptake.

Methodology: This is a multi-centre, cross-sectional study involving the University of Malaya Medical Centre (UMMC), Queen Elizabeth II Hospital (QEH), and Tengku Ampuan Rahimah Hospital (TARH). Patients diagnosed with invasive breast cancer from January 2014 to December 2015 were included, excluding stromal cancers and lymphomas. Univariate and multivariate analyses identified factors influencing BCS.

Results: A total of 1005 patients were diagnosed with breast cancer in the allocated time frame. Excluding incomplete records and those who did not have surgery, 730 patients were analysed. Overall BCS rate was 32.9%. The BCS rate was highest at QEH (54.1%), followed by UMMC (29.5%), and TARH (17.4%). 16.9% had BCS after neoadjuvant therapy. Factors influencing BCS uptake included age, ethnic group, breast-surgeon led services, AJCC Stage, tumour size, HER-2 expression, and tumour grade.

Conclusions: The rate of BCS in Malaysia is low. A wide variation of rate exists among the studied hospitals. Younger age, earlier AJCC stage, and the presence of a Breast sub-specialist surgeon, would make it more likely that the patient has her breast conserved.
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http://dx.doi.org/10.1016/j.breast.2019.05.016DOI Listing
August 2019

Significant factors influencing inadvertent hypothermia in pediatric anesthesia.

J Clin Monit Comput 2019 Dec 26;33(6):1105-1112. Epub 2019 Mar 26.

Department of Anesthesia, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Thermal imbalances are very common during surgery. Hypothermia exposes the patient to post-operative shivering, cardiac dysfunction, coagulopathy, bleeding, wound infection, delayed anesthesia recovery, prolonged hospital stay and increased hospitalization cost. There are many factors contributing to intraoperative hypothermia. This is a prospective cohort study conducted through observation and measurement of pediatric surgical patients' temperature. Convenience sampling methods were used in this study. Initial skin temperature and core temperature at 10 min, 30 min,1 h, 2 h, 3 h, 4 h, 5 h, 6 h and at the end of surgery were recorded. Body temperature was monitored from time of transfer to the operating table until recovery and discharge to the respective pediatric ward. The overall incidence of intraoperative hypothermia was still very high at about 46.6% even though active and passive temperature management were carried out during surgery. Patient's age, body weight, duration of surgery, type of surgery, intraoperative blood loss, type of anesthesia and operating room temperature were factors that contributed to intraoperative hypothermia. Hypothermia is common in surgery, especially in major and long duration surgery. Intraoperative hypothermia can be life threatening if it is not handled carefully. Various methods are used before, during and after surgery to maintain a patient's body temperature within the normothermia range. The use of an active warming device like the Bair Hugger® air-forced warming system seems to be a good method for reducing the risk of intraoperative hypothermia and effectively maintaining body temperature for all major and minor surgeries.
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http://dx.doi.org/10.1007/s10877-019-00259-2DOI Listing
December 2019

Evaluation of Ge-doped silica fibre TLDs for in vivo dosimetry during intraoperative radiotherapy.

Phys Med Biol 2019 04 12;64(8):08NT04. Epub 2019 Apr 12.

Department of Physics, University of Malaya, Kuala Lumpur, Malaysia. Author to whom any correspondence should be addressed.

Ge-doped silica fibre (GDSF) thermoluminescence dosimeters (TLD) are non-hygroscopic spatially high-resolution radiation sensors with demonstrated potential for radiotherapy dosimetry applications. The INTRABEAM system with spherical applicators, one of a number of recent electronic brachytherapy sources designed for intraoperative radiotherapy (IORT), presents a representative challenging dosimetry situation, with a low keV photon beam and a desired rapid dose-rate fall-off close-up to the applicator surface. In this study, using the INTRABEAM system, investigations were made into the potential application of GDSF TLDs for in vivo IORT dosimetry. The GDSFs were calibrated over the respective dose- and depth-range 1 to 20 Gy and 3 to 45 mm from the x-ray probe. The effect of different sizes of spherical applicator on TL response of the fibres was also investigated. The results show the GDSF TLDs to be applicable for IORT dose assessment, with the important incorporated correction for beam quality effects using different spherical applicator sizes. The total uncertainty in use of this type of GDSF for dosimetry has been found to range between 9.5% to 12.4%. Subsequent in vivo measurement of skin dose for three breast patients undergoing IORT were performed, the measured doses being below the tolerance level for acute radiation toxicity.
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http://dx.doi.org/10.1088/1361-6560/ab0d4eDOI Listing
April 2019

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells.

Curr Alzheimer Res 2019 ;16(3):251-260

School of Pharmacy, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments.

Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators.

Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay.

Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators.

Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).
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http://dx.doi.org/10.2174/1567205016666190228124630DOI Listing
June 2020

The Ideal Nipple Reconstruction Shield.

Plast Reconstr Surg 2019 03;143(3):698-699

From the Department of Plastic and Reconstructive Surgery, Guys & St Thomas' Hospital.

Reconstruction of the nipple-areola complex is the culmination of a long road for patients who have suffered breast cancer. The postoperative dressing of the reconstructive nipple must protect it from mechanical forces, trauma, and infection. A broad array of dressings has been used for the reconstructed nipple. The authors propose the use of a readily available adhesive eye protector as a simple and cost-effective dressing for the reconstructed nipple-areola complex.
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http://dx.doi.org/10.1097/PRS.0000000000005318DOI Listing
March 2019

Breast-conserving surgery mastectomy in young women with breast cancer in Asian settings.

BJS Open 2019 02 18;3(1):48-55. Epub 2018 Oct 18.

Department of Social and Preventive Medicine, Faculty of Medicine University of Malaya Kuala Lumpur Malaysia.

Background: Mastectomy rates among women with early breast cancer in Asia have traditionally been high. This study assessed trends in the surgical management of young women with early-stage breast cancer in Asian settings. Survival in women treated with breast-conserving surgery (BCS; lumpectomy with adjuvant radiotherapy) and those undergoing mastectomy was compared.

Methods: Young women (aged less than 50 years) newly diagnosed with stage I or II (T1-2 N0-1 M0) breast cancer in four hospitals in Malaysia, Singapore and Hong Kong in 1990-2012 were included. Overall survival (OS) was compared for patients treated by BCS and those who had a mastectomy. Propensity score analysis was used to account for differences in demographic, tumour and treatment characteristics between the groups.

Results: Some 63·5 per cent of 3536 women underwent mastectomy. Over a 15-year period, only a modest increase in rates of BCS was observed. Although BCS was significantly associated with favourable prognostic features, OS was not significantly different for BCS and mastectomy; the 5-year OS rate was 94·9 (95 per cent c.i. 93·5 to 96·3) and 92·9 (91·7 to 94·1) per cent respectively. Inferences remained unchanged following propensity score analysis (hazard ratio for BCS mastectomy: 0·81, 95 per cent c.i. 0·64 to 1·03).

Conclusion: The prevalence of young women with breast cancer treated by mastectomy remains high in Asian countries. Patients treated with BCS appear to survive as well as those undergoing mastectomy.
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http://dx.doi.org/10.1002/bjs5.50111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354186PMC
February 2019

Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high-income countries.

Psychooncology 2019 01 30;28(1):147-153. Epub 2018 Oct 30.

Department of Surgery, Subang Jaya Medical Centre, Subang Jaya, Malaysia.

Objectives: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women.

Methods: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients.

Results: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes.

Conclusion: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes.
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http://dx.doi.org/10.1002/pon.4924DOI Listing
January 2019