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Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial

Zahari M, Lee DS, Darlow BA

J Clin Monit Comput, 2016 Oct;30(5):669-78.
PMID: 26282827 DOI: 10.1007/s10877-015-9752-1

The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10 s up to 36 weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least two weeks of stored data. Oxygen saturation distribution patterns corresponding with a +3 % or -3 % offset in the 85-95 % range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87 % and a peak at 96 % from the lower saturation target oximeters, and at 93-95 and 84 % respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90 %. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies.
Fulltext Diffuse Pulmonary Uptake of Tc-99m Methylene Diphosphonate in a Patient with Non-tuberculosis Mycobacterial Infection

Kwon HW, Chung JK, Ab-Aziz A, Lee DS

Nucl Med Mol Imaging, 2010 Jun;44(2):146-9.
PMID: 25013527 DOI: 10.1007/s13139-010-0020-5

Extra-osseous uptake of bone-seeking radiopharmaceuticals has been reported at various sites and it is known to be induced by various causes. Diffuse pulmonary infection, such as tuberculosis, can be a cause of lung uptake of bone-scan agent. Here we report on a patient with non-tuberculosis mycobacterial infection (NTM) who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan. After medical treatment for NTM, the patient's lung lesions improved. Extraskeletal lung Tc-99m MDP uptake on bone scan may suggest lung parenchymal damage associated with disease activity.
An integrated review of the correlation between critical thinking ability and clinical decision-making in nursing

Lee DS, Abdullah KL, Subramanian P, Bachmann RT, Ong SL

J Clin Nurs, 2017 Dec;26(23-24):4065-4079.
PMID: 28557238 DOI: 10.1111/jocn.13901

AIMS AND OBJECTIVES: To explore whether there is a correlation between critical thinking ability and clinical decision-making among nurses.
BACKGROUND: Critical thinking is currently considered as an essential component of nurses' professional judgement and clinical decision-making. If confirmed, nursing curricula may be revised emphasising on critical thinking with the expectation to improve clinical decision-making and thus better health care.
DESIGN: Integrated literature review.
METHODS: The integrative review was carried out after a comprehensive literature search using electronic databases Ovid, EBESCO MEDLINE, EBESCO CINAHL, PROQuest and Internet search engine Google Scholar. Two hundred and 22 articles from January 1980 to end of 2015 were retrieved. All studies evaluating the relationship between critical thinking and clinical decision-making, published in English language with nurses or nursing students as the study population, were included. No qualitative studies were found investigating the relationship between critical thinking and clinical decision-making, while 10 quantitative studies met the inclusion criteria and were further evaluated using the Quality Assessment and Validity Tool. As a result, one study was excluded due to a low-quality score, with the remaining nine accepted for this review.
RESULTS: Four of nine studies established a positive relationship between critical thinking and clinical decision-making. Another five studies did not demonstrate a significant correlation. The lack of refinement in studies' design and instrumentation were arguably the main reasons for the inconsistent results.
CONCLUSIONS: Research studies yielded contradictory results as regard to the relationship between critical thinking and clinical decision-making; therefore, the evidence is not convincing. Future quantitative studies should have representative sample size, use critical thinking measurement tools related to the healthcare sector and evaluate the predisposition of test takers towards their willingness and ability to think. There is also a need for qualitative studies to provide a fresh approach in exploring the relationship between these variables uncovering currently unknown contributing factors.
RELEVANCE TO CLINICAL PRACTICE: This review confirmed that evidence to support the existence of relationships between critical thinking and clinical decision-making is still unsubstantiated. Therefore, it serves as a call for nurse leaders and nursing academics to produce quality studies in order to firmly support or reject the hypothesis that there is a statistically significant correlation between critical thinking and clinical decision-making.
Real world long-term outcomes among adults undergoing transcatheter patent foramen closure with amplatzer PFO occluder

Abrahamyan L, Barker M, Dharma C, Lee DS, Austin PC, Asghar A, et al.

Int J Cardiol, 2023 Jan 15;371:109-115.
PMID: 36165815 DOI: 10.1016/j.ijcard.2022.09.033

BACKGROUND: Patent foramen ovale (PFO) is a congenital heart defect associated with an increased risk of cryptogenic stroke. We aimed to evaluate real-world outcomes of adult patients undergoing transcatheter PFO closure with the Amplatzer PFO Occluder.
METHODS: In this single centre, retrospective cohort study, we linked a detailed clinical registry with provincial administrative databases to obtain short and long-term outcomes. Validated algorithms were used to established baseline comorbidities and adverse outcomes.
RESULTS: Between 1999 and 2017, 479 patients had PFO closure with an Amplatzer PFO Occluder. The average age of the patients was 47.3 years (standard deviation (SD) = 12.4), and 54.7% were males. The procedural success was 100%, and 96% of patients were discharged on the same day. Any in-hospital complication was observed in 2.5% (n = 12) of patients. At 30 days post-discharge, 18% of patients had an ED visit and 5% a hospitalization. Over a mean follow-up of 9.1 (SD = 3.8) years, 4% experienced TIA, 1.5% stroke, and 7.6% atrial fibrillation. The composite outcome of stroke/TIA/death was observed in 10.9% of patients (1.22 events per 100 person-years). Patients >60 years old experienced higher rates of adverse events than younger patients.
CONCLUSIONS: In this large real-world cohort of patients with cryptogenic stroke, we observed excellent safety and effectiveness outcomes for PFO closure conducted with Amplatzer PFO Occluder, similar to randomized controlled trials or other long-term cohort studies. New onset atrial fibrillation was one of the most commonly adverse events. Future studies should investigate early post-discharge management of patients to prevent readmissions.
Communication about positive BRCA1 and BRCA2 genetic test results and uptake of testing in relatives in a diverse Asian setting

Lee DS, Meiser B, Mariapun S, Hassan T, Yip CH, Mohd Taib NA, et al.

J Genet Couns, 2021 Jun;30(3):720-729.
PMID: 33245177 DOI: 10.1002/jgc4.1360

The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty-seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi-structured interview guide. Fifty-six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first- and second-degree relatives were informed by the proband about the testing result and that 11.5% of eligible first- and second-degree relatives had genetic testing. First-degree relatives were more likely to have been informed and tested compared to second-degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second-degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes.
Fulltext BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history

Toh GT, Kang P, Lee SS, Lee DS, Lee SY, Selamat S, et al.

PLoS One, 2008;3(4):e2024.
PMID: 18431501 DOI: 10.1371/journal.pone.0002024

BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.
METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (
Fulltext Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients

Lee DS, Yoon SY, Looi LM, Kang P, Kang IN, Sivanandan K, et al.

Breast Cancer Res, 2012;14(2):R66.
PMID: 22507745

Germline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, in Asia and in many low resource settings, it is challenging to obtain accurate family history and we, therefore, sought to determine whether the presence of early-onset breast cancer is an appropriate selection criteria for germline TP53 testing.
Fulltext Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, et al.

Breast Cancer Res, 2008;10(4):R59.
PMID: 18627636 DOI: 10.1186/bcr2118

The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.
Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort

Padmanabhan H, Mariapun S, Lee SY, Hassan NT, Lee DS, Meiser B, et al.

J Genet Couns, 2023 Feb;32(1):43-56.
PMID: 35913122 DOI: 10.1002/jgc4.1619

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies.
Fulltext A case-control study of breast cancer risk factors in 7,663 women in Malaysia

Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al.

PLoS One, 2018;13(9):e0203469.
PMID: 30216346 DOI: 10.1371/journal.pone.0203469

BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women.
METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity.
RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy.
CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.
Fulltext Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.

J Med Genet, 2018 02;55(2):97-103.
PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947

BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.
METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.
RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.
CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.
Fulltext Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data

Cannarella R, Shah R, Hamoda TAA, Boitrelle F, Saleh R, Gul M, et al.

World J Mens Health, 2024 Jan;42(1):92-132.
PMID: 37382284 DOI: 10.5534/wjmh.230034

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.
MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).
RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864.
CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.
Fulltext Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Ghoussaini M, Edwards SL, Michailidou K, Nord S, Cowper-Sal Lari R, Desai K, et al.

Nat Commun, 2014 Sep 23;4:4999.
PMID: 25248036 DOI: 10.1038/ncomms5999

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.

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