Displaying publications 101 - 120 of 225 in total

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  1. Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.
    Mucosal Immunol, 2016 Jul;9(4):859-72.
    PMID: 26555706 DOI: 10.1038/mi.2015.111
    Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
  2. Bhoo-Pathy N, Yip CH, Hartman M, Uiterwaal CS, Devi BC, Peeters PH, et al.
    Eur J Cancer, 2013 Feb;49(3):703-9.
    PMID: 23040889 DOI: 10.1016/j.ejca.2012.09.014
    The incidence and mortality of breast cancer continues to rise rapidly in Asian countries. However, most of our current knowledge on breast cancer has been generated in Western populations. As the socio-economic profile, life style and culture of Asian and Western women are substantially different, and genetic backgrounds vary to some extent, we need to answer the question on whether to 'adopt' or 'adapt' Western knowledge before applying it in the Asian setting. It is generally accepted that breast cancer risk factors, which have mainly been studied in Western populations are similar worldwide. However, the presence of gene-environment or gene-gene interactions may alter their importance as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, are increasingly shown to be 'setting specific' and must therefore be validated in Asian women before implementing them in clinical care in Asia. Interventional research findings from Caucasian patients may not be applicable in patients in Asia due to differences in tumour biology/profiles, metabolism of drugs and also health beliefs which can influence treatment acceptance and adherence. While breast cancer research in Asia is warranted in all domains of medical research, it is felt that for Asian breast cancer patients, needs are highest for diagnostic and prognostic studies. International clinical trials meanwhile need to include breast cancer patients from various Asian settings to provide an insight into the effectiveness of new treatment modalities in this part of the world.
  3. Shakya R, Tarulli GA, Sheng L, Lokman NA, Ricciardelli C, Pishas KI, et al.
    Oncogene, 2017 08;36(31):4469-4480.
    PMID: 28368395 DOI: 10.1038/onc.2017.66
    Missense mutations in the TP53 tumor-suppressor gene inactivate its antitumorigenic properties and endow the incipient cells with newly acquired oncogenic properties that drive invasion and metastasis. Although the oncogenic effect of mutant p53 transcriptome has been widely acknowledged, the global influence of mutant p53 on cancer cell proteome remains to be fully elucidated. Here, we show that mutant p53 drives the release of invasive extracellular factors (the 'secretome') that facilitates the invasion of lung cancer cell lines. Proteomic characterization of the secretome from mutant p53-inducible H1299 human non-small cell lung cancer cell line discovered that the mutant p53 drives its oncogenic pathways through modulating the gene expression of numerous targets that are subsequently secreted from the cells. Of these genes, alpha-1 antitrypsin (A1AT) was identified as a critical effector of mutant p53 that drives invasion in vitro and in vivo, together with induction of epithelial-mesenchymal transition markers expression. Mutant p53 upregulated A1AT transcriptionally through the involvement with its family member p63. Conditioned medium containing secreted A1AT enhanced cell invasion, while an A1AT-blocking antibody attenuated the mutant p53-driven migration and invasion. Importantly, high A1AT expression correlated with increased tumor stage, elevated p53 staining and shorter overall survival in lung adenocarcinoma patients. Collectively, these findings suggest that A1AT is an indispensable target of mutant p53 with prognostic and therapeutic potential in mutant p53-expressing tumors.
  4. Lim WY, Turner RM, Morton RL, Jenkins MC, Irwig L, Webster AC, et al.
    BMC Health Serv Res, 2018 06 20;18(1):477.
    PMID: 29925350 DOI: 10.1186/s12913-018-3291-7
    BACKGROUND: Patients may decide to undertake shared care with a general practitioner (GP) during follow-up after treatment for localised melanoma. Routine imaging tests for surveillance may be commonly used despite no evidence of clinical utility. This study describes the frequency of shared care and routine tests during follow-up after treatment for localised melanoma.

    METHODS: We randomly sampled 351 people with localised melanoma [American Joint Cancer Committee (AJCC) substages 0 - II] who had not had recurrent or new primary melanoma diagnosed from a total of 902 people diagnosed and treated for localised melanoma at a specialist centre in 2014. We interviewed participants by telephone about their experience of follow-up in the past year, and documented the proportion of patients who were undertaking shared care follow-up with a GP. We also recorded the frequency and type of investigations during follow-up. We calculated weighted estimates that are representative of the full inception cohort.

    RESULTS: Of the 351 people who were invited to participate, 230 (66%) people consented to the telephone interview. The majority undertook shared care follow-up with a GP (61%). People who choose to have shared care follow-up with a GP are more likely to be male (p = 0.006), have lower AJCC stage (p for trend = 0.02), reside in more remote areas (p for trendp 

  5. Chew MH, Arguin PM, Shay DK, Goh KT, Rollin PE, Shieh WJ, et al.
    J Infect Dis, 2000 May;181(5):1760-3.
    PMID: 10823780
    During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.
  6. Subramaniam S, Kong YC, Zaharah H, Uiterwaal CSPM, Richard A, Taib NA, et al.
    Ecancermedicalscience, 2021;15:1293.
    PMID: 34824616 DOI: 10.3332/ecancer.2021.1293
    Purpose: To measure the baseline prevalence of cardiovascular disease (CVD), its modifiable and non-modifiable risk factors in breast cancer patients, and determine their association with adjuvant treatment decision-making.

    Method: From 2016 to 2017, 2,127 women newly-diagnosed with breast cancer were prospectively recruited. Participants' cardiovascular biomarkers were measured prior to adjuvant treatment decision-making. Clinical data and medical histories were obtained from hospital records. Adjuvant treatment decisions were collated 6-8 months after recruitment. A priori risk of cardiotoxicity was predicted using the Cardiotoxicity Risk Score.

    Results: Mean age was 54 years. Eighty-five patients had pre-existing cardiac diseases and 30 had prior stroke. Baseline prevalence of hypertension was 47.8%. Close to 20% had diabetes mellitus, or were obese. Dyslipidaemia was present in 65.3%. The proportion of women presenting with ≥2 modifiable CVD risk factors at initial cancer diagnosis was substantial, irrespective of age. Significant ethnic variations were observed. Multivariable analyses showed that pre-existing CVD was consistently associated with lower administration of adjuvant breast cancer therapies (odds ratio for chemotherapy: 0.32, 95% confidence interval: 0.17-0.58). However, presence of multiple risk factors of CVD did not appear to influence adjuvant treatment decision-making. In this study, 63.6% of patients were predicted to have high risks of developing cardiotoxicities attributed to a high baseline burden of CVD risk factors and anthracycline administration.

    Conclusion: While recent guidelines recommend routine assessment of cardiovascular comorbidities in cancer patients prior to initiation of anticancer therapies, this study highlights the prevailing gap in knowledge on how such data may be used to optimise cancer treatment decision-making.

  7. Lim WY, Morton RL, Turner RM, Jenkins MC, Guitera P, Irwig L, et al.
    JAMA Dermatol, 2018 04 01;154(4):420-427.
    PMID: 29490373 DOI: 10.1001/jamadermatol.2018.0021
    Importance: The standard model of follow-up posttreatment of localized melanoma relies on clinician detection of recurrent or new melanoma, through routinely scheduled clinics (clinician-led surveillance). An alternative model is to increase reliance on patient detection of melanoma, with fewer scheduled visits and increased support for patients' skin self-examination (SSE) (eg, using smartphone apps to instruct, prompt and record SSE, and facilitate teledermatology; patient-led surveillance).

    Objective: To determine the proportion of adults treated for localized melanoma who prefer the standard scheduled visit frequency (as per Australian guideline recommendations) or fewer scheduled visits (adapted from the Melanoma Follow-up [MELFO] study of reduced follow-up).

    Design, Setting, and Participants: This survey study used a telephone interview for surveillance following excision of localized melanoma at an Australian specialist center. We invited a random sample of 400 patients who had completed treatment for localized melanoma in 2014 to participate. They were asked about their preferences for scheduled follow-up, and experience of follow-up in the past 12 months. Those with a recurrent or new primary melanoma diagnosed by the time of interview (0.8-1.7 years since first diagnosis) were asked about how it was first detected and treated. SSE practices were also assessed.

    Main Outcomes and Measures: Proportion preferring standard vs fewer scheduled clinic visits, median delay between detection and treatment of recurrent or new primary melanoma, and SSE practices.

    Results: Of the 262 people who agreed to be interviewed, the mean (SD) age was 64.3 (14.3) years, and 93 (36%) were women. Among the 230 people who did not have a recurrent or new primary melanoma, 149 vs 81 preferred the standard vs fewer scheduled clinic visits option (70% vs 30% after adjusting for sampling frame). Factors independently associated with preferring fewer visits were a higher disease stage, melanoma on a limb, living with others, not having private health insurance, and seeing a specialist for another chronic condition. The median delay between first detection and treatment of recurrent or new primary melanoma was 7 and 3 weeks, respectively. Only 8% missed a scheduled visit, while 40% did not perform SSE or did so at greater than 3-month intervals.

    Conclusions and Relevance: Some patients with melanoma may prefer fewer scheduled visits, if they are supported to do SSE and there is rapid clinical review of anything causing concern (patient-led surveillance).

  8. Padma Priya S, Higuchi A, Abu Fanas S, Pooi Ling M, Kumari Neela V, Sunil PM, et al.
    Lab Invest, 2015 Dec;95(12):1344-52.
    PMID: 26367485 DOI: 10.1038/labinvest.2015.108
    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed.
  9. Song CV, Yip CH, Mohd Taib NA, See MH, Teoh LY, Monninkhof EM, et al.
    JCO Glob Oncol, 2022 Mar;8:e2100314.
    PMID: 35245099 DOI: 10.1200/GO.21.00314
    PURPOSE: Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined.

    METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.

    RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.

    CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.

  10. Priya SP, Sunil PM, Varma S, Brigi C, Isnadi MFAR, Jayalal JA, et al.
    Virusdisease, 2022 Dec;33(4):429-444.
    PMID: 36311173 DOI: 10.1007/s13337-022-00793-9
    BACKGROUND: Severe acute respiratory syndrome Coronavirus-2 invades the cells via ACE2 receptor and damages multiple organs of the human body. Understanding the pathological manifestation is mandatory to endure the rising post-infection sequel reported in patients with or without comorbidities.

    MATERIALS AND METHODS: Our descriptive review emphasises the direct, indirect and post-infection damages due to COVID-19. We have performed an electronic database search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with selective inclusion and exclusion criteria.

    RESULTS: The included studies substantiated the extensive damages in the multiple organs due to direct and indirect consequences of COVID-19. After an apparent recovery, the prolonged presentation of the symptoms manifests as post-COVID that can be related with persisting viral antigens and dysregulated immune response.

    CONCLUSION: A few of the symptoms of respiratory, cardiovascular, and neuropsychiatric systems that persist or reappear as post-COVID manifestations. Vaccination and preventive programs will effectively reduce the prevalence but, the post-COVID, a multisystem manifestation, will be a significant tribulation to the medical profession. However, the issue can be managed by implementing public health programs, rehabilitation services, and telemedicine virtual supports to raise awareness and reduce panic.

  11. Vaithilingam RD, Safii SH, Baharuddin NA, Karen-Ng LP, Saub R, Ariffin F, et al.
    Oral Dis, 2015 Jan;21(1):e62-9.
    PMID: 24930489 DOI: 10.1111/odi.12267
    Periodontal bio-repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad-based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.
  12. Colella JP, Agwanda BR, Anwarali Khan FA, Bates J, Carrión Bonilla CA, de la Sancha NU, et al.
    Science, 2020 11 13;370(6518):773-774.
    PMID: 33184198 DOI: 10.1126/science.abe4813
  13. Ahmed HMA, Che Ab Aziz ZA, Azami NH, Farook MS, Khan AA, Mohd Noor NS, et al.
    Int Endod J, 2020 Jun;53(6):871-879.
    PMID: 32003029 DOI: 10.1111/iej.13271
    AIM: To evaluate and compare the feedback of final year undergraduate dental students in eight Malaysian dental schools on the application of a new system for classifying root canal morphology in teaching and clinical practice.

    METHODS: One PowerPoint presentation describing two classification systems for root canal morphology (Oral Surgery Oral Medicine Oral Pathology, 1974 38, 456 and its supplemental configurations, International Endodontic Journal 2017, 50, 761) was delivered to final year undergraduate dental students in eight dental schools in Malaysia by two presenters (each presented to four schools). To examine students' feedback on the utility of each system, printed questionnaires consisting of six questions (five multiple choice questions and one open-ended question) were distributed and collected after the lecture. The questionnaire was designed to compare the classification systems in terms of accuracy, practicability, understanding of root canal morphology and recommendation for use in pre-clinical and clinical courses. The exact test was used for statistical analysis, with the level of significance set at 0.05 (P = 0.05).

    RESULTS: A total of 382 (out of 447) students participated giving a response rate of 86%. More than 90% of students reported that the new system was more accurate and more practical compared with the Vertucci system (P P P P > 0.05). The students' responses for all questions were almost similar for both presenters (P > 0.05).

    CONCLUSIONS: The new system of International Endodontic Journal 2017, 50, 761 for classifying root and canal morphology was favoured by final year undergraduate dental students in Malaysia. The new system has the potential to be included in the undergraduate endodontic curriculum for teaching courses related to root and canal morphology.

  14. Thompson CW, Phelps KL, Allard MW, Cook JA, Dunnum JL, Ferguson AW, et al.
    mBio, 2021 Jan 12;12(1).
    PMID: 33436435 DOI: 10.1128/mBio.02698-20
    Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.
  15. A MH, C A R N, S M C, S R, P M, R H WS, et al.
    PLoS One, 2023;18(7):e0288325.
    PMID: 37459344 DOI: 10.1371/journal.pone.0288325
    INTRODUCTION: The current and simpler healthy eating concept 'Malaysian Healthy Plate', was introduced in 2016. This study aims to determine the prevalence of ever-never heard, understanding, and practice of this concept and also the associated factors to never-heard of Malaysian Health Plate after three years of the implementation.

    METHODOLOGY: This study utilized the data from the National Health and Morbidity Survey (NHMS) 2019, a cross-sectional survey that applied two-stage stratified cluster sampling. Questionnaires pertained to ever heard, knowledge, and practised of Malaysian Healthy Plate were asked along with another questionnaire. Complex sample analysis was applied to fit with the study design.

    RESULTS: Estimated 16.9 million (79.6%) adults in Malaysia were never heard of the Malaysian Healthy Plate Concept in 2019. Never heard of this concept was significantly associated with sex (men, aOR 0.265), ethnicity (other ethnicities, aOR 1.79), an education level (no education, aOR 9.59; primary, aOR 3.50; secondary, aOR 1.70), occupation (private, aOR 2.16; self-employed, aOR 2.31; retirees, aOR 1.69; student, aOR 2.31; unpaid workers, aOA 2.35; not working, aOR 2.86), non-diabetes aOR 1.43, and low fruit and vegetable intake person aOR 1.86. Meanwhile, another 20.4% or an estimated 4.3 million adults who were ever heard of Malaysian Healthy Plate. Among those who are ever heard, 80.8% (3.5 million) correctly interpreted or understood the concept and among those who ever heard and understood the concept, only 70.5% (2.5 million) have been practising it daily or occasionally.

    CONCLUSIONS: Four-fifth of adults never heard of the 'Malaysian Healthy Plate' and among those who ever heard, the understanding and practising of the concept were probably unsatisfactory. Multisectoral collaboration is an urge to fasten the promotion to spark awareness and educate the public to practice the concept to promote healthy eating and a healthier nation.

  16. MacKenzie AR, Langford B, Pugh TA, Robinson N, Misztal PK, Heard DE, et al.
    Philos Trans R Soc Lond B Biol Sci, 2011 Nov 27;366(1582):3177-95.
    PMID: 22006961 DOI: 10.1098/rstb.2011.0053
    We report measurements of atmospheric composition over a tropical rainforest and over a nearby oil palm plantation in Sabah, Borneo. The primary vegetation in each of the two landscapes emits very different amounts and kinds of volatile organic compounds (VOCs), resulting in distinctive VOC fingerprints in the atmospheric boundary layer for both landscapes. VOCs over the Borneo rainforest are dominated by isoprene and its oxidation products, with a significant additional contribution from monoterpenes. Rather than consuming the main atmospheric oxidant, OH, these high concentrations of VOCs appear to maintain OH, as has been observed previously over Amazonia. The boundary-layer characteristics and mixing ratios of VOCs observed over the Borneo rainforest are different to those measured previously over Amazonia. Compared with the Bornean rainforest, air over the oil palm plantation contains much more isoprene, monoterpenes are relatively less important, and the flower scent, estragole, is prominent. Concentrations of nitrogen oxides are greater above the agro-industrial oil palm landscape than over the rainforest, and this leads to changes in some secondary pollutant mixing ratios (but not, currently, differences in ozone). Secondary organic aerosol over both landscapes shows a significant contribution from isoprene. Primary biological aerosol dominates the super-micrometre aerosol over the rainforest and is likely to be sensitive to land-use change, since the fungal source of the bioaerosol is closely linked to above-ground biodiversity.
  17. Simoneau G, Levis B, Cuijpers P, Ioannidis JPA, Patten SB, Shrier I, et al.
    Biom J, 2017 Nov;59(6):1317-1338.
    PMID: 28692782 DOI: 10.1002/bimj.201600184
    Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings.
  18. Lau EPM, Ing M, Vekaria S, Tan AL, Charlesworth C, Fysh E, et al.
    Trials, 2024 Apr 10;25(1):249.
    PMID: 38594766 DOI: 10.1186/s13063-024-08065-1
    BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC.

    METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants.

    DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections.

    ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences.

    TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

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