Displaying publications 21 - 40 of 49 in total

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  1. Waseem R, Chan MTV, Wang CY, Seet E, Tam S, Loo SY, et al.
    J Clin Sleep Med, 2021 03 01;17(3):521-532.
    PMID: 33112227 DOI: 10.5664/jcsm.8940
    STUDY OBJECTIVES: The STOP-Bang questionnaire is a concise and easy screening tool for obstructive sleep apnea (OSA). Using modified body mass index (BMI), we assessed the diagnostic performance of the STOP-Bang questionnaire in predicting OSA in ethnically different groups of patients undergoing surgery.

    METHODS: This was a multicenter prospective cohort study involving patients with cardiovascular risk factors who were undergoing major noncardiac surgery. Patients underwent home sleep apnea testing. All patients completed the STOP-Bang questionnaire. The predictive parameters of STOP-Bang scores were calculated against the apnea-hypopnea index.

    RESULTS: From 4 ethnic groups 1,205 patients (666 Chinese, 161 Indian, 195 Malay, and 183 Caucasian) were included in the study. The mean BMI ranged from 25 ± 4 to 30 ± 6 kg/m² and mean age ranged from 64 ± 8 to 71 ± 10 years. For the Chinese and Indian patients, diagnostic parameters are presented using BMI threshold of 27.5 kg/m² with the area under curve to predict moderate-to-severe OSA being 0.709 (0.665-0.753) and 0.722 (0.635-0.808), respectively. For the Malay and Caucasian, diagnostic parameters are presented using BMI threshold of 35 kg/m² with the area under curve for predicting moderate-to-severe OSA being 0.645 (0.572-0.720) and 0.657 (0.578-0.736), respectively. Balancing the sensitivity and specificity, the optimal STOP-Bang thresholds for the Chinese, Indian, Malay, and Caucasian groups were determined to be 4 or greater.

    CONCLUSIONS: For predicting moderate-to-severe OSA, we recommend BMI threshold of 27.5 kg/m² for Chinese and Indian patients and 35 kg/m² for Malay and Caucasian patients. The optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian groups is 4 or greater.

    CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Postoperative Vascular Events in Unrecognized Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/study/NCT01494181; Identifier: NCT01494181.

  2. Day AC, Cooper D, Burr J, Foster PJ, Friedman DS, Gazzard G, et al.
    Br J Ophthalmol, 2018 12;102(12):1658-1662.
    PMID: 29453222 DOI: 10.1136/bjophthalmol-2017-311447
    BACKGROUND: To describe the surgical technique and refractive outcomes following clear lens extraction (CLE) in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction trial.

    METHODS: Review of prospectively collected data from a multicentre, randomised controlled trial comparing CLE and laser peripheral iridotomy. Eligible participants were ≥50 years old and newly diagnosed with (1) primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and refractive outcomes at 12 and 36 months postoperatively for those who underwent CLE.

    RESULTS: Of the 419 participants, 208 were randomised to CLE. Mean baseline CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months. Fifty-nine per cent and 85% eyes were within ±0.5D and ±1.0D of predicted refraction, respectively, at 36 months.

    CONCLUSIONS: Mean CDVA in patients undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study period. Refractive error was significantly reduced with surgery but refractive predictability was suboptimal.

    TRIAL REGISTRATION NUMBER:

  3. Edwards FA, Finan J, Graham LK, Larsen TH, Wilcove DS, Hsu WW, et al.
    Biol Conserv, 2017 Jan;205:85-92.
    PMID: 28133389 DOI: 10.1016/j.biocon.2016.11.011
    The demand for timber products is facilitating the degradation and opening up of large areas of intact habitats rich in biodiversity. Logging creates an extensive network of access roads within the forest, yet these are commonly ignored or excluded when assessing impacts of logging on forest biodiversity. Here we determine the impact of these roads on the overall condition of selectively logged forests in Borneo, Southeast Asia. Focusing on dung beetles along > 40 km logging roads we determine: (i) the magnitude and extent of edge effects alongside logging roads; (ii) whether vegetation characteristics can explain patterns in dung beetle communities, and; (iii) how the inclusion of road edge forest impacts dung beetle assemblages within the overall logged landscape. We found that while vegetation structure was significantly affected up to 34 m from the road edge, impacts on dung beetle communities penetrated much further and were discernible up to 170 m into the forest interior. We found larger species and particularly tunnelling species responded more than other functional groups which were also influenced by micro-habitat variation. We provide important new insights into the long-term ecological impacts of tropical logging. We also support calls for improved logging road design both during and after timber extraction to conserve more effectively biodiversity in production forests, for instance, by considering the minimum volume of timber, per unit length of logging road needed to justify road construction. In particular, we suggest that governments and certification bodies need to highlight more clearly the biodiversity and environmental impacts of logging roads.
  4. Zhao D, Kim MH, Pastor-Barriuso R, Chang Y, Ryu S, Zhang Y, et al.
    PLoS One, 2016;11(1):e0146057.
    PMID: 26731527 DOI: 10.1371/journal.pone.0146057
    IMPORTANCE: Intraocular pressure (IOP) reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma.

    OBJECTIVE: To examine the associations of change in body mass index (BMI), waist circumference, and percent fat mass with change in intraocular pressure (IOP) in a large sample of Korean adults.

    DESIGN, SETTING AND PARTICIPANTS: Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits).

    EXPOSURES: BMI, waist circumference, and percent fat mass.

    MAIN OUTCOME MEASURE(S): At each visit, IOP was measured in both eyes with automated noncontact tonometers.

    RESULTS: In multivariable-adjusted models, the average increase in IOP (95% confidence intervals) over time per interquartile increase in BMI (1.26 kg/m2), waist circumference (6.20 cm), and percent fat mass (3.40%) were 0.18 mmHg (0.17 to 0.19), 0.27 mmHg (0.26 to 0.29), and 0.10 mmHg (0.09 to 0.11), respectively (all P < 0.001). The association was stronger in men compared to women (P < 0.001) and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model.

    CONCLUSIONS AND RELEVANCE: Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  5. Zhao D, Kim MH, Pastor-Barriuso R, Chang Y, Ryu S, Zhang Y, et al.
    Invest Ophthalmol Vis Sci, 2014 Oct;55(10):6244-50.
    PMID: 25183763 DOI: 10.1167/iovs.14-14151
    To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women.
  6. Sodhi NS, Wilcove DS, Lee TM, Sekercioglu CH, Subaraj R, Bernard H, et al.
    Conserv Biol, 2010 Oct;24(5):1290-8.
    PMID: 20345403 DOI: 10.1111/j.1523-1739.2010.01495.x
    There are few empirical data, particularly collected simultaneously from multiple sites, on extinctions resulting from human-driven land-use change. Southeast Asia has the highest deforestation rate in the world, but the resulting losses of biological diversity remain poorly documented. Between November 2006 and March 2008, we conducted bird surveys on six landbridge islands in Malaysia and Indonesia. These islands were surveyed previously for birds in the early 1900 s, when they were extensively forested. Our bird inventories of the islands were nearly complete, as indicated by sampling saturation curves and nonparametric true richness estimators. From zero (Pulau Malawali and Pulau Mantanani) to 15 (Pulau Bintan) diurnal resident landbird species were apparently extirpated since the early 1900 s. Adding comparable but published extinction data from Singapore to our regression analyses, we found there were proportionally fewer forest bird extinctions in areas with greater remaining forest cover. Nevertheless, the statistical evidence to support this relationship was weak, owing to our unavoidably small sample size. Bird species that are restricted to the Indomalayan region, lay few eggs, are heavier, and occupy a narrower habitat breadth, were most vulnerable to extinction on Pulau Bintan. This was the only island where sufficient data existed to analyze the correlates of extinction. Forest preservation and restoration are needed on these islands to conserve the remaining forest avifauna. Our study of landbridge islands indicates that deforestation may increasingly threaten Southeast Asian biodiversity.
  7. Akhtar Z, Gallagher MM, Yap YG, Leung LWM, Elbatran AI, Madden B, et al.
    Pacing Clin Electrophysiol, 2021 05;44(5):875-882.
    PMID: 33792080 DOI: 10.1111/pace.14232
    BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc).

    METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19.

    RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p 455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]).

    CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

  8. Makharia G, Gibson PR, Bai JC, Karakan T, Lee YY, Collins L, et al.
    J Clin Gastroenterol, 2022 Jan 01;56(1):1-15.
    PMID: 34860201 DOI: 10.1097/MCG.0000000000001588
  9. Agarwal S, Prasad S, Agarwal A, Raja Ali RA, Leffler DA, Green PHR, et al.
    PMID: 39528309 DOI: 10.1111/jgh.16793
    BACKGROUND AND AIM: Celiac disease (CeD) is increasingly diagnosed but significant disparities exist in awareness, practices, resources, and legislation worldwide. We conducted a global online survey with CeD experts to assess this disparity internationally.

    METHODS: A 55 questions survey encompassing nine domains relevant to CeD care (awareness, gluten-free [GF] foods availability/cost/quality, GF labeling, CeD dietician availability, insurance for CeD patients, medical training, research funding, patient support groups, and unmet needs) was generated and sent to CeD experts worldwide electronically. Countries were stratified based on per capita income as high-income (HIC) and lower-income countries (LIC) (including upper-middle-, lower-middle-, and low-income countries). Survey responses were summarized as a single score using principal component analysis.

    RESULTS: Valid responses were obtained from 131(37.4%) [HIC: 71; LIC: 60] of contacted CeD experts from 63 countries. Compared with HIC, LIC experts perceived worse availability (HIC:80% vs LIC: 47%; P 

  10. Hui DSC, Yeboah-Manu D, Nachega JB, Rodriguez-Morales AJ, Traore T, Maeurer M, et al.
    Lancet Respir Med, 2025 Jan;13(1):11-14.
    PMID: 39608386 DOI: 10.1016/S2213-2600(24)00382-5
  11. Akshayaa L, Lakshmi T, Devaraj E, Roy A, Raghunandhakumar S, Sivaperumal P, et al.
    Bioinformation, 2020;16(11):878-881.
    PMID: 34803262 DOI: 10.6026/97320630016878
    Design and development of effective anti-virals in combating CoVid-19 is a great challenge worldwide. Known drugs such as chloroquine, lopinavir, favipiravir and remdesivir are used in the management of CoVid - 19. It is known that Ivermectin and remdesivir both are effective against filoviruses, paramyxo viruses. Available data also shows that ivermectin and remedesivir repress the replication of SARS-CoV-2. Thus, we document the potential use of ivermectin and remdesivir in the management of CoVid -19.
  12. Hui DS, Ip M, Ling T, Chang SC, Liao CH, Yoo CG, et al.
    Respirology, 2011 Apr;16(3):532-9.
    PMID: 21299688 DOI: 10.1111/j.1440-1843.2011.01943.x
    Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries.
  13. Wu YL, Lee V, Liam CK, Lu S, Park K, Srimuninnimit V, et al.
    Lung Cancer, 2018 12;126:1-8.
    PMID: 30527172 DOI: 10.1016/j.lungcan.2018.10.004
    OBJECTIVE: Patients with advanced non-small-cell lung cancer (NSCLC) with an adenocarcinoma component are recommended to undergo epidermal growth factor receptor (EGFR) mutation testing when being considered for EGFR targeted therapy. We conducted an exploratory analysis to inform the clinical utility of EGFR mutation testing in blood cell-free DNA using the cobas®EGFR Mutation Test v2.

    MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.

    RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.

    CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.

  14. Edwards DP, Magrach A, Woodcock P, Ji Y, Lim NT-, Edwards FA, et al.
    Ecol Appl, 2014;24(8):2029-49.
    PMID: 29185670 DOI: 10.1890/14-0010.1
    Strong global demand for tropical timber and agricultural products has driven large-scale logging and subsequent conversion of tropical forests. Given that the majority of tropical landscapes have been or will likely be logged, the protection of biodiversity within tropical forests thus depends on whether species can persist in these economically exploited lands, and if species cannot persist, whether we can protect enough primary forest from logging and conversion. However, our knowledge of the impact of logging and conversion on biodiversity is limited to a few taxa, often sampled in different locations with complex land-use histories, hampering attempts to plan cost-effective conservation strategies and to draw conclusions across taxa. Spanning a land-use gradient of primary forest, once- and twice-logged forests, and oil palm plantations, we used traditional sampling and DNA metabarcoding to compile an extensive data set in Sabah, Malaysian Borneo for nine vertebrate and invertebrate taxa to quantify the biological impacts of logging and oil palm, develop cost-effective methods of protecting biodiversity, and examine whether there is congruence in response among taxa. Logged forests retained high species richness, including, on average, 70% of species found in primary forest. In contrast, conversion to oil palm dramatically reduces species richness, with significantly fewer primary-forest species than found on logged forest transects for seven taxa. Using a systematic conservation planning analysis, we show that efficient protection of primary-forest species is achieved with land portfolios that include a large proportion of logged-forest plots. Protecting logged forests is thus a cost-effective method of protecting an ecologically and taxonomically diverse range of species, particularly when conservation budgets are limited. Six indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies, and true bugs) proved to be consistently good predictors of the response of the other taxa to logging and oil palm. Our results confidently establish the high conservation value of logged forests and the low value of oil palm. Cross-taxon congruence in responses to disturbance also suggests that the practice of focusing on key indicator taxa yields important information of general biodiversity in studies of logging and oil palm.
  15. Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, et al.
    Kidney Int, 2022 Dec;102(6):1228-1237.
    PMID: 36411019 DOI: 10.1016/j.kint.2022.07.012
    Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.
  16. Awan AAY, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, et al.
    Ann Intern Med, 2023 Dec;176(12):1648-1655.
    PMID: 38079642 DOI: 10.7326/M23-2391
    DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO.

    METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.

    RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

  17. Chan MTV, Wang CY, Seet E, Tam S, Lai HY, Chew EFF, et al.
    JAMA, 2019 May 14;321(18):1788-1798.
    PMID: 31087023 DOI: 10.1001/jama.2019.4783
    IMPORTANCE: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain.

    OBJECTIVES: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.

    DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.

    EXPOSURES: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.

    MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.

    RESULTS: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P 

  18. Ji Y, Ashton L, Pedley SM, Edwards DP, Tang Y, Nakamura A, et al.
    Ecol Lett, 2013 Oct;16(10):1245-57.
    PMID: 23910579 DOI: 10.1111/ele.12162
    To manage and conserve biodiversity, one must know what is being lost, where, and why, as well as which remedies are likely to be most effective. Metabarcoding technology can characterise the species compositions of mass samples of eukaryotes or of environmental DNA. Here, we validate metabarcoding by testing it against three high-quality standard data sets that were collected in Malaysia (tropical), China (subtropical) and the United Kingdom (temperate) and that comprised 55,813 arthropod and bird specimens identified to species level with the expenditure of 2,505 person-hours of taxonomic expertise. The metabarcode and standard data sets exhibit statistically correlated alpha- and beta-diversities, and the two data sets produce similar policy conclusions for two conservation applications: restoration ecology and systematic conservation planning. Compared with standard biodiversity data sets, metabarcoded samples are taxonomically more comprehensive, many times quicker to produce, less reliant on taxonomic expertise and auditable by third parties, which is essential for dispute resolution.
  19. Guerra GR, Kong JC, Millen RM, Read M, Liu DS, Roth S, et al.
    Cell Death Dis, 2021 Oct 18;12(11):959.
    PMID: 34663790 DOI: 10.1038/s41419-021-04141-5
    Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
  20. Huneke NTM, Amin J, Baldwin DS, Bellato A, Brandt V, Chamberlain SR, et al.
    Mol Psychiatry, 2024 Dec;29(12):3915-3925.
    PMID: 38914807 DOI: 10.1038/s41380-024-02638-x
    There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
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