Displaying publications 1 - 20 of 118 in total

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  1. Munajat M, Mohd Nordin NA, Mohamad Yahya NH, Zulkifly AH
    Medicine (Baltimore), 2019 Sep;98(36):e17045.
    PMID: 31490397 DOI: 10.1097/MD.0000000000017045
    INTRODUCTION: The presence of significant pain and swelling during the acute stage following total knee arthroplasty (TKA) may limit the patients' ability to cooperate in intensive physiotherapy interventions. Low-intensity pulsed ultrasound is one of the modalities that can be used for acute pain and swelling management. However, only one study investigated the effect of this modality in patients with TKA. There is limited documentation of the effects of combining low-intensity pulsed ultrasound in TKA rehabilitation in the recovery of physical impairments and how these influence the recovery of function after TKA. Therefore, this study is proposed with the aim to evaluate the effects of low-intensity pulsed ultrasound as an adjunct to conventional physiotherapy on the recovery of physical impairments, functional performance and quality of life after TKA surgery.

    METHODS: This is an assessor-blinded quasi-experimental study comparing two approaches of physiotherapy, namely pulsed ultrasound-added physiotherapy and conventional physiotherapy. Total number of participants with TKA required for this study will be calculated based on the result of a pilot study. Participants will be alternately allocated into either pulsed ultrasound-added physiotherapy group (low-intensity pulsed ultrasound and conventional physiotherapy) or control group (conventional physiotherapy). Pulsed ultrasound-added physiotherapy group will receive low-intensity pulsed ultrasound starting at post-operative day 2 (4-5 times for the first-week after surgery and 2-3 times a week for a further 2 weeks). Both groups will receive conventional physiotherapy 4 to 5 times for the first-week after surgery and 2 to 3 times a week for a further 11 weeks. This procedure and process will be tested and established in a pilot study. Primary outcomes of interest are pain level, swelling, active range of knee motion, and quadriceps strength. The secondary outcomes are functional performance and quality of life.

    DISCUSSION: This study will fill the gaps in knowledge relating the benefits of including low-intensity pulsed ultrasound into conventional physiotherapy for patients with TKA.

    TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001226291.

  2. Chen TH, Yen AM, Fann JC, Gordon P, Chen SL, Chiu SY, et al.
    Medicine (Baltimore), 2017 Jan;96(3):e5684.
    PMID: 28099330 DOI: 10.1097/MD.0000000000005684
    BACKGROUND: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality.

    METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.

    RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.

    CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

  3. Kong YC, Bhoo-Pathy N, O'Rorke M, Subramaniam S, Bhoo-Pathy NT, See MH, et al.
    Medicine (Baltimore), 2020 Feb;99(6):e19093.
    PMID: 32028433 DOI: 10.1097/MD.0000000000019093
    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 
  4. Ghazali WSW, Daud SMM, Mohammad N, Wong KK
    Medicine (Baltimore), 2018 Oct;97(42):e12787.
    PMID: 30334968 DOI: 10.1097/MD.0000000000012787
    The aims of this study were to determine damage index in systemic lupus erythematosus (SLE) patients based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) and to determine the laboratory and clinico-demographic factors affecting SDI.This is a retrospective cohort study of 94 SLE patients attending rheumatology clinics in 2 local hospitals in Kelantan, Malaysia. The patients were divided into 2 groups based on SDI score assigned by the attending physician, 0 (without damage) or ≥1 (with damage). Newly diagnosed SLE patients with disease duration less than 6 months were excluded.A total of 45 (47.9%) SLE patients showed damage by SDI score. Majority of the subjects had neuropsychiatric damages (21/94; 22.3%) followed by skin (12/94; 12.8%) and musculoskeletal (6/94; 6.4%) damage. SDI score was significantly associated with higher disease duration (6.2 ± 6.57 years vs 4.5 ± 3.7 years; P = .018), lower prednisolone dose (8.74 ± 10.89 mg vs 4.89 ± 3.81 mg; P 
  5. Lee SW, Lee JY, Tan CS, Wong CP
    Medicine (Baltimore), 2016 Jan;95(2):e2457.
    PMID: 26765440 DOI: 10.1097/MD.0000000000002457
    Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims.To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan.A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitted separately, combining direct and indirect evidence for each comparison.Twenty-nine studies, 16 RCTs and 13 observational studies each met the inclusion criteria. The most common strategy used was drug changes during the Ramadan period, which found that the use of DPP-4 (Dipeptidyl peptidase inhibitor -4) inhibitors were associated with a reduction in incidence of experiencing hypoglycemia during Ramadan in both RCTs (pooled relative risk: 0.56; 95% confidence interval: 0.44-0.72) as well as in observational studies (pooled relative risk: 0.27; 0.09-0.75). Ramadan-focused education was shown to be beneficial in reducing hypoglycemia in observational studies but not RCTs (0.25 versus 1.00). Network meta-analyses suggest that incretin mimetics can reduce the risk of hypoglycemia by nearly 1.5 times.The newer antidiabetic agents appear to lower the risk of hypoglycemia and improved glycemic control when compared with sulfonylureas. Ramadan-focused education shows to be a promising strategy but more rigorous examination from RCTs are required.
  6. Alshareefy Y, Cummins S, Mazzoleni A, Sharma V, Guggilapu S, Leong AWY, et al.
    Medicine (Baltimore), 2023 Nov 17;102(46):e36094.
    PMID: 37986400 DOI: 10.1097/MD.0000000000036094
    Pancreatic neuroendocrine tumors (PanNETs) are a rare subtype of pancreatic cancer and can be divided into functional (30-40%) and nonfunctional subtypes. The different subtypes of functional PanNETs (F-PanNETs) have a variety of classical presentations that raise suspicion for an underlying PanNET. It is estimated that 90% of PanNETs are sporadic, and the PI3K-Akt-mTOR and ATRX/DAXX signaling pathways have been recognized as key genetic pathways implicated in the pathogenesis. The other 10% of PanNETs may occur in the context of familial cancer syndromes such as MEN1. Chromogranin A is the most useful biomarker currently; however, several studies have shown limitations with its use, especially its prognostic value. Synaptophysin is a novel biomarker which has shown promising preliminary results however its use clinically has yet to be established. Blood tests assessing hormone levels, cross-sectional imaging, and endoscopic ultrasound remain at the core of establishing a diagnosis of F-PanNET. The treatment options for F-PanNETs include surgical methods such as enucleation, systemic therapies like chemotherapy and novel targeted therapies such as everolimus. The prognosis for F-PanNETs is more favorable than for nonfunctional PanNETs, however metastatic disease is associated with poor survival outcomes. Researchers should also focus their efforts on identifying novel pathways implicated in the pathogenesis of F-PanNETs in order to develop new targeted therapies that may reduce the need for surgical intervention and on the establishment of novel biomarkers that may reduce the need for invasive testing and allow for earlier detection of F-PanNETs.
  7. Choo MM, Yeong CM, Grigg JR, Khaliddin N, Kadir AJ, Barnes EH, et al.
    Medicine (Baltimore), 2018 Nov;97(48):e13357.
    PMID: 30508927 DOI: 10.1097/MD.0000000000013357
    To report observations of horizontal corneal diameter (HCD) and central corneal thickness (CCT) changes in premature infants with stable optic disc cupping and intraocular pressures (IOPs). The HCD and CCT at term serve as a baseline for premature infants.Sixty-three premature infants were enrolled in a prospective case series. HCD, CCT, and IOP were measured. RetCam images of the optic discs were used to evaluate the cup-disc ratio (CDR) and read by an independent masked observer. Data were collected at between preterm (32-36 weeks) and again at term (37-41 weeks) postconceptual age. Left eye measurements were used for statistical analysis. Left eye findings were combined to construct predictive models for HCD and CCT.The mean HCD was 9.1 mm (standard deviation [SD] = 0.7 mm) at preterm and 10.0 mm (SD = 0.52 mm) at term. The mean CCT preterm was 618.8 (SD = 72.9) μm and at term 563.9 (SD = 50.7) μm, respectively. The average preterm CDR was 0.31 and at maturity was 0.33. Average IOP of preterm and term was 13.1 and 14.11 mm Hg, respectively. There was significant linear correlation between HCD with the postmenstrual age (r = 0.40, P 
  8. Thanaviratananich S, Cho SH, Ghoshal AG, Abdul Muttalif AR, Lin HC, Pothirat C, et al.
    Medicine (Baltimore), 2016 Jul;95(28):e4090.
    PMID: 27755477
    Asia-Pacific Burden of Respiratory Diseases (APBORD) was a cross-sectional, observational study examining the burden of respiratory disease in adults across 6 Asia-Pacific countries.This article reports symptoms, healthcare resource utilization (HCRU), work impairment and cost burden associated with allergic rhinitis (AR), asthma, chronic obstructive pulmonary disease (COPD), and rhinosinusitis in Thailand.Consecutive participants aged ≥18 years with a primary diagnosis of AR, asthma, COPD, or rhinosinusitis were enrolled at 4 hospitals in Thailand during October 2012 and October 2013. Participants completed a survey detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Locally sourced unit costs were used in the calculation of total costs.The study enrolled 1000 patients. The most frequent primary diagnosis was AR (44.2%), followed by rhinosinusitis (24.1%), asthma (23.7%), and COPD (8.0%). Overall, 316 (31.6%) of patients were diagnosed with some combination of the 4 diseases. Blocked nose or congestion (17%) and cough or coughing up phlegm (16%) were the main reasons for the current medical visit. The mean annual cost for patients with a respiratory disease was US$1495 (SD 3133) per patient. Costs associated with work productivity loss were the principal contributor for AR and rhinosinusitis patients while medication costs were the highest contributor for asthma and COPD patients.The study findings highlight the burden associated with 4 prevalent respiratory diseases in Thailand. Thorough investigation of concomitant conditions and improved disease management may help to reduce the burden of these respiratory diseases.
  9. Lin HC, Cho SH, Ghoshal AG, Muttalif ARBA, Thanaviratananich S, Bagga S, et al.
    Medicine (Baltimore), 2016 Jul;95(27):e3854.
    PMID: 27399064 DOI: 10.1097/MD.0000000000003854
    Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of Respiratory Diseases (APBORD) study was a cross-sectional, observational study which examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across Asia-Pacific using 1 standard protocol. Here we report symptoms, healthcare resource use (HCRU), work impairment, and associated cost in Taiwan.Consecutive participants aged ≥ 18 years presenting to a physician with symptoms meeting the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Participants and their treating physician completed surveys detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Costs including direct medical costs and indirect costs associated with lost work productivity were calculated.The study enrolled 1001 patients. AR was the most frequent primary diagnosis (31.2%). A quarter of patients presented with a combination of respiratory diseases, with AR and asthma being the most frequent combination (14.1%). Cough or coughing up phlegm was the primary reason for the medical visit for patients with asthma and COPD, whereas nasal symptoms (watery runny nose, blocked nose, and congestion) were the primary reasons for AR and rhinosinusitis. Specialists were the most frequently used healthcare resource by patients with AR (26.1%), asthma (26.4%), COPD (26.6%), and rhinosinusitis (47.3%). The mean annual cost per patient with a respiratory disease was US$4511 (SD 5395). The cost was almost double for employed patients (US$8047, SD 6175), with the majority attributable to lost productivity.Respiratory diseases have a significant impact on disease burden in Taiwan. Treatment strategies that prevent lost work productivity could greatly reduce the economic burden of these diseases.
  10. Thanaviratananich S, Cho SH, Ghoshal AG, Muttalif ARBA, Lin HC, Pothirat C, et al.
    Medicine (Baltimore), 2016 Jul;95(28):e4090.
    PMID: 27428193 DOI: 10.1097/MD.0000000000004090
    Asia-Pacific Burden of Respiratory Diseases (APBORD) was a cross-sectional, observational study examining the burden of respiratory disease in adults across 6 Asia-Pacific countries.This article reports symptoms, healthcare resource utilization (HCRU), work impairment and cost burden associated with allergic rhinitis (AR), asthma, chronic obstructive pulmonary disease (COPD), and rhinosinusitis in Thailand.Consecutive participants aged ≥18 years with a primary diagnosis of AR, asthma, COPD, or rhinosinusitis were enrolled at 4 hospitals in Thailand during October 2012 and October 2013. Participants completed a survey detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Locally sourced unit costs were used in the calculation of total costs.The study enrolled 1000 patients. The most frequent primary diagnosis was AR (44.2%), followed by rhinosinusitis (24.1%), asthma (23.7%), and COPD (8.0%). Overall, 316 (31.6%) of patients were diagnosed with some combination of the 4 diseases. Blocked nose or congestion (17%) and cough or coughing up phlegm (16%) were the main reasons for the current medical visit. The mean annual cost for patients with a respiratory disease was US$1495 (SD 3133) per patient. Costs associated with work productivity loss were the principal contributor for AR and rhinosinusitis patients while medication costs were the highest contributor for asthma and COPD patients.The study findings highlight the burden associated with 4 prevalent respiratory diseases in Thailand. Thorough investigation of concomitant conditions and improved disease management may help to reduce the burden of these respiratory diseases.
  11. Lee KW, Chien TW, Yeh YT, Chou W, Wang HY
    Medicine (Baltimore), 2021 Mar 12;100(10):e24749.
    PMID: 33725830 DOI: 10.1097/MD.0000000000024749
    BACKGROUND: During the COVID-19 pandemic, one of the frequently asked questions is which countries (or continents) are severely hit. Aside from using the number of confirmed cases and the fatality to measure the impact caused by COVID-19, few adopted the inflection point (IP) to represent the control capability of COVID-19. How to determine the IP days related to the capability is still unclear. This study aims to (i) build a predictive model based on item response theory (IRT) to determine the IP for countries, and (ii) compare which countries (or continents) are hit most.

    METHODS: We downloaded COVID-19 outbreak data of the number of confirmed cases in all countries as of October 19, 2020. The IRT-based predictive model was built to determine the pandemic IP for each country. A model building scheme was demonstrated to fit the number of cumulative infected cases. Model parameters were estimated using the Solver add-in tool in Microsoft Excel. The absolute advantage coefficient (AAC) was computed to track the IP at the minimum of incremental points on a given ogive curve. The time-to-event analysis (a.k.a. survival analysis) was performed to compare the difference in IPs among continents using the area under the curve (AUC) and the respective 95% confidence intervals (CIs). An online comparative dashboard was created on Google Maps to present the epidemic prediction for each country.

    RESULTS: The top 3 countries that were hit severely by COVID-19 were France, Malaysia, and Nepal, with IP days at 263, 262, and 262, respectively. The top 3 continents that were hit most based on IP days were Europe, South America, and North America, with their AUCs and 95% CIs at 0.73 (0.61-0.86), 0.58 (0.31-0.84), and 0.54 (0.44-0.64), respectively. An online time-event result was demonstrated and shown on Google Maps, comparing the IP probabilities across continents.

    CONCLUSION: An IRT modeling scheme fitting the epidemic data was used to predict the length of IP days. Europe, particularly France, was hit seriously by COVID-19 based on the IP days. The IRT model incorporated with AAC is recommended to determine the pandemic IP.

  12. Naing C, Sandhu NK, Wai VN
    Medicine (Baltimore), 2016 Apr;95(14):e3205.
    PMID: 27057848 DOI: 10.1097/MD.0000000000003205
    Malaria and human immunodeficiency virus (HIV) infections are globally important public health concerns. The objectives of this study were (i) to determine the prevalence of malaria and HIV co-infections in people living in endemic countries, and (ii) to assess the effect of co-infection on anemia.Studies were searched on electronic databases including PubMed, Embase, Medline, Google Scholar, and African Journals Online. Observational studies, assessing the prevalence of co-infection and reporting its association with anemia, were included. The methodological quality of included studies was assessed using a tool called the risk of bias assessment for non-randomized studies. Heterogeneity among studies was investigated with the I-square test. Pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effect model, reflected on heterogeneity among studies. Summary odds ratio (OR), summary standardized mean difference (SMD), and their corresponding 95% CIs were estimated, as appropriate. Subgroup analysis and meta-regression were performed for robustness of results. Publication bias was assessed by visualization of a funnel plot.Twenty-three studies were included in the present study. Overall, the pooled prevalence of co-infection was 19% (95% CI: 15-23%, I: 98.1%), showing 26% (95% CI: 20-32%, I: 98.7%) in adults, 12% (95% CI: 7-17%, I: 95.0) in pregnant women, and 9% (95% CI: 6-11%, I: 68.6%) in children. Anemia was comparable between the monoinfected and co-infected adults (summary OR: 1.49, 95% CI: 0.93-2.37) and increased by 49% in co-infected pregnant women (summary OR: 1.49, 95% CI: 1.14-1.94). The mean hemoglobin concentration was significantly lower in the co-infected group than the monoinfected group (summary SMD: -0.47, 95% CI: -0.61 to -0.33). The results of meta-regression on the prevalence of co-infection using the publication year and total population as covariates showed the I value remained high implying a de facto random distribution of heterogeneity. An asymmetrical funnel plot indicated the presence of publication bias. Due to heterogeneity of the studies in this review, the results have to be interpreted with caution.The findings of this study suggest that the prevalence of malaria and HIV co-infection, particularly in pregnant women, requires special attention from healthcare personnel. Better understanding of the co-infection is crucial for designing treatment strategies. Future well-powered, prospective designs assessing the interaction between malaria and HIV are recommended.
  13. Mamada H, Murayama A, Ozaki A, Hashimoto T, Saito H, Sawano T, et al.
    Medicine (Baltimore), 2023 Jan 27;102(4):e32776.
    PMID: 36705373 DOI: 10.1097/MD.0000000000032776
    This cross-sectional analysis aimed to assess the extent of conflicts of interest among the Japanese government coronavirus disease 2019 (COVID-19) advisory board members and elucidate the accuracy of conflicts of interest (COI) disclosure and management strategies. Using the payment data from all 79 pharmaceutical companies in Japan between 2017 and 2019 and direct research grants from the Japanese government between 2019 and 2020, we evaluated the extent of financial and non-financial COI among all 20 Japanese government COVID-19 advisory board members. The Ethic Committee of the Medical Governance Research Institute approved this study. Japanese government COVID-19 advisory board members were predominantly male (75.0%) and physicians (50.0%). Between 2019 and 2020, 2 members (10.0%) received a total of $819,244 in government research funding. Another 5 members (25.0%) received $532,127 in payments, including $276,722 in personal fees, from 31 pharmaceutical companies between 2017 and 2019. The average value of the pharmaceutical payments was $9155 (standard deviation: $12,975). Furthermore, neither the Ministry of Health, Labor, and Welfare nor the Japanese Cabinet Secretariat disclosed financial or non-financial COI with industry. Additionally, the government had no policies for managing COI among advisory board members. This study found that the Japanese government COVID-19 advisory board had financial and non-financial COI with pharmaceutical companies and the government. Furthermore, personal communication received as part of this research indicated that there were no rigorous COI management strategies for the COVID-19 advisory board members. Any government must ensure the independence of scientific advisory boards by implementing more rigorous and transparent management strategies that require the declaration and public disclosure of all COI.
  14. Md Radzi AB, Tan SS
    Medicine (Baltimore), 2018 Jan;97(4):e8884.
    PMID: 29369168 DOI: 10.1097/MD.0000000000008884
    RATIONALE: We report a rare case of hepatocellular carcinoma (HCC) with metastases to the mandible and coracoid process of scapula without evidence of lung involvement.

    PATIENTS CONCERNS: The patient was diagnosed with HCC, presented 5 months later with right lower tooth pain, swelling over the right mandible area and right shoulder pain.

    DIAGNOSES: Histopathological examination of mandible showed findings suggestive of metastatic HCC. Magnetic resonance imaging (MRI) of the right shoulder revealed findings of irregular enhancing lesion at the right coracoid process causing erosion of the coracoid process.

    INTERVENTIONS: Patient was subsequently referred for palliative medicine care.

    OUTCOMES: He received adequate analgesia.

    LESSONS: Oral cavity and scapula metastases from HCC are very rare. Most oral metastases are associated with lung metastases, and they possibly occur by hematogenous route. In our case, the possible pathway of metastasis is an anastomotic network of paravertebral veins that bypasses the pulmonary, inferior caval, and portal venous circulations.

  15. Imon RR, Aktar S, Morshed N, Nur SM, Mahtarin R, Rahman FA, et al.
    Medicine (Baltimore), 2023 Nov 10;102(45):e35347.
    PMID: 37960765 DOI: 10.1097/MD.0000000000035347
    Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has long been found to be dysregulated in human lung adenocarcinomas (LUADs). Nevertheless, the function, mutational profile, epigenetic regulation, co-expression profile, and clinicopathological significance of the GPC3 gene in LUAD progression are not well understood. In this study, we analyzed cancer microarray datasets from publicly available databases using bioinformatics tools to elucidate the above parameters. We observed significant downregulation of GPC3 in LUAD tissues compared to their normal counterparts, and this downregulation was associated with shorter overall survival (OS) and relapse-free survival (RFS). Nevertheless, no significant differences in the methylation pattern of GPC3 were observed between LUAD and normal tissues, although lower promoter methylation was observed in male patients. GPC3 expression was also found to correlate significantly with infiltration of B cells, CD8+, CD4+, macrophages, neutrophils, and dendritic cells in LUAD. In addition, a total of 11 missense mutations were identified in LUAD patients, and ~1.4% to 2.2% of LUAD patients had copy number amplifications in GPC3. Seventeen genes, mainly involved in dopamine receptor-mediated signaling pathways, were frequently co-expressed with GPC3. We also found 11 TFs and 7 miRNAs interacting with GPC3 and contributing to disease progression. Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD.
  16. Goh CH, Ng SC, Kamaruzzaman SB, Chin AV, Poi PJ, Chee KH, et al.
    Medicine (Baltimore), 2016 May;95(19):e3614.
    PMID: 27175670 DOI: 10.1097/MD.0000000000003614
    To evaluate the utility of blood pressure variability (BPV) calculated using previously published and newly introduced indices using the variables falls and age as comparators.While postural hypotension has long been considered a risk factor for falls, there is currently no documented evidence on the relationship between BPV and falls.A case-controlled study involving 25 fallers and 25 nonfallers was conducted. Systolic (SBPV) and diastolic blood pressure variability (DBPV) were assessed using 5 indices: standard deviation (SD), standard deviation of most stable continuous 120 beats (staSD), average real variability (ARV), root mean square of real variability (RMSRV), and standard deviation of real variability (SDRV). Continuous beat-to-beat blood pressure was recorded during 10 minutes' supine rest and 3 minutes' standing.Standing SBPV was significantly higher than supine SBPV using 4 indices in both groups. The standing-to-supine-BPV ratio (SSR) was then computed for each subject (staSD, ARV, RMSRV, and SDRV). Standing-to-supine ratio for SBPV was significantly higher among fallers compared to nonfallers using RMSRV and SDRV (P = 0.034 and P = 0.025). Using linear discriminant analysis (LDA), 3 indices (ARV, RMSRV, and SDRV) of SSR SBPV provided accuracies of 61.6%, 61.2%, and 60.0% for the prediction of falls which is comparable with timed-up and go (TUG), 64.4%.This study suggests that SSR SBPV using RMSRV and SDRV is a potential predictor for falls among older patients, and deserves further evaluation in larger prospective studies.
  17. Goh CH, Ng SC, Kamaruzzaman SB, Chin AV, Tan MP
    Medicine (Baltimore), 2017 Oct;96(42):e8193.
    PMID: 29049203 DOI: 10.1097/MD.0000000000008193
    The aim of this study was to determine the relationship between falls and beat-to-beat blood pressure (BP) variability.Continuous noninvasive BP measurement is as accurate as invasive techniques. We evaluated beat-to-beat supine and standing BP variability (BPV) using time and frequency domain analysis from noninvasive continuous BP recordings.A total of 1218 older adults were selected. Continuous BP recordings obtained were analyzed to determine standard deviation (SD) and root mean square of real variability (RMSRV) for time domain BPV and fast-Fourier transform low frequency (LF), high frequency (HF), total power spectral density (PSD), and LF:HF ratio for frequency domain BPV.Comparisons were performed between 256 (21%) individuals with at least 1 fall in the past 12 months and nonfallers. Fallers were significantly older (P = .007), more likely to be female (P = .006), and required a longer time to complete the Timed-Up and Go test (TUG) and frailty walk test (P ≤ .001). Standing systolic BPV (SBPV) was significantly lower in fallers compared to nonfallers (SBPV-SD, P = .016; SBPV-RMSRV, P = .033; SBPV-LF, P = .003; SBPV-total PSD, P = .012). Nonfallers had significantly higher supine to standing ratio (SSR) for SBPV-SD, SBPV-RMSRV, and SBPV-total PSD (P = .017, P = .013, and P = .009). In multivariate analyses, standing BPV remained significantly lower in fallers compared to nonfallers after adjustment for age, sex, diabetes, frailty walk, and supine systolic BP. The reduction in frequency-domain SSR among fallers was attenuated by supine systolic BP, TUG, and frailty walk.In conclusion, reduced beat-to-beat BPV while standing is independently associated with increased risk of falls. Changes between supine and standing BPV are confounded by supine BP and walking speed.
  18. Tai ML, Nor HM, Kadir KA, Viswanathan S, Rahmat K, Zain NR, et al.
    Medicine (Baltimore), 2016 Jan;95(1):e1997.
    PMID: 26735523 DOI: 10.1097/MD.0000000000001997
    Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients' prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients. Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment. Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days. Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up. Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit. Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.
  19. Abdul Hamid S, Rahmat K, Ramli MT, Fadzli F, Jamaris S, See MH, et al.
    Medicine (Baltimore), 2018 Aug;97(31):e11412.
    PMID: 30075507 DOI: 10.1097/MD.0000000000011412
    Phyllodes tumor or cystosarcoma phyllodes is a rare fibroepithelial neoplasm which arises from the periductal stroma of the breast. They are classified as benign, borderline, and malignant based on the histologic features. However, all phyllodes tumor (PT) subtypes are regarded as having malignant potential and correct diagnosis is important for surgical management and optimal care. This study is a retrospective review of 76 women diagnosed as PT with highlights on the imaging characteristics, pathology, and surgical treatment over a 7-year period in a tertiary medical center of urban population in Malaysia. There were 45 benign, 16 borderline, and 15 malignant PT. The median age for benign PT was 43, borderline 48.5, and malignant 42 years. The Malay ethnic group constitute 52.6% of cases, with 27.6% and 18.4% in Chinese and Indian ethnic groups, respectively. On mammograms, most benign (64.3%) and 33.3% of malignant PT showed high-density lesions. Calcifications were only seen in 2 benign PT. On ultrasound, 86% of benign PT was well-circumscribed whilst 50.0% of malignant PT had irregular outline. Cystic spaces were seen in 40.0% of malignant and 9.5% of benign PT. 80% of malignant PT lesions were heterogenous. Malignant PT demonstrates tumor heterogeneity, cystic spaces, and posterior acoustic enhancement on ultrasound. Half of malignant PT showed regular borders on ultrasound and appear well circumscribed on mammogram. A total of 46 patients had wide local excision or excision biopsy whilst 30 underwent mastectomy as primary treatment. The majority of the borderline and malignant PTs in our study (75.0% and 85.7% respectively) and only 5 out of the 43 (11.6%) benign PT underwent mastectomy. There were 2 tumor recurrence in the benign PT group and 1 case in the borderline and malignant group respectively.
  20. Jamaris S, Jamaluddin J, Islam T, See MH, Fadzli F, Rahmat K, et al.
    Medicine (Baltimore), 2021 May 14;100(19):e25412.
    PMID: 34106588 DOI: 10.1097/MD.0000000000025412
    ABSTRACT: Pre-operative status of axillary lymph node (ALN) in early breast cancer is usually initially assessed by pre-operative ultrasound, followed by ultrasound-guided needle biopsy (UNB) confirmation. Patients with positive nodal status will undergo axillary lymph node dissection (ALND), while those with negative nodal status will have sentinel lymph node biopsy. ALND is associated with higher morbidity than Sentinel lymph node biopsy. The objective of this study is to determine if axillary ultrasound alone without UNB is predictive enough to assign patients to ALND and to identify ultrasound features that are significantly associated with pathologically positive ALN.383 newly diagnosed primary breast cancer patients between 2012 and 2014, and who had undergone pre-operative axillary ultrasound in University Malaya Medical Centre with a complete histopathology report of the axillary surgery were retrospectively reviewed. ALN was considered positive if it had any of these features: cortical thickening > 3 mm, loss of fatty hilum, hypoechoic solid node, mass-like appearance, round shape and lymph node size > 5 mm. Post-operative histopathological reports were then analyzed for nodal involvement.The overall sensitivity, specificity, and accuracy of pre-operative axillary ultrasound in detecting diseased nodes were 45.5%, 80.7%, and 60.3% respectively. The positive (PPV) and negative predictive values were 76.5% and 51.8%. Round shape, loss of fatty hilum and mass-like appearance had the highest PPVs of 87%, 83% and 81.6% respectively and significant odds ratios (ORs) of 5.22 (95% confidence interval [CI]: 1.52 - 17.86), ORs of 4.77 (95% CI: 2.62 - 8.70) and ORs of 4.26 (95% CI: 2.37 - 7.67) respectively (P-value  3 mm was identified to have low PPV at 69.1%, ORs of 1.71 (95% CI: 0.86 - 3.41, P = .126).There are features on axillary ultrasound that confer high PPV for axillary involvement i.e. round shape, loss of fatty hilum, and mass-like appearance. In a low resource setting, these features may benefit from ALND without further pre-operative biopsies. However, pre-operative UNB for features with low PPV that is, cortical thickness > 3 mm should be considered to obviate the unnecessary morbidity associated with ALND.
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