PURPOSE: We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population.
METHODS: Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk.
RESULTS: The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis.
CONCLUSION: Less than half of the study population (44.8%) required BMD for osteoporosis management when age-specific assessment thresholds were applied. Therefore, in more than half, therapeutic decisions can be made without BMD based on these assessment thresholds.
METHODS: This study is a single-center, single-blinded, prospective randomized clinical study. One hundred twenty patients were randomized into two groups (remifentanil vs dexmedetomidine). Demographic characteristics and clinical outcomes, including level of sedation, vital signs, and patient satisfaction were monitored and recorded.
RESULTS: Group R showed a higher mean observer's assessment of alertness/sedation score (3.9 ± 0.7 vs 3.6 ± 0.8; p = 0.008), mean arterial pressure (92.0 ± 12.0 vs 83.0 ± 13.0 mmHg; p
METHODS: Caregivers (n = 59) of children with ALL were allocated to both groups (intervention, n = 29; TAU control, n = 30) via the SNOSE method. The intervention is a physical copy of a 2-week psychosocial self-help guidebook. Scores on the PCL-5, BDI and BAI were recorded at baseline, post-intervention and 1-month follow-up.
RESULTS: There was a statistically significant difference in traumatic stress symptoms post intervention (F(1, 57) = 5.760, p = .020, np2 = 0.093) in favor of the intervention group. No statistical significance was found for its effect at one-month follow-up, overall depression and anxiety.
CONCLUSION: A psychosocial module developed for caregivers of children with ALL was found to be effective in reducing symptoms of traumatic stress and potentially depression. However, the maintenance of its effectiveness and the effectiveness on anxiety requires further study.
MATERIALS AND METHODS: A total of 119 AA patients had been identified from hospital records of the involved sites, namely Queen Elizabeth Hospital in Sabah, Sarawak General Hospital, Sibu Hospital, Miri Hospital and Bintulu Hospital in Sarawak from Jan 2006 to Dec 2017.
RESULTS: The median age at diagnosis was 46 years, and native ethnic group from Sabah, Kadazan-Dusun, recorded the highest percentage of 41.2%, which could be explained by higher frequency of HLA-DRB1*15:01, an alelle linked to increased risk of AA, among this ethnic group. The majority of patients (59.7%) received cyclosporine (CsA) as monotherapy or in combination with other non-IST agents such as danazol, which was instituted in 48.7% of the patients, while a third of them (33.7%) received antithymocyte globulin (ATG) therapy with or without CsA, and 12.4% underwent allogenic SCT. The five-year overall survival (OS) for all AA patients was 76.1%. Elderly patients >60 years old and those with severe disease had more inferior 5-year survival.
CONCLUSION: A prospective study is warranted to determine the true incidence rate, epidemiological distributions, treatment outcome and overall survival of AA patients in Malaysia. Establishment of allogenic SCT in East Malaysia is imperative to make this curative therapy more accessible to patients with severe disease and improve the outcome.
MATERIALS AND METHODS: 18 patients with histologically confirmed early NSCLC (stage I-IIIA) were recruited from October 2019 to January 2021. The serum CEA was measured pre-operatively, and then at 6, 12, 18 and 24 months post-operatively, in conjunction with routine CT and/or CT-PET surveillance scans.
RESULTS: All patients had a curative R0 anatomical resection (lobectomy) with concurrent systematic mediastinal nodal dissection via a uniportal minimally invasive approach under single lung ventilation general anaesthesia. There was no operative, in-hospital or 30-day mortality. 7 patients (39%) had an elevated pre-operative baseline CEA level > 5.0ng/ml. The mean number of nodes sampled intraoperatively was 15. At median follow-up of 42 months, 11/18 (61.1%) patients were recurrence-free. There were no deaths and two recurrences (18.2%) amongst patients with a CEA < 5 (n=11). In the CEA > 5 subgroup (n=7), there were two deaths (28.5%) and 5/7 (71.4%) patients had a radiological recurrence. There was no difference in overall survival however disease-free survival (DFS) was significantly inferior in patients with a baseline CEA > 5. Median DFS was not reached in patients with CEA < 5 and 18 months in those with an elevated CEA > 5 (p<0.001) Conclusion: Almost 40% of local NSCLC patients had an elevated baseline CEA suggesting this is a useful prognostic and surveillance biomarker to incorporate in the routine work-up for any newly diagnosed NSCLC. Despite curative R0 resection and extensive intra-operative mediastinal lymph node sampling, an elevated pre-operative CEA was associated with a significantly reduced DFS and may be a surrogate for more aggressive tumour biology. Such patients will benefit from meticulous post resection surveillance and adjuvant therapy beyond conventional TNM criteria.
PURPOSE: To assess the feasibility of a Fracture Liaison Service in Malaysia and to benchmark our service against the International Osteoporosis Foundation Best Practice Framework.
METHODS: This feasibility study was conducted at a tertiary hospital in Malaysia from March 2021 to March 2022. Patients aged ≥ 50 years admitted with fragility fractures were recruited. Excluded were those with poor prognosis or transferred out from the hospital during admission. Patients were screened, assessed, and followed up at months 4 and 12 post-fracture presentations. Data was collected using Microsoft Excel and the REDCap database. The feasibility of the Fracture Liaison Service was evaluated using the typology of feasibility.
RESULTS: A total of 140 patients (female (93/140, 66.4%), median age 77 (IQR 72, 83), hip fractures (100/140, 65.8%)) were recruited into the Fracture Liaison Service. The recruitment rate was (140/215, 65.1%), as some patients were "missed" due to the COVID-19 pandemic. The completion rate was high (101/114, 88.6%). Among those indicated for antiosteoporosis medication, 82/100 (82%) were initiated on treatment. Various "Best Practice Standards," such as patient evaluation (140/140, 100%), fall prevention (130/140, 92.9%), and medication review standards (15/15, 100%) were high. Complicated referral pathways, inexperienced staff, lack of resources, and communication issues were some of the barriers identified while implementing the Fracture Liaison Service. Challenges were overcome by modifying the service workflow and coordinating with different departments.
CONCLUSION: The Fracture Liaison Service was found to be feasible in Malaysia. It demonstrated promise in improving bone health management; however, several changes were needed to adapt the service to suit our environment.
METHODS: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level.
FINDINGS: In 2021, we estimated 4·71 million (95% UI 4·23-5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00-1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000-372 000] and 57 200 attributable deaths [34 100-80 300] in 1990, to 550 000 associated deaths [500 000-600 000] and 130 000 attributable deaths [113 000-146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000-834 000) in 1990, to 1·03 million associated deaths (909 000-1·16 million) in 2021, and from 127 000 attributable deaths (82 100-171 000) in 1990, to 216 000 (168 000-264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56-2·26) deaths attributable to AMR and 8·22 million (6·85-9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2-69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5-89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (-6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8-102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08-13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths.
INTERPRETATION: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050.
FUNDING: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust.
METHODS AND RESULTS: We analyzed the gene expression patterns on 238 fresh-frozen samples, comparing tumors with their normal adjacent tissues (NATs). HNSCC samples showed higher PCAT-1 and FSCN-1 expression compared to NATs (p
METHODS AND ANALYSIS: This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.
ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the University Malaya Medical Centre (202213-10884). Findings will be disseminated through conference presentations and peer review publications.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (www.
CLINICALTRIAL: gov); NCT05286619.
METHODS: A randomized controlled trial was conducted on 122 subjects divided into three groups: group A (40 patients with PFS) underwent manual physiotherapy, group B (42 patients with PFS) without any intervention and group C (40 healthy subjects) were matched by age, gender and BMI with each patient in group A and B. The following outcomes were evaluated at baseline and one-month of follow-ups: morphology of PF and thicknesses of CFP and KFP, pain, foot functional limitation.
RESULTS: PF thickness was significantly thickened in group A and B compared to group C (P
METHODS: A cross-sectional study was conducted online using Google Forms™. Sociodemographic as well as work and workplace data were collected. The Job Demand Inventory, Physicians' Lack of Professional Autonomy, and Health Professions Stress Inventory questionnaires were used to assess the job demand score, job autonomy score, and the level of work-related stress, respectively. Multiple linear regression was performed to determine the significant factors associated with higher work-related stress.
RESULTS: A total of 301 PCDs participated in this study with the majority being female (76.1%), Malay (67.8%), married (73.1%), medical officers (68.8%), and worked in urban (70.4%) and public primary care clinics (83%). The mean (SD) score for work-related stress was 62.8 (18.4), (score range 0-120). PCDs who had any degree of worry about being alienated by friends and relatives because of close contact with COVID-19 patients had higher work-related stress levels compared to PCDs who did not have any worry [rarely (b = 10.23, 95% CI:5.57, 14.89), sometimes (b = 10.41, 95% CI:5.68, 15.13), often (b = 10.12, 95% CI:4.16, 16.08), and always (b = 14.65, 95% CI:7.43, 21.89)]. The other significant factor was higher job demand scores (b = 1.13, 95% CI:0.91, 1.35). In contrast, PCDs who always received support from supervisors at their workplace were found to have lower work-related stress levels compared to those who did not receive any support (b=-5.65, 95% CI:-10.38, -0.93).
CONCLUSIONS: The level of work-related stress among Malaysian PCDs during the COVID-19 pandemic was higher compared to American PCDs and Malaysian physicians before the pandemic but lower compared to Australian emergency physicians during the pandemic. Urgent measures to address the above-mentioned associated factors should be implemented as another pandemic may be just around the corner.