INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Objectives: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP). Methods: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation. Results: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients’ fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate. Conclusions The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.

INTRODUCTION: Healthcare workers (HCWs) are a critical resource in the effort to control the COVID-19 pandemic. They are also a sentinel surveillance population whose clinical status reflects the effectiveness of the hospital's infection prevention measures in the pandemic. METHODS: This was a retrospective cohort study conducted in Singapore General Hospital (SGH), a 1,822-bed tertiary hospital. Participants were all HCWs working in SGH during the study period. HCW protection measures included clinical workflows and personal protective equipment developed and adapted to minimise the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. HCW monitoring comprised staff contact logs in high-risk locations, twice-daily temperature monitoring, assessment of HCWs with acute respiratory illnesses (ARIs) in the staff clinic and, in the event of an exposure, extensive contact tracing, detailed risk assessment and risk-based interventions. HCW surveillance utilised monitoring data and ARI presentations and outcomes. RESULTS: In the ten-week period between 6 January 2020 and 16 March 2020, 333 (17.1%) of 1,946 HCWs at risk of occupational COVID-19 presented with ARI. 32 (9.6%) screened negative for SARS-CoV-2 from throat swabs. Five other HCWs developed COVID-19 attributed to non-clinical exposures. From the nine COVID-19 exposure episodes investigated, 189 HCW contacts were identified, of whom 68 (36.2%) were placed on quarantine and remained well. CONCLUSION Early in an emerging infectious disease outbreak, close monitoring of frontline HCWs is essential in ascertaining the effectiveness of infection prevention measures. HCWs are at risk of community disease acquisition and should be monitored and managed to prevent onward transmission.
Humans ; COVID-19/epidemiology* ; Pandemics/prevention & control* ; SARS-CoV-2 ; Infectious Disease Transmission, Patient-to-Professional/prevention & control* ; Sentinel Surveillance ; Retrospective Studies ; Infection Control ; Health Personnel

Background: Obstructive fibrinous pseudomembrane tracheitis (OFPT) is a rare complication of endotracheal intubation. Case: We describe the case of a 73-year-old woman who underwent short-term intubation for video-assisted thoracoscopic surgery and developed an acute life-threatening stridor two days after extubation. The patient required an emergency tracheostomy to maintain airway patency and a microscopic direct laryngoscopy procedure was performed thereafter with removal of the obstructive pseudomembrane. Subsequently, the patient also suffered a non-ST-elevation myocardial infarction. The patient successfully recovered, and the tracheostomy was subsequently decannulated two months later. Histological examination revealed mucosal ulcerations and inflammatory changes. Conclusions OFPT is an uncommon cause of life-threatening airway obstruction after extubation that is not often recognized immediately but can usually be treated with early bronchoscopic intervention or microscopic direct laryngoscopy.

Background: Tuberculous disease of spine (spinal TB) is under-recognized in tuberculous (TB) meningitis.The objective of the study was to evaluate the frequency, clinical and neuroimaging changes, andoutcome in the patients with spinal TB. Methods: All the patients with spinal TB admitted in the twolargest tertiary hospitals in Kuala Lumpur from 2009 to 2017 were recruited, the clinical features weredocumented, the magnetic resonance imaging (MRI) of the spine was performed. Clinical outcome wasassessed with Modified Rankin scale (MRS). Results: Twenty two patients were recruited. This wasout of 70 TB meningitis patients (31.4%) seen over the same period. Eighteen (81.8%) patients hadconcomitant TB meningitis. The clinical features consisted of systemic symptoms with fever (63.6%),meningitis symptoms with altered sensorium (45.5%), myelopathy with paraparesis (36.4%). Thefindings on spinal MRI were discitis (36.4%), spinal meningeal enhancement (31.8%), spinal cordcompression (31.8%), psoas abscess (27.3%), osteomyelitis (22.7%), and cord oedema (22.7%). Allexcept two patients (90.9%) had involvement in psoas muscle, bone or leptomeningeal enhancement,features that can be used to differentiate from myelopathy that affect the parenchyma only, such asdemyelination. Unusual manifestations were syringomyelia and paradoxical manifestations seen in 3patients each. The outcome were overall poor, with 68% having MRS 3 or more.Conclusion: Spinal TB is common in TB meningitis. The outcome is overall poor. A heightenedawareness is crucial to enable early diagnosis and treatment.

Lipuma equates continuous sedation until death (CSD) to physician-assisted suicide/euthanasia (PAS/E) based on the premise that iatrogenic unconsciousness negates social function and, thus, personhood, leaving a patient effectively 'dead'. Others have extrapolated upon this position further, to suggest that any use of sedation and/or opioids at the end of life would be analogous to CSD and thus tantamount to PAS/E. These posits sit diametrically opposite to standard end-of-life care practices. This paper will refute Lipuma's position and the posits borne from it. We first show that prevailing end-of-life care guidelines require proportional and monitored use of sedatives and/or opioids to attenuate fears that the use of such treatment could hasten death. These guidelines also classify CSD as a last resort treatment, employed only when symptoms prove intractable, and not amenable to all standard treatment options. Furthermore, CSD is applied only when deemed appropriate by a multidisciplinary palliative medicine team. We also show that empirical data based on local views of personhood will discount concerns that iatrogenic unconsciousness is tantamount to a loss of personhood and death.
Analgesics, Opioid ; therapeutic use ; Attitude of Health Personnel ; Death ; Deep Sedation ; ethics ; Ethics, Medical ; Euthanasia ; ethics ; legislation & jurisprudence ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Palliative Care ; ethics ; Personhood ; Philosophy, Medical ; Practice Guidelines as Topic ; Suicide, Assisted ; ethics ; legislation & jurisprudence ; Terminal Care ; ethics ; Unconsciousness

INTRODUCTIONDiuretics are the mainstay of therapy for restoring the euvolaemic state in patients with decompensated heart failure. However, diuretic resistance remains a challenge.

METHODSWe conducted a retrospective cohort study to examine the efficacy and safety of ultrafiltration (UF) in 44 hospitalised patients who had decompensated heart failure and diuretic resistance between October 2011 and July 2013.

RESULTSAmong the 44 patients, 18 received UF (i.e. UF group), while 26 received diuretics (i.e. standard care group). After 48 hours, the UF group achieved lower urine output (1,355 mL vs. 3,815 mL, p = 0.0003), greater fluid loss (5,058 mL vs. 1,915 mL, p < 0.0001) and greater weight loss (5.0 kg vs. 1.0 kg, p < 0.0001) than the standard care group. The UF group also had a shorter duration of hospitalisation (5.0 days vs. 9.5 days, p = 0.0010). There were no differences in the incidence of 30-day emergency department visits and rehospitalisations for heart failure between the two groups. At 90 days, the UF group had fewer emergency department visits (0.2 vs. 0.8, p = 0.0500) and fewer rehospitalisations for heart failure (0.3 vs. 1.0, p = 0.0442). Reduction in EQ-5D™ scores was greater in the UF group, both at discharge (2.7 vs. 1.4, p = 0.0283) and 30 days (2.5 vs. 0.3, p = 0.0033). No adverse events were reported with UF.

CONCLUSIONUF is an effective and safe treatment that can improve the health outcomes of Asian patients with decompensated heart failure and diuretic resistance.

Aged ; Diuretics ; therapeutic use ; Drug Resistance ; Emergency Service, Hospital ; Female ; Heart Failure ; therapy ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Readmission ; Retrospective Studies ; Treatment Outcome ; Ultrafiltration

BACKGROUNDDepression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity (SC) in depression and compared the prescriptions of antidepressants in depressed patients with and without SC.

METHODSA total of 2320 patients treated with antidepressants in 8 Asian countries were examined, and a diagnosis was based on the International Classification of Disease, 10 th revision. We listed 17 common chronic somatic diseases. Patients' socio-demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure.

RESULTSOf the patients examined, 1240 were diagnosed with depression and 30% of them (n = 375) had SC. The most common comorbid condition was diabetes (23.7%). The patients with SC were more likely to seek help at a general hospital (74.7% vs. 47.2%), and had a higher incidence of symptoms involving sadness, disturbed sleep, and poor appetite. Noradrenergic and specific serotonergic antidepressant was prescribed more for patients with SC than for those without SC (30.4% vs. 22.9%).

CONCLUSIONSSC is common in depressed Asian patients. It is important to strengthen the recognition of depression, especially in general hospitals and when patients report some somatic discomfort. It is also a matter of urgency to establish evidence-based guidelines for the use of new antidepressants in depressed patients with SC.

Adult ; Antidepressive Agents ; therapeutic use ; Asia ; Asian Continental Ancestry Group ; Depression ; drug therapy ; epidemiology ; Drug Prescriptions ; statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Prevalence

Background: Ribosomal proteins are traditionally associated with protein biosynthesis until recent studies that implicated their extraribosomal functions in human diseases and cancers. Our previous studies using GeneFishingTM DEG method and microarray revealed underexpression of three ribosomal protein genes, RPS26, RPS27, and RPL32 in cancer of the nasopharynx. Herein, we investigated the expression pattern and nucleotide sequence integrity of these genes in nasopharyngeal carcinoma to further delineate their involvement in tumourigenesis. The relationship of expression level with clinicopathologic factors was also statistically studied. Methods: Quantitative Polymerase Chain Reaction was performed on nasopharyngeal carcinoma and their paired normal tissues. Expression and sequence of these three genes were analysed. Results: All three ribosomal protein genes showed no significant difference in transcript expressions and no association could be established with clinicopathologic factors studied. No nucleotide aberrancy was detected in the coding regions of these genes. Conclusion: There is no early evidence to substantiate possible involvement of RPS26, RPS27, and RPL32 genes in NPC tumourigenesis.