Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M‐CaP) Study to investigate the ...clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi‐ethnic Asian men at real‐world setting. The M‐CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow‐up and vital status data were retrieved prospectively from the hospital‐based patients’ case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression‐free survival (bPFS). The median age at diagnosis of M‐CaP patients was 70 years (interquartile range, IQR 65–75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow‐up for all patients was 23.5 months (IQR 15.9–33.6). Although 58.1% presented with late‐stage cancer, we observed ethnic and geographic disparities in late‐stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6–20.8), respectively. Late stage at presentation remains a challenge in multi‐ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer.
Late stage at presentation remains a challenge in multi‐ethnic Asian men. We observed ethnic and geographic disparities in late stage prostate cancer diagnosis. Early detection is imperative to improve treatment outcome and survival of prostate cancer patients.
The J‐CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate‐specific antigen, Gleason score, and clinical TNM ...staging. Here, we aimed to assess the generalisability of this tool in multi‐ethnic Asians. Performance of J‐CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M‐CaP) and Japan Study Group of Prostate Cancer (J‐CaP) databases, respectively. Using the original J‐CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate‐risk disease in the M‐CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0–8 scale in the modified J‐CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J‐CAPRA score threshold was adjusted for intermediate (modified J‐CAPRA score 3–5) and high‐risk (modified J‐CAPRA score ≥6) groups in M1 patients. Using J‐CaP database, validation analysis showed that overall survival, prostate cancer‐specific survival, and progression‐free survival of modified intermediate and high‐risk groups were comparable to those of original J‐CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M‐CaP database were reclassified into high‐risk category. Modified J‐CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging.
The modified J‐CAPRA scoring system is a risk assessment tool to predict the outcome of primary androgen deprivation therapy (ADT) based on Gleason score, prostate‐specific antigen, and clinical M stage alone. It is beneficial and applicable in stratifying the risk and predicting the treatment outcomes of M1 patients without T and/or N staging.
To report clinical features and treatment outcomes of ocular juvenile xanthogranuloma (JXG).
Retrospective case series.
There were 32 tumors in 31 eyes of 30 patients with ocular JXG.
Review of ...medical records.
Tumor control, intraocular pressure (IOP), and visual acuity.
The mean patient age at presentation was 51 months (median, 15 months; range, 1-443 months). Eye redness (12/30, 40%) and hyphema (4/30, 13%) were the most common presenting symptoms. Cutaneous JXG was concurrently present in 3 patients (3/30, 10%), and spinal JXG was present in 1 patient (1/30, 3%). The ocular tissue affected by JXG included the iris (21/31, 68%), conjunctiva (6/31, 19%), eyelid (2/31, 6%), choroid (2/31, 6%), and orbit (1/31, 3%). Those with iris JXG presented at a median age of 13 months compared with 30 months for those with conjunctival JXG. In the iris JXG group, mean IOP was 19 mmHg (median, 18 mmHg; range, 11-30 mmHg) and hyphema was noted in 8 eyes (8/21, 38%). The iris tumor was nodular (16/21, 76%) or diffuse (5/21, 24%). Fine-needle aspiration biopsy was used in 10 cases and confirmed JXG cytologically in all cases. The iris lesion was treated with topical (18/21, 86%) and/or periocular (4/21, 19%) corticosteroids. The eyelid, conjunctiva, and orbital JXG were treated with excisional biopsy in 5 patients (5/9, 56%), topical corticosteroids in 2 patients (2/9, 22%), and observation in 2 patients (2/9, 22%). Of 28 patients with a mean follow-up of 15 months (median, 6 months; range, 1-68 months), tumor regression was achieved in all cases, without recurrence. Two patients were lost to follow-up. Upon follow-up of the iris JXG group, visual acuity was stable or improved (18/19 patients, 95%) and IOP was controlled long-term without medication (14/21 patients, 74%). No eyes were managed with enucleation.
Ocular JXG preferentially affects the iris and is often isolated without cutaneous involvement. Iris JXG responds to topical or periocular corticosteroids, often with stabilization or improvement of vision and IOP.
Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed ...co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19.
The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded.
We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives.
In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist.
National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.
The potential applications of nanomaterials in therapeutics are immense and to fully explore this potential, it is important to understand the interaction of nanoparticles with cellular components. ...To examine the interaction between nanoparticles and cell membrane receptors, this report describes the use of advanced fluorescence techniques to measure interactions between hydroxyapatite (HA) nanoparticles and epidermal growth factor receptors (EGFRs), as a model system. FITC‐labelled HA nanoparticles and monomeric red fluorescent protein (mRFP)‐conjugated EGFRs expressed in Chinese hamster ovary cells (CHO‐K1) were generated and their interaction measured using acceptor photobleaching‐fluorescence resonance energy transfer (AP‐FRET) and fluorescence lifetime imaging microscopy‐fluorescence resonance energy transfer (FLIM‐FRET). Results confirmed that hydroxyapatite nanoparticles not only interacted with EGFR but also attenuated downstream EGFR signalling, possibly by hindering normal dimerization of EGFR. Furthermore, the extent of signal attenuation suggested correlation with specific surface area of the nanoparticles, whereby greater specific surface area resulted in greater downstream signal attenuation. This novel demonstration establishes fluorescence techniques as a viable method to study nanoparticle interactions with proteins such as cell surface receptors. The approach described herein can be extended to study interactions between any fluorescently labelled nanoparticle‐biomolecule pair.
Current knowledge of the interaction between engineered nanoparticles and cell surface receptors is limited. Using fluorescent techniques, hydroxyapatite nanoparticles are found to interact with epidermal growth factor receptors and attenuate downstream signaling. Fluorescent techniques could be exploited for novel cell‐nanoparticle interaction studies and for the development of nanotherapeutics.
Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an ...important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease.
This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations.
Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33).
NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity.
National Institute for Health Research and Medical Research Council.
Health-related quality of life instruments tend to include a great many items. This imposes a burden on the respondents as well as undermining response rate and data quality. In this study we ...developed a shortened version of the Functional Living Index-Cancer (FLIC), now called Quick-FLIC, and examined its measurement properties. A questionnaire package, self-administered by 140 patients, included the FLIC and the Functional Assessment of Cancer Therapy-General. A factor analysis and clinical judgement were used to shorten the FLIC, which included 22 items. Each subscale of FLIC was shortened to include two or three items only. The Quick-FLIC included a total of only 11 items. Nevertheless, the measurement properties of the Quick-FLIC and its subscales were comparable to those of the original FLIC. It is concluded that the shortening of established health-related quality of life instruments is viable in oncology research.
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