ORCID Profile
0000-0002-2916-2818
Current Organisations
Western Health
,
University College London Medical School - Royal Free Campus
,
Royal Australasian College of Physicians
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Publisher: Elsevier BV
Date: 04-2012
Publisher: Springer Science and Business Media LLC
Date: 20-11-2021
DOI: 10.1186/S12879-021-06829-7
Abstract: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, 0.17605/OSF.IO/GEHFX ). In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92 1.02) with between-study heterogeneity not beyond chance (I 2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
Publisher: Cold Spring Harbor Laboratory
Date: 07-12-2017
DOI: 10.1101/225359
Abstract: Since the mid-1980s there have been increasing reports of severe community-acquired pyogenic liver abscess, meningitis and bloodstream infections caused by hypervirulent Klebsiella pneumoniae , predominantly encompassing clonal group (CG) 23 serotype K1 strains. Common features of CG23 include a virulence plasmid associated with iron scavenging and hypermucoidy, and a chromosomal integrative and conjugative element (ICE) encoding the siderophore yersiniabactin and the genotoxin colibactin. Here we investigate the evolutionary history and genomic ersity of CG23 based on comparative analysis of 98 genomes. Contrary to previous reports with more limited s les, we show that CG23 comprises several deep branching sublineages dating back to the 1870s, many of which are associated with distinct chromosomal insertions of ICEs encoding yersiniabactin. We find that most liver abscess isolates ( %) belong to a dominant sublineage, CG23-I, which emerged in the 1920s following acquisition of ICE Kp10 (encoding colibactin in addition to yersiniabactin) and has undergone clonal expansion and global dissemination within the human population. The unique genomic feature of CG23-I is the production of colibactin, which has been reported previously as a promoter of gut colonisation and dissemination to the liver and brain in a mouse model of CG23 K. pneumoniae infection, and has been linked to colorectal cancer. We also identify an antibiotic-resistant subclade of CG23-I associated with sexually-transmitted infections in horses dating back to the 1980s. These data show that hypervirulent CG23 K. pneumoniae was circulating in humans for decades before the liver abscess epidemic was first recognised, and has the capacity to acquire and maintain AMR plasmids. These data provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae . To further support such studies we present an open access and completely sequenced human liver abscess isolate, SGH10, which is typical of the globally disseminated CG23-I sublineage.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Elsevier BV
Date: 06-2021
Publisher: Radiological Society of North America (RSNA)
Date: 03-2016
DOI: 10.1148/RADIOL.2015150289
Abstract: To investigate the feasibility of using a modified portable isolation chamber, which conforms to Centers for Disease Control and Prevention (CDC) isolation requirements, in the imaging of infectious patients. This study was approved by the ethics committee, and all participants gave written informed consent. In this prospective study, the isolation chamber was assessed for computed tomographic (CT), magnetic resonance (MR), and positron emission tomographic (PET) image uniformity and noise by using uniform phantoms. For each modality, equivalent phantom examinations were performed without the isolation chamber. Paired analyses of the differences from these baseline values were conducted by finding the mean difference in the matched sections for each image quality parameter. A potential increase in CT patient dose was assessed, and MR radiofrequency (RF) interference was monitored. Eight participants with active pulmonary tuberculosis (mean age, 48.1 years age range, 26-88 years five men, three women) were then examined within a hybrid PET/MR imager. The 95% confidence intervals for the difference in the two matched population means were determined by using the two-sided t distribution for each of the phantom study imaging modalities. Phantom images were evaluated for image uniformity and noise. Increased image noise can affect low contrast resolution, which has the potential to mimic or mask abnormalities when the differences between healthy and diseased tissues are small clinically, CT image noise is maintained at a constant level with dose modulation. Increased attenuation of annihilation photons, when not corrected for, could lead to photopenic areas on the PET image PET image nonuniformity complied with guidelines. Artifacts on the MR image due to RF noise spikes could mask abnormalities paired analysis of variations in MR imaging mean signal-to-noise ratio and uniformity from baseline were within 5% for both gradient-echo and spin-echo sequences. In the eight participants who underwent imaging, the increased radiation dose for the attenuation of the isolation chamber would have resulted in a mean increase in patient size-specific dose estimate of 0.32 mGy ± 0.04 (standard deviation). The RF noise assessment revealed no prominent increase at any frequency band. The eight participants were examined within the isolation chamber without incident. CONCLUSION A modified portable isolation chamber, which conforms to CDC infection control guidelines, was found to be feasible within the confines of CT, MR imaging, and PET environments.
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2021-054528
Abstract: To summarise the evidence relating to the prevalence of anxiety and depression among healthcare workers (HCWs) during the COVID-19 pandemic. An umbrella review of systematic reviews was undertaken using the Joanna Briggs Institute (JBI) methods. The Cochrane database of systematic reviews, JBI Evidence Synthesis, MEDLINE, Web of Science, PsycINFO, Embase and CINAHL were searched in March 2021 for reviews published in English. Systematic reviews reporting the prevalence of anxiety and depression among HCWs during the COVID-19 pandemic. Two researchers screened each abstract and independently reviewed full text articles. Study quality was assessed using the JBI critical appraisal tool for systematic reviews, and the degree of overlap in primary studies was calculated. Ten systematic reviews (100 unique studies), including 169 157 HCWs from 35 countries were included. The prevalence of anxiety among all HCWs ranged from 22.2% (95% CI 21.3% to 23.1%) to 33.0% (95% CI 31.9% to 34.1%). The prevalence of anxiety among physicians (n=5820) was reported to be between 17% and 19.8% and for nurses (n=14 938) between 22.8% and 27%. The prevalence of depression among all HCWs ranged from 17.9% (95% CI 17.1% to 18.8%) to 36% (95% CI 34.9% to 37.1%). The prevalence of depression among physicians (n=643) and nurses (n=8063) was reported to be 40.4% and 28%, respectively. There is wide variation evident in the presence of anxiety and depression among HCWs. In particular, the prevalence of depression among physicians was high. Strategies to reduce the incidence of anxiety and depression are urgently required. CRD42021238960.
Publisher: Frontiers Media SA
Date: 07-09-2017
Publisher: JMIR Publications Inc.
Date: 27-03-2020
DOI: 10.2196/15702
Abstract: As people living with HIV infection require lifelong treatment, nonadherence to medication will reduce their chance of maintaining viral suppression and increase the risk of developing drug resistance and HIV transmission. This study aimed to evaluate the efficacy of a mobile app, Mobile Interactive Supervised Therapy (MIST), for improving adherence to oral HIV medications among HIV-infected adults in Singapore. We conducted a two-group pilot randomized controlled trial (RCT) with a process evaluation, in which 40 HIV-infected participants with once-daily medication regimes were recruited from a public tertiary hospital in Singapore and randomly assigned equally to either the intervention (receiving MIST and routine care) or control (receiving routine care only) groups. The intervention lasted for 2 months. The outcome of antiretroviral therapy (ART) adherence was measured by a 7-day recall self-report (SR), pill count (PC), an electronic medical device—Medication Event Monitoring System (MEMS)—and a mobile app—MIST (for the intervention group only). In total, 20 participants from the intervention group were interviewed at the end of the intervention to assess the acceptability of MIST. Data were collected at baseline and at 1-month and 2-month postintervention. All participants had excellent medication adherence at baseline (median 100, IQR 100-100). The use of MIST did not result in a significant improvement in ART adherence when measured by the SR, PC, and MEMS, as compared with the control group at 1-month (P values .99, .86, and .74, respectively) and 2-month (P values=.80, .84, and .82, respectively) postintervention. ART adherence also did not improve in each group over the same period. MIST was perceived to be a beneficial tool based on the process evaluation results. Although MIST did not enhance medication adherence to HIV treatments, mainly owing to the ceiling effect, it was perceived to be beneficial among the participants of this study. Our process evaluation provided useful data to further develop MIST for bigger and long-term mobile phone app–assisted intervention RCTs in the future. ClinicalTrials.gov NCT03794648 t2/show/NCT03794648
Publisher: Springer Science and Business Media LLC
Date: 07-09-2017
Publisher: JMIR Publications Inc.
Date: 27-07-2020
DOI: 10.2196/16856
Abstract: Despite the development of effective drugs for treatment, tuberculosis remains one of the leading causes of death from an infectious disease worldwide. One of the greatest challenges to tuberculosis control is patient adherence to treatment. Recent research has shown that video-based directly observed therapy is a feasible and effective approach to supporting treatment adherence in high-income settings. However, few studies have explored the potential for such a solution in a low- or middle-income country setting. Globally, these countries’ rapidly rising rate of mobile penetration suggests that the potential for translation of these results may be high. We sought to examine patient perceptions related to the use of mobile health, and specifically video-based directly observed therapy, in a previously unstudied patient demographic: patients with tuberculosis in a low-income country setting (Cambodia). We conducted a cross-sectional qualitative study in urban and periurban areas in Cambodia, consisting of 6 focus groups with tuberculosis patients who were receiving treatment (standard directly observed therapy) through a nongovernmental organization. Familiarity with mobile technology and apps was widespread in this population, and overall willingness to consider a mobile app for video-based directly observed therapy was high. However, we identified potential challenges. First, patients very much valued their frequent in-person interactions with their health care provider, which may be reduced with the video-based directly observed therapy intervention. Second, there may be technical issues to address, including how to make the app suitable for illiterate participants. While video-based directly observed therapy is a promising technology, even in country settings where mobile penetration is reportedly almost universal, it should be introduced with caution. However, the results were generally promising and yielded important insights that not only will be translated into the further adaptation of key features of video-based directly observed therapy for tuberculosis patients in Cambodia, but also can inform the future design and successful implementation of video-based directly observed therapy interventions in low- and middle-income settings more generally.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2020
DOI: 10.1186/S12879-020-05116-1
Abstract: Current tools for diagnosing latent TB infection (LTBI) detect immunological memory of past exposure but are unable to determine whether exposure is recent. We sought to identify a whole-blood transcriptome signature of recent TB exposure. We studied household contacts of TB patients healthy volunteers without recent history of TB exposure and patients with active TB. We performed whole-blood RNA sequencing (in all), an interferon gamma release assay (IGRA in contacts and healthy controls) and PET/MRI lung scans (in contacts only). We evaluated differentially-expressed genes in household contacts (log2 fold change ≥1 versus healthy controls false-discovery rate 0.05) compared these to differentially-expressed genes seen in the active TB group and assessed the association of a composite gene expression score to independent exposure/treatment/immunological variables. There were 186 differentially-expressed genes in household contacts ( n = 26, age 22–66, 46% male) compared with healthy controls ( n = 5, age 29–38, 100% male). Of these genes, 141 (76%) were also differentially expressed in active TB ( n = 14, age 27–69, 71% male). The exposure signature included genes from inflammatory response, type I interferon signalling and neutrophil-mediated immunity pathways and genes such as BATF2 and SCARF1 known to be associated with incipient TB. The composite gene-expression score was higher in IGRA-positive contacts ( P = 0.04) but not related to time from exposure, isoniazid prophylaxis, or abnormalities on PET/MRI (all P 0.19). Transcriptomics can detect TB exposure and, with further development, may be an approach of value for epidemiological research and targeting public health interventions.
Publisher: Oxford University Press (OUP)
Date: 2018
DOI: 10.1093/JTM/TAY023
Abstract: Zika and Ebola viruses can persist in semen and pose a risk for sexual transmission. To determine if dengue virus, another flavivirus, is similarly detectable in semen, we performed dengue PCR on semen in five patients with acute dengue virus infection. All five tested negative, suggesting that dengue does not pose a risk for sexual transmission.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2013
Abstract: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early ( one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. Clinical trials gov NCT01723150
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 02-2015
DOI: 10.5694/MJA14.00716
Publisher: JMIR Publications Inc.
Date: 31-07-2019
Abstract: s people living with HIV infection require lifelong treatment, nonadherence to medication will reduce their chance of maintaining viral suppression and increase the risk of developing drug resistance and HIV transmission. his study aimed to evaluate the efficacy of a mobile app, Mobile Interactive Supervised Therapy (MIST), for improving adherence to oral HIV medications among HIV-infected adults in Singapore. e conducted a two-group pilot randomized controlled trial (RCT) with a process evaluation, in which 40 HIV-infected participants with once-daily medication regimes were recruited from a public tertiary hospital in Singapore and randomly assigned equally to either the intervention (receiving MIST and routine care) or control (receiving routine care only) groups. The intervention lasted for 2 months. The outcome of antiretroviral therapy (ART) adherence was measured by a 7-day recall self-report (SR), pill count (PC), an electronic medical device—Medication Event Monitoring System (MEMS)—and a mobile app—MIST (for the intervention group only). In total, 20 participants from the intervention group were interviewed at the end of the intervention to assess the acceptability of MIST. Data were collected at baseline and at 1-month and 2-month postintervention. ll participants had excellent medication adherence at baseline (median 100, IQR 100-100). The use of MIST did not result in a significant improvement in ART adherence when measured by the SR, PC, and MEMS, as compared with the control group at 1-month ( i P /i values & .99, .86, and .74, respectively) and 2-month ( i P /i values=.80, .84, and .82, respectively) postintervention. ART adherence also did not improve in each group over the same period. MIST was perceived to be a beneficial tool based on the process evaluation results. lthough MIST did not enhance medication adherence to HIV treatments, mainly owing to the ceiling effect, it was perceived to be beneficial among the participants of this study. Our process evaluation provided useful data to further develop MIST for bigger and long-term mobile phone app–assisted intervention RCTs in the future. linicalTrials.gov NCT03794648 t2/show/NCT03794648
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/IMJ.15510
Abstract: The COVID‐19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence‐based therapies to combat disease. In particular, the use of off‐label therapies outside of a clinical trial setting has been controversial. To longitudinally study policies and prescribing practices pertaining to therapies for COVID‐19 in Australian health services during 2020. Prospective data were collected from participating Australian health services who may care for patients with COVID‐19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID‐19 policy at their service and use of therapies for COVID‐19. Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID‐19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID‐19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. Our results reflect the reactive nature of prescribing of therapies for COVID‐19 and highlight the importance of evidence‐based guidelines to assist prescribers.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2023
DOI: 10.1038/S41598-023-36530-5
Abstract: A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620–$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296–$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs. Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).
Publisher: JMIR Publications Inc.
Date: 31-10-2019
Abstract: espite the development of effective drugs for treatment, tuberculosis remains one of the leading causes of death from an infectious disease worldwide. One of the greatest challenges to tuberculosis control is patient adherence to treatment. Recent research has shown that video-based directly observed therapy is a feasible and effective approach to supporting treatment adherence in high-income settings. However, few studies have explored the potential for such a solution in a low- or middle-income country setting. Globally, these countries’ rapidly rising rate of mobile penetration suggests that the potential for translation of these results may be high. e sought to examine patient perceptions related to the use of mobile health, and specifically video-based directly observed therapy, in a previously unstudied patient demographic: patients with tuberculosis in a low-income country setting (Cambodia). e conducted a cross-sectional qualitative study in urban and periurban areas in Cambodia, consisting of 6 focus groups with tuberculosis patients who were receiving treatment (standard directly observed therapy) through a nongovernmental organization. amiliarity with mobile technology and apps was widespread in this population, and overall willingness to consider a mobile app for video-based directly observed therapy was high. However, we identified potential challenges. First, patients very much valued their frequent in-person interactions with their health care provider, which may be reduced with the video-based directly observed therapy intervention. Second, there may be technical issues to address, including how to make the app suitable for illiterate participants. hile video-based directly observed therapy is a promising technology, even in country settings where mobile penetration is reportedly almost universal, it should be introduced with caution. However, the results were generally promising and yielded important insights that not only will be translated into the further adaptation of key features of video-based directly observed therapy for tuberculosis patients in Cambodia, but also can inform the future design and successful implementation of video-based directly observed therapy interventions in low- and middle-income settings more generally.
Publisher: Oxford University Press (OUP)
Date: 23-10-2019
DOI: 10.1093/CID/CIZ881
Abstract: Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein & mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. Between November 2013 and October 2017, 152 patients (mean age, 58.7 years 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6% 2-sided 95% confidence interval, −4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. NCT01723150.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2018
DOI: 10.1038/S41467-018-05114-7
Abstract: Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICE Kp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23’s evolutionary history, showing several deep-branching sublineages associated with distinct ICE Kp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICE Kp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I’s distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K . pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K . pneumoniae . To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JINF.2010.04.004
Abstract: Guidelines recommend a proactive approach for offering vaccination to susceptible HIV-infected patients. The size of the HIV-positive population that remains susceptible to vaccine-preventable infections is largely unknown. The study determined serostatus and recalled infection and vaccination history for measles, mumps, rubella, varicella-zoster virus (VZV), hepatitis A, and hepatitis B among HIV-positive adults accessing routine care. The study recruited 200 consecutive patients with a median CD4 count of 461 (interquartile range 326, 641) cells/mm(3) 62.5% were on suppressive antiretroviral therapy. Patients underwent serological testing and completed a questionnaire about recalled infection and vaccination history. Seronegativity rates were 7.0% [95% confidence interval 3.9-11.5%] for measles, 12.0% [7.5-16.5%] for mumps, 5.0% [2.4-9.0%] for rubella, 1.5% [0.3-4.3%] for VZV, 19.5% [14.0-25.0%] for hepatitis A, and 22.5% [16.7-28.3%] for hepatitis B. For hepatitis B, seropositivity rates were 6.5% [3.5-10.9%] for surface antigen, 38.0% [31.3-44.7%] for anti-core antibody, and 33.0% [26.5-39.5%] for anti-surface antibody alone. While patients who recalled a history of infection were generally seropositive, up to 50.5% of patients were unsure of their vaccination history. A proportion of HIV-positive adults lack evidence of immunity against common, vaccine-preventable viral infections. Efforts are needed to improve knowledge and records of vaccination history.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
Publisher: Springer Science and Business Media LLC
Date: 02-01-2021
Publisher: Oxford University Press (OUP)
Date: 18-01-2013
DOI: 10.1093/CID/CIT020
Abstract: Since antibiotics were first used, each new introduced class has been followed by a global wave of emergent resistance, largely originating in Europe and North America where they were first used. Methicillin-resistant Staphylococcus aureus spread from the United Kingdom and North America across Europe and then Asia over more than a decade. Vancomycin-resistant enterococci and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae followed a similar path some 20 years later. Recently however, metallo-β-lactamases have originated in Asia. New Delhi metallo-β-lactamase-1 was found in almost every continent within a year of its emergence in India. Metallo-β-lactamase enzymes are encoded on highly transmissible plasmids that spread rapidly between bacteria, rather than relying on clonal proliferation. Global air travel may have helped facilitate rapid dissemination. As the antibiotic pipeline offers little in the short term, our most important tools against the spread of antibiotic resistant organisms are intensified infection control, surveillance, and antimicrobial stewardship.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2020
DOI: 10.1186/S13063-020-04766-5
Abstract: Primary objective: To determine the efficacy of a candidate antiviral on time to virological cure compared to standard of care within 14 days of randomisation Secondary objectives: • To determine the safety of the antiviral • To determine the clinical benefit of the antiviral over placebo according to the WHO 7-point ordinal scale • To determine the clinical benefit of the antiviral over placebo on time to resolution of clinical symptoms • To determine the effect of the antiviral over placebo on biomarkers of inflammation and immune activation This is a multi-centre, triple-blind, randomised placebo controlled phase II, 2-arm trial with parallel-group design with allocation ratio 1:1. Inclusion Criteria: • Provision of informed consent by the participant • Age ≥18 years • Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days • COVID-19 related symptom initiation within 5 days • Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. Exclusion criteria: • Known allergy to the study medication • Is on another clinical trial investigating an antiviral treatment for COVID-19 • Pregnancy • Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification • Patients with renal impairment requiring dialysis • Is deemed by the Investigator to be ineligible for any reason Participants will be recruited from, and the study visits will take place at Alfred Hospital, Monash Health, Austin Health in Victoria, Australia for hospitalised participants as well as recruitment in the community in participants homes for eligible people not requiring hospitalisation. The first candidate antiviral is favipiravir Arm 1: Favipiravir 1800 mg favipiravir BD on Day 1 followed by 800 mg BD favipiravir for the next 13 days. Arm 2: Placebo Primary outcome: Time to virological cure as defined by 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing during the 14 days after enrolment. Randomisation performed at the Alfred Hospital Clinical Trials Pharmacy using computer generated block-randomisation lists with 6 participants per block. Within each block half of the participants will be randomised to the candidate antiviral and the other half to placebo. Randomisation is stratified by study site, with participants enrolled in the community considered as a study site. Study participants, study investigators and the study statistician will be blinded to treatment allocation. The study aims to recruit 190 people (95/arm) with the first candidate antiviral favipiravir Protocol version 2.0 Dated 31-Jul-2020. Recruitment will take place between July 2020 and December 2020. clinicaltrials.gov NCT04445467 First posted 24-Jun-2020 The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2016
DOI: 10.1038/SREP29316
Abstract: Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess. First described in Asia, it is now increasingly recognized in Western countries, commonly afflicting those with Asian descent. This raises the question of genetic predisposition versus geospecific strain acquisition. We leveraged on the Antibiotics for Klebsiella Liver Abscess Syndrome Study (A-KLASS) clinical trial ongoing in ethnically erse Singapore, to prospectively examine the profiles of 70 patients together with their isolates’ genotypic and phenotypic characteristics. The majority of isolates belonged to capsule type K1, a genetically homogenous group corresponding to sequence-type 23. The remaining K2, K5, K16, K28, K57 and K63 isolates as well as two novel cps isolates were genetically heterogeneous. K1 isolates carried higher frequencies of virulence-associated genes including rmpA (regulator of mucoid phenotype A), kfu (Klebsiella ferric uptake transporter), iuc (aerobactin), iro (salmochelin) and irp (yersiniabactin) than non-K1 isolates. The Chinese in our patient cohort, mostly non-diabetic, had higher prevalence of K1 infection than the predominantly diabetic non-Chinese (Malays, Indian and Caucasian). This differential susceptibility to different capsule types among the various ethnic groups suggests patterns of transmission (e.g. environmental source, familial transmission) and/or genetic predisposition unique to each race despite being in the same geographical location.
Publisher: BMJ
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
DOI: 10.1186/S13063-020-04576-9
Abstract: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants will be recruited from hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. Participants will be randomised 1:1:1:1 to: Group 1 : standard of care Group 2 : lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form Group 3 : hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days Group 4 : lopinavir /ritonavir plus hydroxychloroquine. Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have in idual participant allocation provided through a web-based trial enrolment platform. This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required s le size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total s le size therefore is planned to be 2440. ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol.
Publisher: Public Library of Science (PLoS)
Date: 07-10-2015
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for James Molton.