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Purpose: To determine percentage of patients with sub-therapeutic beta-lactam exposure in our intensive care units (ICU) and to correlate target attainment with clinical outcomes., Materials and Methods: Multi-centre, prospective, observational study was conducted in ICUs from three hospitals in Singapore from July 2016 to May 2018. Adult patients (≥21 years) receiving meropenem or piperacillin-tazobactam were included. Four blood samples were obtained during a dosing interval to measure and determine attainment of therapeutic targets: unbound beta-lactam concentration above (i) minimum inhibitory concentration (MIC) at 40% (meropenem) or 50% (piperacillin) of dosing interval (40-50%fT > MIC) and (ii) 5 × MIC at 100% of dosing interval (100%fT > 5 × MIC). Correlation to clinical outcomes was evaluated using Cox regression., Results: Beta-lactam levels were highly variable among 61 patients, with trough meropenem and piperacillin levels at 21.5 ± 16.8 mg/L and 101.6 ± 81.1 mg/L respectively. Among 85 sets of blood samples, current dosing practices were able to achieve 94% success for 40-50%fT > MIC and 44% for 100%fT > 5 × MIC. Failure to achieve 40-50%fT > MIC within 48 h was significantly associated with all-cause mortality (HR: 9.0, 95% CI: 1.8-45.0), after adjustment for APACHE II score. Achievement of 100%fT > 5 × MIC within 48 h was significantly associated with shorter length of hospital stay., Conclusion: Current dosing practices may be suboptimal for ICU patients. Beta-lactam TDM may be useful., Competing Interests: Declaration of Competing Interest All authors have disclosed that they do not have any conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Mindfulness practices may have a role in reducing suffering and improving spiritual well-being among patients with serious illness. The efficacy, feasibility and acceptability of such interventions warrant further exploration in the palliative care population., Objective: To investigate the effect of a brief mindfulness practice, the 5-minute mindfulness of peace intervention, on suffering and spiritual well-being among palliative care patients., Methods: A randomized controlled study was conducted on adult palliative care patients with moderate to severe levels of suffering. Participants in the intervention arm were guided through a 5-minute mindfulness of peace exercise while participants in the control arm received 5 minutes of active listening. Pre- and post-intervention suffering and spiritual well-being were measured using the Suffering Pictogram and the FACIT-Sp-12 questionnaire, respectively., Results: 40 participants completed the study. 5-minute mindfulness of peace significantly reduced suffering (median = -3.00, IQR = 2.00) more than 5 minutes of active listening (median = -1.00, IQR = 1.75), U = 73.50, z = -3.48, p = 0.001, η 2 = 0.31. FACIT-Sp-12 score also significantly improved in the intervention arm (median = +5.00, IQR = 2.75) compared with the control arm after 5 minutes (median = +1.00, IQR = 3.00), U = 95.50, z = -2.85, p = 0.004, η 2 = 0.21., Conclusions: A brief 5-minute mindfulness of peace exercise is effective in providing immediate relief of suffering and improving spiritual well-being. It is a useful and feasible intervention among patients receiving palliative care for rapidly and momentarily reducing spiritual suffering.

Background: The risk of environmental contamination by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the intensive care unit (ICU) is unclear. We evaluated the extent of environmental contamination in the ICU and correlated this with patient and disease factors, including the impact of different ventilatory modalities., Methods: In this observational study, surface environmental samples collected from ICU patient rooms and common areas were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Select samples from the common area were tested by cell culture. Clinical data were collected and correlated to the presence of environmental contamination. Results were compared to historical data from a previous study in general wards., Results: In total, 200 samples from 20 patient rooms and 75 samples from common areas and the staff pantry were tested. The results showed that 14 rooms had at least 1 site contaminated, with an overall contamination rate of 14% (28 of 200 samples). Environmental contamination was not associated with day of illness, ventilatory mode, aerosol-generating procedures, or viral load. The frequency of environmental contamination was lower in the ICU than in general ward rooms. Eight samples from the common area were positive, though all were negative on cell culture., Conclusion: Environmental contamination in the ICU was lower than in the general wards. The use of mechanical ventilation or high-flow nasal oxygen was not associated with greater surface contamination, supporting their use and safety from an infection control perspective. Transmission risk via environmental surfaces in the ICUs is likely to be low. Nonetheless, infection control practices should be strictly reinforced, and transmission risk via droplet or airborne spread remains.

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24-6.47) and neutrophil count (aOR 2.39, 95% CI 1.34-4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828-0.979). Median APACHE II score was 19 (IQR 17-22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89-129). Median peak FiO2 was 0.75 (IQR 0.6-1.0), positive end-expiratory pressure 12 (IQR 10-14) and plateau pressure 22 (IQR 18-26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5-13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1-9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1-11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s 2 (IQR 1.0-1.6%/s 2 ), elevated PT median Min2 5.2%/s 2 (3.6-5.7%/s 2 ), elevated aPTT median Max2 (clot deceleration) 1.3%/s 2 (IQR 0.8-1.4%/s 2 ) elevated PT median Max2 3.8%/s 2 (IQR 2.6-4.2%/s 2 ), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2-91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 μg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

Background: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients., Method and Results: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16)., Conclusions: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Background: The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19., Methods: This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors., Findings: Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission., Interpretation: Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted., Funding: Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Since the outbreak of the 2019 novel coronavirus (COVID-19), the role of physiotherapy for patients with COVID-19 infection has been highlighted by various international guidelines. Despite that, clinical information regarding the rehabilitation of patients with COVID-19 infection remains limited. In this case series, we provide a novel insight into the physiotherapy management in patients infected with COVID-19 in Singapore. The main findings are: (1) Respiratory physiotherapy interventions were not indicated in the majority of the patients with COVID-19 in this case series; (2) During rehabilitation, exertional or position-related desaturation is a common feature observed in critically ill patients with COVID-19 infection locally. This clinical phenomenon of exertional or positional-related desaturation has significantly slowed down the progression of rehabilitation in our patients. As such, it can potentially result in a significant burden on healthcare resources to provide rehabilitation to these patients. Based on these findings, we have highlighted several recommendations for the provision of rehabilitation in patients who are critically ill with COVID-19., (Copyright © 2020 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

We describe the clinical, laboratory and radiological features of 3 critically ill patients with COVID-19 who developed severe encephalopathy. The first patient did not regain consciousness when sedation was removed at the end of 2 weeks of intensive care. He had received treatment with convalescent plasma. His clinical examination was remarkable for intact brainstem reflexes, roving eye movements, later transient ocular flutter; and then what appeared to be slow ocular dipping. He had no coherent volitional response to the environment. The second patient recovered with measurable cognitive deficits after a prolonged period of encephalopathy. He had received combination treatment with interferon beta 1b and lopinavir/ritonavir. The third patient remained in persistent, severe agitated delirium and died 3 months into his illness. The MRI of the 3 patients showed multifocal abnormalities predominantly in the cerebral white matter, with varying involvement of the grey matter, brainstem and spinal cord. Case 1's MRI changes were consistent with acute disseminated encephalomyelitis. The patients also displayed blood markers, to varying degree, of autoimmunity and hypercoagulability. We were not able to convincingly show, from microbiological as well as immunological evaluation, if the effects of COVID-19 on these patients' nervous system were a direct consequence of the virus, proinflammatory-thrombotic state or a combination. Patient 1 responded partially to empirical, albeit delayed, therapy with intravenous immunoglobulins. Patient 2 recovered with no specific treatment. These cases illustrate the need to understand the full spectrum of encephalopathy associated with COVID-19 so as to better guide its management., (© 2020 The Author(s).)

Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration-time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r 2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing.

Objectives: A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been observed. We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID-19 patients., Methods: Demographic, clinical and laboratory data from hospitalised COVID-19 patients from a single centre with two consecutive negative respiratory reverse transcription-polymerase chain reaction (RT-PCR) results were extracted from electronic medical records. Kaplan-Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding. Plasma levels of immune mediators were measured using Luminex multiplex microbead-based immunoassay., Results: There were 201 symptomatic patients included. Median age was 49 years (interquartile range 16-61), and 52.2% were male. Median RNA shedding was 14 days (IQR 9-18). Intermittent shedding was observed in 77 (38.3%). We did not identify any factor associated with prolonged or intermittent viral RNA shedding. Duration of shedding was inversely correlated with plasma levels of T-cell cytokines IL-1β and IL-17A at the initial phase of infection, and patients had lower levels of pro-inflammatory cytokines during intermittent shedding., Conclusions: Less active T-cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding. Intermittent shedding is common and may explain re-detection of viral RNA in recovered patients., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Background: Early formulations of Takeda's tetravalent dengue vaccine candidate (TAK-003) have demonstrated notably higher neutralizing antibody responses against serotype 2 than other serotypes. Here, we assessed the immunogenicity and tolerability in adults living in Singapore of two TAK-003 formulations: an early formulation, referred to as HD-TDV, and a new formulation with 10-fold lower serotype 2 potency, referred to as TDV (NCT02425098)., Methods: Subjects aged 21-45 years were stratified by baseline dengue serostatus and randomised 1:1 to receive a single dose of either HD-TDV or TDV. Immunogenicity was evaluated at Days 15, 30, 90, 180, and 365 post-vaccination as geometric mean titres (GMTs) of neutralising antibodies and seropositivity rates. Viremia was assessed per vaccine strain. Solicited and unsolicited adverse events (AEs) were assessed by severity and causality., Results: Of 351 subjects randomised, 176 received HD-TDV and 175 received TDV. Peak GMTs against all serotypes were observed at Day 30, with highest GMTs against DENV-2 in both groups. In subjects seronegative at baseline, the response to DENV-2 was less dominant with TDV (Day 30 GMTs: 813 for TDV, 10,966 for HD-TDV). In these subjects, DENV-4 seropositivity rates and GMTs were higher with TDV (Day 30 GMTs: 58 for TDV, 21 for HD-TDV; seropositivity rates: 76% for TDV, 60% for HD-TDV). Viremia mainly occurred for TDV-2 in both vaccine groups, with a lower incidence in TDV recipients, and mostly resolved by Day 30. Both vaccine formulations showed an acceptable safety profile with similar overall rates of solicited and unsolicited AEs across vaccine groups., Conclusions: These results suggest a more balanced immune response with the new formulation TDV compared with the early formulation HD-TDV, particularly in subjects who were seronegative prior to vaccination, and support the choice of the new formulation for the phase 3 efficacy assessment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [VT, MB, YH, MR, AB and DW are permanent employees of Takeda Vaccines. The institutions of JGL, HMO, YSL, SK, LW, JP, LML, and THL received funds from Takeda Vaccines to support the costs of the trial.]., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The multi-disciplinary antimicrobial stewardship team at the study hospital conducts prospective review and feedback on all inpatient orders of piperacillin-tazobactam and carbapenems. In addition, the team provides non-antibiotic recommendations (i.e. additional investigations and infectious disease reviews). This study aimed to describe the impact of these recommendations on patient outcomes., Methods: Patients on carbapenem and piperacillin-tazobactam who received at least one non-antibiotic recommendation between January 2012 and August 2014 were included in this study. Acceptance and rejection of non-antibiotic recommendations by the managing physician were compared. The primary outcome was 30-d mortality., Results: Non-antibiotic recommendations were made in 166 patients. There were no differences in baseline characteristics between patients for whom recommendations were accepted and patients for whom recommendations were rejected. Thirty-day mortality (18.0% vs. 34.5%, P = 0.02) was significantly lower in patients who had at least one non-antibiotic recommendation accepted. Multi-variate analysis found that Charlson's comorbidity score [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.03-1.42, P = 0.03], APACHE II score (OR 1.10, 95% CI 1.01-1.19, P < 0.01), hepatobiliary source of infection (OR 10.19, 95% CI 1.44-72.13, P = 0.02) and acceptance of at least one non-antibiotic recommendation (OR 0.39, 95% CI 0.17-0.88, P = 0.02) were independently associated with 30-d mortality., Conclusions: During prospective review and feedback of piperacillin-tazobactam and carbapenems, acceptance of non-antibiotic recommendations was found to be associated with a reduction in 30-d mortality., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Antimicrobial stewardship is used to combat antimicrobial resistance. In Singapore, a tertiary hospital has integrated a computerised decision support system, called Antibiotic Resistance Utilisation and Surveillance-Control (ARUSC), into the electronic inpatient prescribing system. ARUSC is launched either by the physician to seek guidance for an infectious disease condition or via auto-trigger when restricted antibiotics are prescribed. This paper describes the implementation of ARUSC over three phases from 1 May 2011 to 30 April 2013, compared factors between ARUSC launches via auto-trigger and for guidance, examined factors associated with acceptance of ARUSC recommendations, and assessed user acceptability. During the study period, a monthly average of 9072 antibiotic prescriptions was made, of which 2370 (26.1%) involved ARUSC launches. Launches via auto-trigger comprised 48.1% of ARUSC launches. In phase 1, 23% of ARUSC launches were completed. This rose to 38% in phase 2, then 87% in phase 3, as escapes from the ARUSC programme were sequentially disabled. Amongst completed launches for guidance, 89% of ARUSC recommendations were accepted versus 40% amongst completed launches via auto-trigger. Amongst ARUSC launches for guidance, being from a medical department [adjusted odds ratio (aOR)=1.20, 95% confidence interval (CI) 1.04-1.37] and ARUSC launch during on-call (aOR=1.81, 95% CI 1.61-2.05) were independently associated with acceptance of ARUSC recommendations. Junior physicians found ARUSC useful. Senior physicians found ARUSC reliable but admitted to having preferences for antibiotics that may conflict with ARUSC. Hospital-wide implementation of ARUSC encountered hurdles from physicians. With modifications, the completion rate improved., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objectives: To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic., Methods: Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD)., Results: The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, P<0.001), the rate of adverse drug reactions was lower [11/204 (5.4%) versus 12/96 (12.5%), P=0.037], there was less diarrhoea [9/204 (4.4%) versus 12/96 (12.5%), P=0.015], there was a lower incidence of carbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081]., Conclusions: This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Antimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes., Materials and Methods: After 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge., Results: Of 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016)., Conclusion: Our prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.

The US National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) created the Cancer Genome Atlas (TCGA) Project in 2006. The TCGA's goal was to sequence the genomes of 10,000 tumors to identify common genetic changes among different types of tumors for developing genetic-based treatments. TCGA offered great potential for cancer patients, but in reality has little impact on clinical applications. Recent reports place the past TCGA approach of testing a small tumor mass at a single time-point at a crossroads. This crossroads presents us with the conundrum of whether we should sequence more tumors or obtain multiple biopsies from each individual tumor at different time points. Sequencing more tumors with the past TCGA approach of single time-point sampling can neither capture the heterogeneity between different parts of the same tumor nor catch the heterogeneity that occurs as a function of time, error rates, and random drift. Obtaining multiple biopsies from each individual tumor presents multiple logistical and financial challenges. Here, we review current literature and rethink the utility and application of the TCGA approach. We discuss that the TCGA-led catalogue may provide insights into studying the functional significance of oncogenic genes in reference to non-cancer genetic background. Different methods to enhance identifying cancer targets, such as single cell technology, real time imaging of cancer cells with a biological global positioning system, and cross-referencing big data sets, are offered as ways to address sampling discrepancies in the face of tumor heterogeneity. We predict that TCGA landmarks may prove far more useful for cancer prevention than for cancer diagnosis and treatment when considering the effect of non-cancer genes and the normal genetic background on tumor microenvironment. Cancer prevention can be better realized once we understand how therapy affects the genetic makeup of cancer over time in a clinical setting. This may help create novel therapies for gene mutations that arise during a tumor's evolution from the selection pressure of treatment.

Fast and accurate risk stratification is essential in the emergency department (ED) as it allows clinicians to identify chest pain patients who are at high risk of cardiac complications and require intensive monitoring and early intervention. In this paper, we present a novel intelligent scoring system using heart rate variability, 12-lead electrocardiogram (ECG), and vital signs where a hybrid sampling-based ensemble learning strategy is proposed to handle data imbalance. The experiments were conducted on a dataset consisting of 564 chest pain patients recruited at the ED of a tertiary hospital. The proposed ensemble-based scoring system was compared with established scoring methods such as the modified early warning score and the thrombolysis in myocardial infarction score, and showed its effectiveness in predicting acute cardiac complications within 72 h in terms of the receiver operation characteristic analysis.

Study Design: A case report of staphylococcal transverse myelitis., Objectives: To illustrate the clinical presentation of acute transverse myelitis due to Staphylococcus aureus, without a contiguous source of infection., Setting: National Neuroscience Institute., Case Report: A 79-year-old female was diagnosed with acute transverse myelitis. Clues to an infectious etiology included fever, raised inflammatory markers and cerebrospinal fluid neutrophilic pleocytosis. Staphylococcal etiology was established based on cerebrospinal fluid and blood cultures. Despite extensive investigations, no contiguous or systemic source of infection could be identified. She was treated with appropriate antibiotics; however, neurological recovery was poor., Conclusions: Bacterial myelitis may occur in isolation and the diagnosis should not be discounted when evaluation shows an absence of a contiguous or systemic source of infection.

The objective of this study was to measure the related parameters of intercarotid artery (ICA) in the operative plane of endonasal transsphenoidal approach for hypophyseal surgeries. Nine parameters of the ICA were examined in the computed tomographic angiographic (CTA) scan of 101 patients. The shortest distance between the middle point of the nasal columella and the projective point of the ICA (D(3)) was 85.50 (5.79) mm. The shortest distance between the anterior wall of the sphenoid sinus and the projective point of the ICA (D(4)) was 16.93 (3.50) mm. The distance between the bilateral projective points of the ICA (D(5)) was 21.60 (3.45) mm. The shortest distance from the anterior wall of the sphenoid sinus to the line between the bilateral projective points of the ICA (D(6)) was 12.1 (3.91) mm. The shortest distance between the middle point of nasal columella and the anterior wall of the sphenoid sinus (D(7)) was 72.67 (5.99) mm. The width of the angle between the bilateral ICA projective point from the middle point of the nasal columella (A(1)) was 14.9 (2.32) degrees. The width of the angle between the bilateral ICA projective points from the anterior-most point of sphenoid sinus (A(2)) was 85.49 (18.12) degrees. Clinically, it is relatively safe to work within the distances and angles measured in this research, and these results may provide information for clinical surgery of pituitary tumor.

Introduction: Otorrhoea is a common complaint in Ear, Nose and Throat clinics. This study aimed to establish the pathogens involved in cases of otorrhoea in Singapore, their sensitivity patterns and the effectiveness of empirical management., Methods: A retrospective chart review was conducted on 91 patients with otorrhoea who had undergone swab cultures between July 2010 and February 2011., Results: Of the 91 cases, 53% were diagnosed empirically as bacterial otitis externa and 25% as otomycosis. Aerobic bacteria accounted for 35.8% of the microorganisms cultured, while 34.7% were fungi and 29.5% were anaerobic bacteria. Pseudomonas (P.) aeruginosa and Staphylococcus (S.) aureus made up 31.6% and 21.0% of the microorganisms, respectively. 20% of S. aureus grown was methicillin-resistant. Aspergillus was the most common fungus and 19% of cultures were polymicrobial. 38% of patients had their treatment changed on the basis of culture results, as no improvement was observed on follow-up. P. aeruginosa was sensitive to ciprofloxacin and gentamicin in 81.8% and 76.0% of patients, respectively, while S. aureus was sensitive to cloxacillin in 93.8% and clindamycin in 87.5% of patients., Conclusion: The common microorganisms involved in otorrhoea in Singapore are P. aeruginosa, Aspergillus and S. aureus. Resistant strains of Pseudomonas spp. are now present. Methicillin-resistant S. aureus is increasingly prevalent and highly sensitive to vancomycin. Aminoglycoside and fluoroquinolone-containing eardrops are suitable first-line topical antimicrobials. Cloxacillin may be started should a concomitant oral antimicrobial be warranted empirically or for S. aureus infections. Otomycosis should be considered in patients who show no improvement with antibiotics.

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology--survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments.

Background: Pandemic influenza (H1N1) 2009 is susceptible to oseltamivir. There are few reports on its clinical and virologic response to oseltamivir., Methods: During the pandemic containment response in Singapore, all patients with positive polymerase chain reaction (PCR) results for pandemic influenza (H1N1) 2009 were hospitalized, given oseltamivir for 5 days, and discharged when daily PCR results for combined nasal and throat swab samples became negative. Six patients had concurrent positive viral culture and PCR results., Results: The median age of the first 70 consecutive patients was 26 years (interquartile range, 21-38 years); 60% were men, and 29% had comorbidity. The mean time (+/-SD) from illness onset to hospital admission was 3+/-2 days. Influenza-like illness was noted in 63% of patients. Fever occurred in 91%, cough in 88%, sore throat in 66%, and rhinorrhea in 53% of patients. The mean duration (+/-SD) of viral shedding from illness onset was day 6+/-2 days. Viral shedding persisted beyond 7 days in 37% of patients. Clinical features and viral shedding were similar between those with and without comorbidity, except the former had more cough and lower oxygen saturation. Patients receiving oseltamivir on days 1 to 3 of illness had significantly shorter viral shedding duration, compared with those treated from day 4 onwards (P < .05). The mean durations (+/-SD) of positive PCR and viral culture results were 5+/-8 and 4+/-18 days, respectively, for 6 patients with concurrent positive viral culture and PCR results., Conclusions: Prolonged viral shedding was noted in young immunocompetent adults with mild pandemic influenza (H1N1) 2009 despite receipt of oseltamivir. When prescribed during the first 3 days of illness, oseltamivir shortened the duration of viral shedding.

Suspected nosocomial Aspergillus fumigatus infections in an Australian hematology unit were investigated by molecular typing of clinical and environmental isolates using polymerase chain reaction fingerprinting, CSP typing, and multilocus microsatellite typing. Only multilocus microsatellite typing revealed that all isolates were genetically distinct. The selection of an appropriate typing method is essential for effective outbreak investigations.

Dengue virus is estimated to cause over 100 million infections throughout the world annually. While dengue infections can have a wide range of infections, atypical manifestations have been described. These involve the central nervous system, cardiac alterations and hepatitis. Here, we highlight a case of dengue haemorrhagic fever (DHF) with fulminant hepatitis. A 55-year-old male was admitted for 16 days, developing severe thrombocytopenia as low as 6x10(9)/L, haematocrit of 48% with transaminitis: ALT: 3,515 U/L, AST: 12,541 U/L, GGT: 1,094 U/L. Subsequent investigations excluded any occult liver lesions, hepatitis A, B and C, Wilson's disease, Epstein-Barr virus and Cytomegalo virus as possible causes. His dengue PCR was positive. His condition subsequently improved with supportive treatment. Liver injury from dengue virus is mediated by its direct infection of hepatocytes and kupffer cells. While mild to moderate elevations of serum aminotransferases (ALT and AST<5X normal) are common in dengue virus infection, liver failure rarely dominate the clinical picture. Liver dysfunction was commoner in DHF, with case reports indicating that severe hepatic dysfunction (ALT and AST>10X normal) was seen with DHF associated with spontaneous bleeding tendencies. Overall prognosis depends on age and other concomitant co-morbidities. We seek to review the literature on dengue infections with hepatitis and discuss issues pertaining to pathophysiology of liver impairment in dengue, the frequency of transaminitis associated with DHF and the overall prognosis.

The purpose of this study was to investigate knowledge, perceptions of tuberculosis (TB) and intent to receive chest X-ray screening among indigenous (Taiwanese of ethnic Malayo-Polynesian descent) nursing students in Taiwan. A convenience sample was chosen from an technical institute in northern Taiwan that maintained admission quotas and provided scholarships for indigenous students. This school had over 150 classes and around 7,000 students, about 20% -25% of whom were ethnically indigenous. A power analysis based on a pilot study showed that a large effect size required a minimum sample of 485. To attain this number, 50 classes from years one through five were randomly selected based on an expected sampling of 20 students per classroom. In all, 1,000 questionnaires were distributed and 865 returned, for a response rate of 86.5%. A cross-sectional study design was used, and this study was run between the months of February and June 2003. Survey responses were self-reported in two questionnaires that gathered information on respondent knowledge and perceptions regarding TB and intent to take chest X-ray tests. Study results showed a moderate level of general knowledge about TB, misunderstandings regarding transmission vectors, and low perceptions regarding susceptibility. The knowledge score was associated with perceived benefits and barriers to preventing TB. Different places of residence influenced perceived barriers to preventing and treating TB. Age was negatively associated with the perceived benefits of receiving a chest X-ray exam for TB. Indigenous nursing students with higher perceptions of susceptibility and severity and lower perception of barriers on preventing TB had a higher level of intent to take the X-ray exam. Nursing schools must address the subject of TB in-depth and design age-specific curricula that incorporate multifaceted strategies for different students. Additionally, health educators should design health education programs targeted to dispel misconceptions and improve both knowledge and levels of awareness of tuberculosis among the indigenous population in order to enhance their willingness and ability to detect TB.

Previous studies have indicated that excitatory amino acids are involved in many afferent pathways. This study investigated the effects of intravenous MK-801 [an N-methyl-D-aspartate (NMDA) receptor-associated channel blocker] on several well-known respiratory reflexes elicited by afferent stimulation of the superior laryngeal (SLN), the intercostal (ICN), and the phrenic (PN) nerves. Control responses to stimulation were obtained from recordings of phrenic nerve activity in decerebrate, paralyzed cats. Inspiratory termination elicited by the delivery of stimulus trains to either the SLN or the ICN persisted after MK-801. The onset latency or duration of the short-latency excitations produced by SLN or ICN stimulation were unchanged. The transient inhibitions produced by SLN, ICN, PN, or medullary stimulation showed no significant changes in threshold, onset latency, or duration. Withholding lung inflation produced apneusis after administration of MK-801, indicating a central effect of the drug. Higher doses of MK-801 did not alter the parameters of these reflexes. These data indicate that NMDA-dependent neurotransmission is not required for the production of these reflexes.

This study investigated a possible role of the rostral dorsolateral pons (including nucleus parabrachialis medialis and Kölliker-Fuse nucleus) in mediating several inspiratory inhibitions. These inhibitions included the transient inhibition of phrenic inspiratory motor output produced by stimulation of the superior laryngeal nerve (SLN), the intercostal nerve (ICN) or the phrenic nerve (PN), as well as the inspiratory termination produced by trains of stimuli delivered to the SLN or ICN. In decerebrate, paralyzed, and artificially ventilated cats, the inhibitions produced by stimulation of these nerves were observed before and after lesioning (either radiofrequency, n = 8, or electrolytic, n = 9) the dorsolateral pons. Delivery of stimulus trains to the SLN or the ICN continued to elicit inspiratory termination following pontine lesions with no significant change in the threshold. There were no significant effects of bilateral dorsolateral pontine lesions on the threshold, onset latency, or duration of the short-latency, transient inhibitions produced by SLN, ICN or PN stimulation. From these data, we conclude that the rostral dorsolateral pons is not required in the production of any of these inhibitory reflexes.