Measurement of renal congestion and compliance following intravenous fluid administration using shear wave elastography.

Objective: Ultrasound shear wave elastography (SWE) is a novel technique that may provide non-invasive measurements of renal compliance. We aimed to investigate the relationship between intravenous (IV) fluid administration and change in SWE measurements. We hypothesised that following IV fluid administration in healthy volunteers, global kidney stiffness would increase and that this increase in stiffness could be quantified using SWE. Our second hypothesis was that graduated doses of IV fluids would result in a dose-dependent increase in global kidney stiffness measured by SWE. Design: Randomised prospective study. Setting: Intensive Care Unit. Participants: Healthy volunteers aged 18-40 years. Interventions: Participants were randomised to receive 20 ml/kg, 30 ml/kg, or 40 ml/kg of normal saline. The volume of fluid infused was based on the actual body weight recorded. Main outcome measures: We recorded average SWE stiffness (kPa with standard deviation of the mean), median SWE stiffness (kPa), and the interquartile range. Results: Ninety-eight percent of participants (44/45) demonstrated an increase in global kidney stiffness following administration of IV fluids. The average SWE pre fluid administration was 7.572 kPa ± 2.38 versus 14.9 kPa ± 4.81 post fluid administration (p < 0.001). In subgroup analysis, there were significant changes in global kidney stiffness pre and post fluid administration with each volume (ml/kg) of fluid administered. Average percentage change in global kidney stiffness from baseline was compared between the three groups. There was no significant difference when comparing groups 1 and 2 (197.1% increase ± 49.5 vs 216.1% ± 72.0, p » 0.398), groups 2 and 3 (216.1% increase ± 72.0 vs 197.8% ± 59.9, p » 0.455), or groups 1 and 3 (197.1% increase ± 49.5 vs 197.8% ± 59.9, p » 0.972). Conclusions: Fluid administration results in immediately visible and quantifiable changes in global kidney stiffness across all infused volumes of fluid.

Serum creatinine to absolute lymphocyte count ratio effectively risk stratifies patients who require intensive care in hospitalized patients with coronavirus disease 2019.

Patients with preexisting kidney disease or acute kidney injury had poorer outcomes in coronavirus disease 2019 (COVID-19) illness. Lymphopenia was associated with more severe illness. Risk stratification with simple laboratory tests may help appropriate site patients in a cost-effective manner and ease the burden on healthcare systems. We examined a ratio of serum creatinine level to absolute lymphocyte count at presentation (creatinine-lymphocyte ratio, CLR) in predicting outcomes in hospitalized patients with COVID-19. We analyzed 553 consecutive polymerase chain reaction-positive SARS-COV-2 hospitalized patients. Patients with end-stage kidney disease were excluded. Serum creatinine and full blood count (FBC) examination were obtained within the first day of admission. We examined the utility of CLR in predicting adverse clinical outcomes (requiring intensive care, mechanical ventilation, acute kidney injury requiring renal replacement therapy or death). An optimized cutoff of CLR > 77 was derived for predicting adverse outcomes (72.2% sensitivity, and 83.9% specificity). Ninety-seven patients (17.5%) fell within this cut off. These patients were older and more likely to have chronic medical conditions. A higher proportion of these patients had adverse outcomes (13.4% vs 1.1%, P < .001). On receiver operating curve analyses, CLR predicted patients who had adverse outcomes well (area under curve [AUC] = 0.82, 95%CI 0.72-0.92), which was comparable to other laboratory tests like serum ferritin, C-reactive protein and lactate dehydrogenase. Elevated CLR on admission, which may be determined by relatively simple laboratory tests, was able to reasonably discriminate patients who had experienced adverse outcomes during their hospital stay. This may be a simple and cost-effective means of risk stratification and triage.

Haematological profile of COVID-19 patients from a centre in Singapore.

BACKGROUND: Haematological markers such as absolute lymphopenia have been associated with severe COVID-19 infection. However, in the literature to date, the cohorts described have typically included patients who were moderate to severely unwell with pneumonia and who required intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 admitted to a single centre in Singapore. METHODS: We examined 554 consecutive PCR positive SARS-COV-2 patients admitted to a single tertiary healthcare institution from Feb 2020 to April 2020. In all patients a full blood count was obtained within 24 h of presentation. RESULTS: Patients with pneumonia had higher neutrophil percentages (66.5 ± 11.6 vs 55.2 ± 12.6%, p < 0.001), lower absolute lymphocyte count (1.5 ± 1.1 vs 1.9 ± 2.1 x109/L, p < 0.011) and absolute eosinophil count (0.2 ± 0.9 vs 0.7 ± 1.8 × 109/L, p = 0.002). Platelet counts (210 ± 56 vs 230 ± 61, p = 0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories. CONCLUSION: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.

Utility of conventional clinical risk scores in a low-risk COVID-19 cohort.

BACKGROUND: Several specific risk scores for Coronavirus disease 2019 (COVID-19) involving clinical and biochemical parameters have been developed from higher-risk patients, in addition to validating well-established pneumonia risk scores. We compared multiple risk scores in predicting more severe disease in a cohort of young patients with few comorbid illnesses. Accurately predicting the progression of COVID-19 may guide triage and therapy. METHODS: We retrospectively examined 554 hospitalised COVID-19 patients in Singapore. The CURB-65 score, Pneumonia Severity Index (PSI), ISARIC 4C prognostic score (4C), CHA2DS2-VASc score, COVID-GRAM Critical Illness risk score (COVID-GRAM), Veterans Health Administration COVID-19 index for COVID-19 Mortality (VACO), and the "rule-of-6" score were compared for three performance characteristics: the need for supplemental oxygen, intensive care admission and mechanical ventilation. RESULTS: A majority of patients were young (≤ 40 years, n = 372, 67.1%). 57 (10.3%) developed pneumonia, with 16 (2.9% of study population) requiring supplemental oxygen. 19 patients (3.4%) required intensive care and 2 patients (0.5%) died. The clinical risk scores predicted patients who required supplemental oxygenation and intensive care well. Adding the presence of fever to the CHA2DS2-VASc score and 4C score improved the ability to predict patients who required supplemental oxygen (c-statistic 0.81, 95% CI 0.68-0.94; and 0.84, 95% CI 0.75-0.94 respectively). CONCLUSION: Simple scores including well established pneumonia risk scores can help predict progression of COVID-19. Adding the presence of fever as a parameter to the CHA2DS2-VASc or the 4C score improved the performance of these scores in a young population with few comorbidities.

Elevated liver enzymes in hospitalized patients with COVID-19 in Singapore.

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.

Hemisensory syndrome: Hyperacute symptom onset and age differentiates ischemic stroke from other aetiologies.

BACKGROUND: An important cause of hemisensory syndrome is ischemic stroke. However, the diagnostic yield of neuroradiological imaging on hemisensory syndrome is low. Therefore, we aim to describe patients hospitalized with isolated hemisensory syndrome, and to identify clinical features associated with an aetiology of ischemic stroke. METHODS: We performed a single centre retrospective observation study, identifying patients who were hospitalised with hemisensory syndrome from October 2015 to March 2016, and whom underwent a magnetic resonance imaging (MRI) brain during the admission. Ischemic stroke was defined as the presence of restricted diffusion-weighted image on the MRI brain. Clinical information was analysed and compared between patients with and without stroke seen on MRI brain. RESULTS: 79 patients, 36 (45.6%) males and 43 (54.4%) females, aged between 30 to 87 years (mean 54), were included in the final analysis. 18 (22.8%) patients were identified to have an acute ischemic stroke. Clinical features associated with ischemic stroke in hospitalised patients with hemisensory syndrome include symptom onset of ≤24 h at presentation (odds ratio 31.4, 95% CI 3.89-254.4), advanced age (odds ratio 1.14, CI 1.05-1.25) and smoking (odds ratio 7.35, 95% CI 1.20-45). CONCLUSION: Older patients, with a history of smoking, and who present with an acute onset of symptoms, are more likely to have ischemic stroke as the cause of their hemisensory syndrome.

COVID-19 associated parotitis.

While Coronavirus 2019 (COVID-19) typically presents with respiratory tract symptoms, atypical manifestations have been reported. We present a case of a 46-year-old man who presented with fever but no respiratory tract symptoms, and later develops bilateral parotitis. We review the literature for all other reported cases of parotitis and describe common features of these cases. It is important to consider COVID-19 in cases of parotitis, as this impacts patient management and ensures important infection control measures are undertaken.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

INTRODUCTION: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing. METHODS: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR. RESULTS: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain. CONCLUSION: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.

Management of acute pyelonephritis in the emergency department observation unit.

INTRODUCTION: This study aimed to assess the effectiveness of the emergency department observation unit (EDOU) for patients with acute pyelonephritis in a Singapore tertiary academic medical centre. METHODS: We reviewed the clinical records of consecutive patients who presented with pyelonephritis between 1 July 2012 and 31 October 2014 to collect information on demographics, symptoms, signs, laboratory and radiological results, treatment, and clinical outcomes. RESULTS: Of 459 emergency department (ED) patients who were identified as having pyelonephritis, 164 (35.7%) were managed in the EDOU. Successful management in the EDOU was achieved in 100 (61.0%) patients. Escherichia coli was the predominant (64.6%) micro-organism in urine cultures and was positive in 106 patients. Patients diagnosed with acute pyelonephritis who were successfully managed in the EDOU had a lower incidence of nausea (32.0% vs. 60.9%, p < 0.001) and vomiting (15.0% vs. 50.0%, p < 0.001) compared to those who were not successful. CONCLUSION: EDOU is useful for both observation and treatment of patients with acute pyelonephritis. Urine cultures are sufficient for the identification of the culprit micro-organism. Patients who present with prominent symptoms of vomiting should have routine administration of antiemetics, while consideration for second-line antiemetics is recommended for those with persistent symptoms.

Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.

OBJECTIVES: The vast majority of COVID-19 cases in Singapore have occurred amongst migrant workers. This paper examined trends in the hospitalised cases and tested the assumption that the low severity of disease was related to the relatively young affected population. METHODS: All patients with PCR-positive SARS-CoV-2 admitted from February to April 2020 were divided into: (i) imported cases, (ii) locally-transmitted cases outside migrant worker dormitories and (iii) migrant worker dormitory cases. They were examined for underlying comorbidities, clinical progress and outcomes. RESULTS: Imported cases (n = 29) peaked in mid-March 2020, followed by local cases (n = 100) in mid-April 2020; migrant worker cases (n = 425) continued to increase in late April 2020. Migrant worker cases were younger, had few medical comorbidities and less severe disease. As the migrant worker cases increased, the proportion of patients with pneumonia decreased, whilst patients presenting earlier in their illness and asymptomatic disease became more common. CONCLUSION: Singapore experienced a substantial shift in the population at risk of severe COVID-19. Successful control in the community protected an aging population. Large migrant worker dormitory outbreaks occurred, but the disease incurred was less severe, resulting in Singapore having one of the lowest case fatality rates in the world.

Jonsen's Four Topics Approach as a Framework for Clinical Ethics Consultation.

This was an in-depth qualitative study that looked at the reasons patients were referred to the Clinical Ethics Committee (CEC) of an acute hospital in Singapore and explore how the CEC approached cases referred. Jonsen's four topics approach was applied in the deliberative process for all cases. A comprehensive review of the case records of 28 patients referred consecutively to the CEC from 1 January 2012 to 31 December 2014 was conducted. Data and information was collated from the referral forms, patient medical records, and emails communicated among CEC members. A deductive approach to thematic analysis based on Jonsen's four topics approach was used to analyze the documents. Majority of the patients were male (94%), Chinese (76%), and above 65 years of age (41%). Ethical dilemmas surfaced due to differences in opinion regarding withholding of aggressive management (53%), withdrawing treatment (35%), and ascertaining patient's autonomy (12%). In most cases, the patients' preference on end-of-life care was unknown (82%). The main reasons for referral to the CEC were conflicts in clinical management and uncertainty about the decision-making capacity of patients. The CEC members tended to emphasize on "patient preference" more than the other quadrants in the four topics approach as they worked through each case. The Jonsen's four topics approach lays the groundwork to frame ethical dilemmas that can be easily applied in the clinical setting and is a useful tool for the CEC's teaching and discussion. Nonetheless, the approach only organizes ethical dilemmas and requires clinicians to apply own judgment in weighing ethical principles. Further studies can look into adapting the four topics approach to suit the local practices and context.

Screening for Frailty and Sarcopenia Among Older Persons in Medical Outpatient Clinics and its Associations With Healthcare Burden.

OBJECTIVES: With an aging population and increase in multimorbidity, the importance of screening for frailty and sarcopenia has become a public health priority. Several tools to do so exist. This study aimed to examine whether the SARC-F and Edmonton frail screening tools are useful in clinical practice to identify at-risk patients for negative health outcomes who would benefit from intervention. DESIGN: This is a cross-sectional study of patients attending medical specialist outpatient clinics at the National University Hospital, Singapore from May 2015 to February 2016. MEASUREMENTS: Frailty and sarcopenia were identified using the Edmonton Frail Scale and SARC-F questionnaires, respectively. Other clinically relevant data including basic demographics, presence of caregiver, number of follow-ups, medications and hospital readmissions in the past 1 year, Charlson comorbidity index, and modified Barthel index were collected from chart review. RESULTS: A total of 115 patients 65 years old and older were screened. Of the sample, 44.3% (n = 51) of patients were sarcopenic, whereas 27.0% (n = 31) were classified as frail; 23.5% (n = 27) were both frail and sarcopenic; and 87.1% of frail patients were sarcopenic, whereas 47.1% of sarcopenic patients were frail. Sarcopenia and frailty were associated with a higher Charlson comorbidity index, higher likelihood of requiring a caregiver, more medical specialty follow-ups, polypharmacy, more than 2 hospital admissions within a year, a higher number of falls and falls with serious consequences. This affected their perceived health status with 50.0% of robust patients rating their health excellent compared with 19.6% of sarcopenic patients (P < .001), 9.7% of frail patients (P < .001) and sarcopenic and frail patients scoring the lowest with 3.7% (P < .001). CONCLUSIONS: The prevalence of frailty and sarcopenia among older adults attending medical outpatient clinic is high. Both syndromes are predictors of recurrent hospital admissions, polypharmacy, multiple medical clinic appointments, higher rate of falls, and falls with serious consequences. Early identification of older adults at risk of adverse health outcomes would aid in instituting timely intervention to reduce healthcare burden and improve quality of life.

Factors associated with prolonged length of stay in older patients.

INTRODUCTION: Prolonged stay in acute hospitals increases the risk of hospital-acquired infections in older patients, and disrupts patient flow and access to care due to bed shortages. We aimed to investigate the factors associated with prolonged length of stay (pLOS) among older patients (aged ≥ 78 years) in a tertiary hospital, to identify the potentially modifiable risk factors that could direct interventions to reduce length of stay (LOS). METHODS: During a three-month period from January 2013 to March 2013, we identified 72 patients with pLOS (LOS ≥ 21 days) and compared their demographic and clinical variables with that of 281 randomly selected control patients (LOS < 21 days) using univariate and multivariate logistic regression analyses. RESULTS: The mean age of the patients was 85.30 ± 5.34 years; 54% of them were female and 72% were of Chinese ethnicity. Logistic regression revealed the following significant factors for increased LOS: discharge to intermediate and long-term care services (odds ratio [OR] 9.22, 95% confidence interval [CI] 3.56-23.89; p < 0.001); increased severity of illness (OR 2.41, 95% CI 1.12-5.21; p = 0.025); and presence of caregiver stress (OR 3.85, 95% CI 1.67-8.91; p = 0.002). CONCLUSION: Presence of caregiver stress and nursing home placement are potential modifiable risk factors of pLOS among older patients. Early identification and management of caregiver stress, as well as expediting discharge planning, may help to reduce the length of stay for this cohort.