Evaluation of a novel direct RT-LAMP assay for the detection of SARS-CoV-2 from saliva samples in asymptomatic individuals.

Large scale screening of health care workers and the general population for asymptomatic COVID-19 infection requires modalities that are amenable to testing at scale while retaining acceptable levels of sensitivity and specificity. This study evaluated a novel COVID-19 Direct-RT LAMP assay using saliva samples in asymptomatic individuals by comparison to RT-PCR. Additional studies were performed using VTM collected from routine diagnostic testing. Analytical sensitivity was determined for Direct RT-LAMP assay using the WHO International Standard. Finally, quantified results from RT-PCR testing of 9177 nose and throat swabs obtained from routine diagnostic testing were used to estimate the sensitivity of Direct RT-LAMP using the limit of detection curve obtained from the analytical sensitivity data. Results from saliva testing demonstrated a sensitivity of 40.91% and a specificity of 100% for Direct RT-LAMP. The sensitivity and specificity for nose and throat swabs were 44.85% and 100% respectively. The 95% limit of detection (LOD) for Direct RT-LAMP was log 7.13 IU/ml (95% 6.9-7.5). The estimated sensitivity for Direct-RT LAMP based on the results of 9117 nose and throat swabs was 34% and 45% for saliva and VTM respectively. The overall diagnostic sensitivity of Direct RT-LAMP was low compared to RT-PCR. Testing of nose and throat swabs and estimating the sensitivity based on a large cohort of clinical samples demonstrated similar results. This study highlights the importance of utilising the prospective collection of samples from the intended target population in the assessment of diagnostic sensitivity.

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

BACKGROUND: Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. METHODS: This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. DISCUSSION: When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

Paediatric Anti-Müllerian Hormone measurement: Male and female reference intervals established using the automated Beckman Coulter Access AMH assay.

OBJECTIVE: Anti-Müllerian Hormone (AMH) concentration is high at birth in males, demonstrating the presence of functional testicular tissue in the prepubertal period, and acting as a useful marker in the investigation of paediatric reproductive disorders. AMH also provides a tool in the investigation of female virilization, premature ovarian failure and polycystic ovarian syndrome in childhood. Robust, assay-specific paediatric AMH reference intervals are therefore required for clinical interpretation of results. The aim of this study was to derive age-specific AMH reference intervals for males and females aged 0-18 years. DESIGN AND PATIENTS: Plasma samples were obtained from patients at Royal Manchester Children's Hospital and analysed for AMH using the automated Beckman Coulter Access AMH Assay. Patients under investigation for paediatric reproductive or endocrine disorders were excluded from the study. MEASUREMENTS: Seven hundred and 2 patient plasma samples (465 male, 237 female) were subject to AMH measurement, and results were analysed in order to derive continuous and discrete reference intervals for the paediatric age range. RESULTS: Clear discrimination between male and female AMH results was evident in the prepubertal age range, with some overlap between the genders following pubertal onset. CONCLUSIONS: We have derived age-related reference intervals for plasma AMH in the paediatric age range (0-18 years) using the automated Beckman Coulter Access AMH assay which will aid in the investigation of paediatric endocrine disorders such as disorders of sexual development.

A Multifaceted Quality Improvement Programme to Improve Acute Kidney Injury Care and Outcomes in a Large Teaching Hospital.

Acute kidney injury (AKI) is now widely recognised as a serious health care issue, occurring in up to 25% of hospital in-patients, often with worsening of outcomes. There have been several reports of substandard care in AKI. This quality improvement (QI) programme aimed to improve AKI care and outcomes in a large teaching hospital. Areas of documented poor AKI care were identified and specific improvement activities implemented through sequential Plan-Do-Study-Act (PDSA) cycles. An electronic alert system (e-alert) for AKI was developed, a Priority Care Checklist (PCC) was tested with the aid of specialist nurses whilst targeted education activities were carried out and data on care processes and outcomes monitored. The e-alert had a sensitivity of 99% for the detection of new cases of AKI. Key aspects of the PCC saw significant improvements in their attainment: Detection of AKI within 24 hours from 53% to 100%, fluid assessment from 42% to 90%, drug review 48% to 95% and adherence to nine key aspects of care from 40% to 90%. There was a significant reduction in variability of delivered AKI care. AKI incidence reduced from 9% of all hospitalisations at baseline to 6.5% (28% reduction), AKI related length of stay reduced from 22.1 days to 17 days (23% reduction) and time to recovery (AKI days) 15.5 to 9.8 days (36% reduction). AKI related deaths also showed a trend towards reduction, from an average of 38 deaths to 34 (10.5%). The number of cases of hospital acquired AKI were reduced by 28% from 120 to 86 per month. This study demonstrates significant improvements related to a QI programme combining e-alerts, a checklist implemented by a nurse and education in improving key processes of care. This resulted in sustained improvement in key patient outcomes.

Effect of a cooked meat meal on serum creatinine and estimated glomerular filtration rate in diabetes-related kidney disease.

OBJECTIVE: Fasting is not routinely recommended for renal function tests, despite the known effects of cooked meat on creatinine. We therefore studied variation in creatinine and estimated glomerular filtration rate (eGFR) after a standardized cooked meat meal in 80 subjects: healthy volunteers and diabetic patients with chronic kidney disease (CKD) stages 1 and 2, 3a, 3b, and 4 (n = 16/group). RESEARCH DESIGN AND METHODS: The interventions were a standardized cooked meat and a nonmeat meal, each providing ∼54 g protein, together with 250 mL water, on separate days. Fasting and postprandial blood samples at 1, 2, and 4 h were drawn for creatinine measurement using a kinetic alkaline picrate assay on an Olympus AU640 analyzer. The modified four-variable Modification of Diet in Renal Disease equation traceable to isotope dilution mass spectrometry creatinine was used to calculate eGFR. RESULTS: Consumption of a standardized cooked meat meal significantly increased serum creatinine and resulted in significant fall in eGFR in all stages of CKD studied; 6 of 16 CKD 3a patients were misclassified as CKD 3b. This effect of cooked meat on serum creatinine disappears after 12 h of fasting in all study participants. CONCLUSIONS: Creatine in meat is converted to creatinine on cooking, which is absorbed, causing significant increases in serum creatinine. This could impact management, as threshold for commencing and withdrawing certain medications and expensive investigations is defined by eGFR. eGFR calculated using fasting serum creatinine would be a better reflection of kidney function in these patients.

Inferior petrosal sinus ACTH and prolactin responses to CRH in ACTH-dependent Cushing's syndrome: a single centre experience from the United Kingdom.

Inferior petrosal sinus sampling (IPSS) of ACTH with CRH stimulation helps distinguish pituitary ACTH-dependent Cushing's syndrome from the ectopic ACTH syndrome (EAS). The usefulness of the paradoxical response of other pituitary hormones including prolactin to CRH remains controversial. Data from 33 IPSS procedures carried out at the Walton Centre for Neurology and Neurosurgery in Liverpool were analyzed. Patients were selected for this procedure if they had been diagnosed with ACTH dependent Cushing's syndrome and the majority had no obvious pituitary adenoma on Magnetic Resonance Imaging. Satisfactory simultaneous bilateral catheterization was accomplished in 23/33 (success rate 70%). The diagnostic sensitivity of a basal central/peripheral ACTH ratio >2.0 and >3 post-CRH was 94%. In two patients with subsequently confirmed EAS the maximal central/peripheral ACTH ratio was <2.0 on basal samples and did not change following CRH. The maximal central/peripheral prolactin ratio was noted at 5 min post-CRH, coinciding with the maximal central/peripheral ACTH ratio. The intersinus gradient (ISG) of ACTH was paralleled by a consistent ISG of prolactin and in 7 out of 9 patients (with successful bilateral IPSS and unilateral adenomas) the ISG of prolactin correctly lateralized the microadenoma whereas the ISG of ACTH correctly lateralized in 8 out of 9 patients. Neither of the patients with EAS achieved a central/peripheral prolactin ratio >2 in the basal state and >3 post-CRH. Bilateral catheterization of inferior petrosal sinuses can be successful in up to 70% of cases. Prolactin measurements do not have superior lateralizing capability compared with ACTH but may be useful in the differential diagnosis of pituitary-driven from EAS.

Performance measurement in healthcare: part I--concepts and trends from a State of the Science Review.

OBJECTIVE: Performance measurement is touted as an important mechanism for organizational accountability in industrialized countries. This paper describes a systematic review of business and health performance measurement literature to inform a research agenda on healthcare performance measurement. METHODS: A search of the peer-reviewed business and healthcare literature for articles about organizational performance measurement yielded 1,307 abstracts. Multi-rater relevancy ratings, citation checks, expert nominations and quality ratings resulted in 664 articles for review. Key themes were extracted from the papers, followed by multi-reader validation. Information was supplemented with grey literature. RESULTS: The performance literature was diverse and fragmented, and relevant evidence was difficult to locate. Most literature is non-empirical and originates from the United States and the United Kingdom. No agreement on definitions or concepts is evident within or across disciplines. Study quality is not high in either field. Performance measurement arose in public services and business at about the same time. The evolution of thought on performance measurement ranges from unfettered enthusiasm to sober reassessment. CONCLUSIONS: The research base on performance measurement is in its infancy, and evidence to guide practice is sparse. A coherent multidisciplinary research agenda on the topic is needed.

Performance measurement in healthcare: part II--state of the science findings by stage of the performance measurement process.

OBJECTIVE: This paper summarizes findings of a comprehensive, systematic review of the peer-reviewed and grey literature on performance measurement according to each stage of the performance measurement process--conceptualization, selection and development, data collection, and reporting and use. It also outlines implications for practice. METHODS: Six hundred sixty-four articles about organizational performance measurement from the health and business literature were reviewed after systematic searches of the literature, multi-rater relevancy ratings, citation checks and expert author nominations. Key themes were extracted and summarized from the most highly rated papers for each performance measurement stage. RESULTS: Despite a virtually universal consensus on the potential benefits of performance measurement, little evidence currently exists to guide practice in healthcare. Issues in conceptualizing systems include strategic alignment and scope. There are debates on the criteria for selecting measures and on the types and quality of measures. Implementation of data collection and analysis systems is complex and costly, and challenges persist in reporting results, preventing unintended effects and putting findings for improvement into action. CONCLUSION: There is a need for further development and refinement of performance measures and measurement systems, with a particular focus on strategies to ensure that performance measurement leads to healthcare improvement.

Plasma adiponectin increases postprandially in obese, but not in lean, subjects.

OBJECTIVE: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. RESEARCH METHODS AND PROCEDURES: We studied 13 lean and 11 obese subjects after a 10-hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. RESULTS: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) microg/mL vs. 8.6 (6.5 to 11.3) microg/mL], but rose 4-fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) microg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) microg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. DISCUSSION: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.