Test Points Research Articles

Effect of Gender on Reaction Time in Patients Having a Psychiatric Disorder

Background: Reaction time is a measure of how fast an organism can react to a certain stimulus. As such, it is a measure of an individual’s performance and the function of sensory-motor connection. While there are studies evaluating the differences in reaction time with gender and psychiatric illness as independent variables, data are lacking when considering them together. Aims: The aim of the study is to study the gender differences in reaction time in patients suffering from psychiatric illness. Settings and Design: The study involves an observational, longitudinal comparative study in the psychiatric outpatient department (OPD) of a tertiary care facility. Materials and Methods: After institutional ethics approval, 100 patients on psychotropic medications attending psychiatry OPD were included in the study along with at least 100 relatives who were not on psychotropic medications, serving as control. Required data were collected using semi-structured pro forma. The reaction time of patients and the control group was assessed using an application on the mobile phone available online as – the “Human Benchmark test.” Data obtained were entered in the MS Excel sheet and analyzed using the computerized software and a P ≤ 0.05 was considered statistically significant. Results: In the group of patients, the males showed delayed reaction time as compared to females, while in the control group, males performed better than the female population in reaction time tests. The highest reaction time was found to be in the substance use disorder group of patients at all points of testing, followed by that of patients with schizophrenia. Conclusions: Gender did not significantly affect the reaction time in both patient and control groups.

Update to: Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore

BackgroundThis trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial.MethodsThe key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics.DiscussionThe findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter.Trial registrationClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023.

Accuracy of the 6-Minute Walk Test for Assessing Functional Capacity in Patients With Heart Failure With Preserved Ejection Fraction and Other Chronic Cardiac Pathologies: Results of the ExIC-FEp Trial and a Meta-Analysis

BackgroundHeart diseases, particularly heart failure, significantly impact patient quality of life and mortality rates. Functional capacity assessment is vital for predicting prognosis and risk in these patients. While the cardiopulmonary exercise test is considered the gold standard, the 6-minute walk test has emerged as a more accessible alternative. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity in cardiac pathologies, including heart failure with preserved ejection fraction, are unclear. The study aimed to analyse the diagnostic accuracy of the 6-minute walk test for detecting reduced functional capacity, defined as VO2max < 14 ml/kg/min, compared with the cardiopulmonary exercise test in participants with heart failure with preserved ejection fraction using data from the “Ejercicio en Insuficiencia Cardiaca con Fracción de Eyección Preservada” (ExIC-FEp) trial; and to compare these results with previous studies investigating the screening accuracy for assessing functional capacity of the 6-minute walk test in participants with other chronic cardiac pathologies through a meta-analysis.ResultsThe ExIC-FEp trial involved 22 participants with heart failure with preserved ejection fraction, who were not treated with beta-blockers, using the cardiopulmonary exercise test, specifically VO2max, as the reference test. The 6-minute walk test had a sensitivity of 70%, a specificity of 80%, and an area under the curve of 76% in the ExIC-FEp trial. Five studies were included in the meta-analysis showing a sensitivity of 79%, a specificity of 78%, and an area under the curve of 85%.ConclusionIn conclusion, the 6-minute walk test holds promise as a screening tool for assessing functional capacity in heart failure with preserved ejection fraction and chronic heart diseases, with a VO2max < 14 ml/kg/min as a reference point. It demonstrates moderate to good screening accuracy. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity, regardless of aetiology, are unclear.Trial RegistrationNCT05726474. Registered 16 February 2023, https://clinicaltrials.gov/study/NCT05726474.

Optimisation of calibration parameters for a discrete element method (DEM) model of plant-origin grains with a low elasticity modulus

This paper presents the application of the Discrete Element Method (DEM) to describe the physical properties of plant-origin grains with a low elasticity modulus for the needs of numerical simulation of processing processes. The study proposes the modelling of maize grains based on 3D scanning of real grains and further use of the multi-sphere method to fill the numerical model with a conglomerate of elementary spheres. The main aim of the paper is to develop a calibration method based on exploring parameter spaces at points selected using Sobol's grids. As criteria and functional limitations for the calibration, the following were proposed: the slope angle of repose (AoR), the radius of the heaped cone's vertex (Rad), the number of grains, and the slope height. The study results show that for the calibration of the DEM model describing maize grains, test points with a set of the following nine parameters should be used: Poisson's Ratio for grain, Density of grain, Shear Modulus, Coefficient of Restitution for grain-grain, Coefficient of Restitution for grain-material, Coefficient of static friction for grain- grain, Coefficient of static friction for grain-material, Coefficient of rolling friction for grain-grain, and Coefficient of rolling friction for grain-material.

Calibration and validation of a modified non-equilibrium boiling model for transcritical flashing flow in two-phase R744 nozzles

A modified homogeneous non-equilibrium boiling approach (HNB) was proposed for high-fidelity modelling of the trans-critical flashing process in two-phase R744 ejector nozzles. In the modified approach, the method of determining the metastable liquid saturation pressure was improved by integrating the metastable liquid enthalpy. Experimental tests were conducted on two different nozzles to calibrate the lumped accommodation coefficient in the modified HNB. The calibration dataset consisted of 30 trans-critical test points, with the motive inlet pressure ranging from 7.5 MPa to 11.5 MPa and temperature varying from 21 °C to 45 °C. It was demonstrated that the boiling coefficient was strongly related to nozzle inlet pressure and specific enthalpy. The coefficient was therefore fitted as a function of the operating condition. The modified HNB with the fitted function was then validated against another set of test data composed of 29 test points. The results demonstrated that the relative errors of the nozzle mass-flow rates were within 3 %. Finally, the modified HNB with the improved metastable liquid saturation pressure was compared and discussed with the existing HNB approach in the literature.

THE ASSESSMENT OF THE CONCRETE STRUCTURE STADIUM "SJEVERNI LOGOR" IN MOSTAR

&amp;lt;p&amp;gt;The paper presents the assessment of the stadium &amp;quot;Sjeverni logor&amp;quot; in Mostar, through the necessary steps in diagnosing the state of the existing structure: collection of existing documentation, inspection of the structure, testing and analysis, and assessment and decision on further action. Drawings of the stadium were made with defined damage and test points with non-destructive methods.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;Destruction and classification mechanisms are performed according to EN1504. The non-destructive methods used during the examination are the rebound hammer and ultrasonic pulse velocity. At the end of this paper, the results and assessment of the condition are given, and the appropriate methods of sanctions are proposed, in accordance with EN1504.&amp;lt;/p&amp;gt;

Nanopore Identification of L-, D-Lactic Acids, D-Glucose and Gluconic Acid in the Serum of Human and Animals.

DL-Lactic acid and D-glucose are important human health indicators. Their aberrant levels in body fluids may indicate a variety of human pathological conditions, suggesting an urgent need of daily monitoring. However, simultaneous and rapid analysis of DL-lactic acid and D-glucose using a sole but simple sensing system has never been reported. Here, an engineered Mycobacterium smegmatis porin A (MspA) nanopore is used to simultaneously identify DL-lactic acid and D-glucose. Highly distinguishable nanopore event features are reported. Assisted with a custom machine learning algorithm, direct identification of DL-lactic acid and D-glucose is performed with human serum, demonstrating its sensing reliability against complex and heterogeneous samples. This sensing strategy is further applied in the analysis of different animal serum samples, according to which gluconicacid is further identified. The serum samples from different animals report distinguishable levels of DL-lactic acid, D-glucose and gluconicacid, suggesting its potential applications in agricultural science and breeding industry. This sensing strategy is generally direct, rapid, economic and requires only ≈µL of input serum, suitable for point of care testing (POCT) applications.

The safety effect of increased pedestrian protection, autonomous emergency braking for pedestrians and bicyclists on passenger cars, and speed management

This was the first retrospective study to estimate the effect of increased pedestrian protection, autonomous emergency braking, and speed management to reduce serious injuries among pedestrians and bicyclists. More specifically, the aim was to estimate the injury mitigating effects of the following interventions: AEB with pedestrian and bicyclist detection, Euro NCAP pedestrian test score, active bonnet, traffic calming at pedestrian and bicycle crossings, and additionally, the combined effect of the above-mentioned treatments. The main source of data was the Swedish traffic data acquisition system (Strada), where information of road traffic crashes between passenger cars and pedestrians or bicyclists for the period 1 January 2003–31 December 2022 was obtained. Cars with optional fitment of AEB systems were identified, and the license registration number was used to access individual car equipment lists to identify whether the vehicle was equipped with AEB with pedestrian and/or cyclist detection. Information about traffic calming at pedestrian and bicycle crossings was obtained from the Swedish Transport Administration. The injury metric used was risk of permanent medical impairment (RPMI) of at least one percent and ten percent. RPMI captures the risk of long-term medical impairment based on a diagnosed injury location and Abbreviated Injury Severity (AIS) score. The relative difference between the mean values of RPMI (mRPMI1%+ and mRPMI10%+) was calculated and tested using an independent two sample t-test which was conducted for unequal sample sizes and variance. Although many results were found to be statistically non-significant, the following results were found to be significant at least at 90% level. Pedestrian mRPMI10%+ was reduced by 44% in speed zones ≤ 50 km/h comparing the group struck by cars equipped with AEB with pedestrian detection compared to the group struck by cars without the system. For cyclists, the mRPMI10%+ was reduced by 35% in speed zones ≤ 50 km/h. For crashes within ± 20 meters from a pedestrian or bicycle crossing, the AEB system reduced 60% of pedestrians mRPMI10%+ at crossings with good safety standard compared to crossings of poor safety standard. The comparison of cars with poor performance (1–9 points) in the NCAP pedestrian test and cars with a high score (28–36 points) showed that pedestrian mRPMI10%+ was reduced by 48% across all speed limits, and by 64% including only those aged ≤ 64 years. For bicyclists, a significant reduction of cyclist mRPMI10%+ was found comparing low scoring cars to high scoring cars in ≤ 30 km/h speed limit (-73%) and across all speed limits (-36%). Including only those aged ≤ 64 years, the reduction was 49%. For the active bonnet, a significant reduction of mRPMI1%+ by 24% was observed but given that the rate of helmet wearing was higher in the group struck by cars with active bonnet, this difference cannot be attributed to an effect of an active bonnet. The STA safety rating of pedestrian and bicycle crossings showed that overall pedestrian mRPMI1%+ was reduced by 15%, while cyclists mRPMI10%+ was reduced by 32% comparing crossings of high safety level to crossings of poor safety level. The analysis of combined interventions showed that the total reduction of pedestrians and cyclists mRPMI10%+ together was 69%, from 6.4% to 2%. This paper demonstrates that a road environment with adapted infrastructure and speed, combined with passenger car technologies that improve the safety for vulnerable road users, can create significant reductions of serious (long-term) injuries among pedestrians and bicyclists.

Gradient speech change during intervention for school-aged children and adults with cleft palate ± lip

ABSTRACT Gradient speech change, where speech sound production develops in a broadly step-wise fashion towards the standard adult form, is a well-recognised phenomenon in children developing typical speech, but is much less studied in speakers with developmental speech sound disorders. Instrumental techniques, such as electropalatography (EPG), may be useful for identifying gradient speech change and may supplement phonetic transcription in important ways. This study investigated whether gradient speech change occurred in six participants with cleft palate ± lip undergoing intervention within a usage-based phonology framework (2/6 participants with speech distortions; 4/6 with pattern-based speech substitutions; combined total of 25 speech sounds targeted for intervention). Participants received weekly therapy in a hospital setting and were aged 10–27 years. Gradient speech change with target speech sounds was examined using EPG analysis, which was undertaken after every fifth session of therapy. The presence of gradient change was determined by visually examining EPG palatograms and EPG indices for target speech sounds across successive EPG test points. This study found gradient speech change occurred in 22/25 target sounds over the course of intervention. This gradient change occurred for both speech distortions and pattern-based speech substitutions. The remaining 3/25 target sounds showed categorical change. Usage-based phonology was suggested as a theory with potential for explaining gradient speech change, with both typical and atypical speech, and with speech distortions and pattern-based speech substitutions. This finding adds to other research showing that the objective data provided by instrumental techniques, such as EPG, may be a valuable complement to phonetic transcription.

Mapping decision-making pathways: Determination of intervention entry points for diagnostic tests in suspected serious infection

Background PROTECT (Platform Randomised evaluation of clinical Outcomes using novel TEChnologies to optimise antimicrobial Therapy) has brought together a team of researchers to design a platform trial to rapidly evaluate and adopt into care multiple diagnostic technologies, bringing immediate benefit to patients. Rapid diagnostic tests will be used to identify patients at risk of deterioration from severe infection, before they become critically unwell. The platform will assess their comparative clinical and cost-effectiveness relative to current standard of care. Preliminary work, conducted under a Health Technology Assessment Application Acceleration Award, provided key evidence to optimise the design of the PROTECT platform. Methods Qualitative methods which involved consulting key stakeholders in the field of serious infection addressed the key priorities. A high-level care pathway analysis focusing on serious infection in secondary care, captured the points of contact, actions, decisions, and potential outcomes associated with a patient’s care. Results Two use cases of rapid diagnostic tests for serious infection were identified; (1) in acute emergency medicine to decide on antimicrobial initiation and/or escalation of care, and (2) in hospitalised patients to monitor treatment response. Within the emergency department, clinicians believed a test would be used as an adjunct to existing standard of care and would be used to either rule-in or rule-out serious infection. The “ideal” test should be rapid, point-of-care, cheap to procure, have capacity for high usability, and ability to be performed and interpreted by all staff. Facilitators to the adoption of infection diagnostic tests is their clinical need, and the main potential barrier is poor change management and behavioural change. Conclusions Any new test should provide robust evidence of its effectiveness and have the potential to benefit the clinical pathway for patients, clinicians, and hospitals as a whole, to be considered for adoption as a new standard of care.

Correlation Glucose, Uric Acid, and Cholesterol Levels Towards Health Conditions in the Highlands: POCT Approach

Degenerative diseases arise when age increases due to the weakening of the body's physiological condition. The purpose of this study was to measure glucose, uric acid, and cholesterol levels in residents of Segunung Village to improve lifestyles and quality of life. As many as 110 residents of Segunung Village were used as subjects in this cross-sectional study. Glucose, uric acid, and cholesterol levels were measured using Point of Care Testing (POCT). A cut-off value of &lt;200 was used to define high cholesterol levels. Only cholesterol levels showed an increase when compared with reference values, while glucose and uric acid levels were normal. Interestingly glucose was significantly correlated with age (r=0.309, p=0.001). The approach using POCT describes the overall condition of Segunung villagers and can be used as a basis for glucose, uric acid, and cholesterol screening tests.

Fentanyl Test Strips for Harm Reduction: A Scoping Review.

High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.

Point of care HIV testing in dental settings in high-income countries: A mixed-methods systematic review.

Expanding HIV testing beyond specialized services has been a key strategic approach to eliminating the transmission of HIV. In recent years, dental settings have been identified as offering an opportunity for delivering point of care HIV testing (POCT) interventions. Intervention components and implementation strategies have varied across studies and there is uncertainty about the prevalence of undiagnosed HIV in the dental patient population. Therefore, this systematic review aimed to synthesize the HIV testing outcomes of intervention studies, identify the core components of POCT interventions implemented in dental settings; and understand the barriers and facilitators to intervention implementation. A mixed-methods systematic review was undertaken. Two authors reviewed abstracts and full papers for inclusion and appraised the studies using the Mixed Methods Appraisal Tool. A convergent integrated mixed methods study design underpinned the synthesis. Outcomes were presented using descriptive statistics. Intervention components were mapped to the Template for Intervention Description and Replication (TIDieR) checklist. Barriers and facilitators were described using a narrative thematic analysis. POCT was offered to 22 146 dental patients, 62.5% accepted POCT. Intervention studies that reported higher uptake of testing utilized a dedicated dental or researcher staff member to provide testing, integrated testing and provided results within the routine dental appointment and adopted a provider-initiated universal approach to offering testing. Six themes emerged that were pertinent to the barriers and facilitators to HIV testing in dental setting. POCT uptake in dental settings was comparable with other non-specialized health settings. Key to the operationalization of the intervention were perceptions about its value and relevance to the dental patient population, attitudes toward the intervention, logistical barriers to its implementation, the risk of HIV testing stigma to the patient-practitioner relationship and maximising the fit of the intervention within the constraints of the dental setting.

Role of FeNO in predicting the responsiveness of inhaled corticosteroids in COPD: a systematic review.

Fractional exhaled nitric oxide (FeNO) as a predictor of inhaled corticosteroid (ICS) response in asthma has been established. However, the same has not been established in chronic obstructive pulmonary disease (COPD). An optimal value of FeNO for prescribing and monitoring ICS response has not been quantified. To examine the evidence for this association. A systematic review was conducted of randomised controlled trials and observational studies examining the association between FeNO level and response to ICS in COPD patients. All studies examining this association were included. Five databases were searched thoroughly. Systematic screening, full-text reviews, and data extraction were carried out based on eligibility criteria. A total of 8690 studies were identified, 342 texts were screened fully, and six studies were included for the final review. One was a randomised controlled trial and the other five were non-randomised interventional trials. One study was conducted in asthma-COPD overlap (ACO patients). After ICS use, three studies found statistically significant correlations between FeNO and lung function improvement (FEV1), and three studies also found significant correlations between FeNO and COPD quality-of-life scores. Measurement of FeNO is non-invasive and standardised, with results available at the point of testing. Because of the small sample size and short duration of studies, exacerbation frequencies were not measured. Despite this, the review suggests that FeNO may be a potential biomarker for assessing ICS response in COPD. Further research that stratifies patients by FeNO levels and assesses the impact on acute exacerbations is needed to understand its potential value in routine clinical practice.

Comparison of indirect cyanmethaemoglobin method and TrueHb haemometer point of care test with direct cyanmethaemoglobin (gold standard) method for strengthening anaemia detection at primary health care level

ABSTRACT Introduction: The most reliable indicator for anaemia diagnosis at the population level is haemoglobin (Hb) estimation. The direct cyanmethaemoglobin method is considered the gold standard method for haemoglobin estimation. However, for resource constraint areas like primary health care (PHC) level, either blood samples are transported on filter paper for Hb testing (indirect cyanmethaemoglobin method) in laboratory or point of care testing is commonly used. Therefore, a comparative analysis of haemoglobin estimation of direct with indirect cyanmethaemoglobin method and also with TrueHb (Wrig Nanosystems Pvt. Ltd.) haemometer was done to strengthen anaemia diagnosis at the PHC level. Materials and Methods: This was a cross-sectional study. A total of 90 participants above 9 years of age, who visited the outpatient department (OPD) of health centre, Kheri and gave consent were included. Comparative analysis was done between Hb concentration assessed by indirect cyanmethaemoglobin method and TrueHb haemometer device against the gold standard method. Results: The mean Hb value estimated by direct method, TrueHb haemometer and indirect methods (filter paper A, B and C) was 11.42 ± 1.59 g/dl, 11.52 ± 1.54 g/dl, 10.66 ± 1.52 g/dl, 9.84 ± 1.50 g/dl and 10.19 ± 1.62 g/dl, respectively. There was no significant difference found between the mean Hb concentration estimated by the direct method and the TrueHb haemometer device. However, there was a significant difference in mean Hb values between the direct method and the indirect method. Therefore, regression analysis was done to estimate the correction factor for the indirect method. Conclusion: TrueHb metre device gave promising results in comparison to the gold standard method and can be used if resource permits in PHC centres. Indirect methods of haemoglobin estimation can be an alternative in resource-constraint settings, specifically for surveys. However, further studies are required for the validation of the indirect method.

Research on Temperature Field Characteristics of Lithium Battery Vacuum Drying Furnace

The temperature distribution of the vacuum contact drying oven fixture is a crucial factor that affects the moisture characteristics of the electric core. This paper presents a study on the temperature characteristics of the vacuum oven fixture, which combines theoretical analysis, numerical calculation, and experimental research. The results indicate that during the temperature rise process, the fixture temperature center intersects elliptically with the surrounding diffusion, while the temperature center of the insulation process is circular to the surrounding diffusion. Additionally, the temperature increase at each test point during the PID control process first increases and then decreases with time, gradually reaching stability. The temperature difference between the test points meets the process requirements. The research results obtained for the design of the vacuum oven fixture provide theoretical reference for addressing temperature control issues and practical guidance for production.

School urinary screening program in Japan: history, outcomes, perspectives.

In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney diseases at an early stage. While the American Academy of Pediatrics recommended discontinuing urinalysis as a public health service in 2007, urinary screening in Japan has proven extremely successful in reducing the incidence of kidney failure with replacement therapy in children and young adults, especially through the early treatment of glomerulonephritis, such as immunoglobulin A nephropathy. Furthermore, the positivity rate on urinary screening in Japan is significantly lower than in the United States where the rate of false positive results is typically very high. Japan's seamless and efficient pediatric urinary screening may be a helpful example for other countries as well. However, the present investigation revealed several, unresolved problems with the system. For example, the methods used varied in terms of their cutoff point, additional examinations, and types of detailed testing. In Japan, various urinary screening methods are being tested to optimize the system for national use. Recently, the authors also recommended a system of detailed examinations, including beta-2 microglobulin testing and ultrasonography, to detect congenital anomalies of the kidney and urinary tract, the most common, underlying disease in kidney failure with replacement therapy, which is often overlooked until the symptoms have become grave. While school urinary screening has been ongoing for about 50 years and should be continued, improvements should also be made to it as needed.

Lung Clearance Index as a Screening Parameter of Pulmonary Impairment in Patients under Immune Checkpoint Therapy: A Pilot Study.

Background: Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways. Methods: This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement. Results: Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant (p = 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing (p = 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25-75%) in the ICB-treated patients was significantly reduced (p = 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group (p = 0.734). Conclusions: The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation.

Supratherapeutic INR During Treatment With Nirmatrelvir/Ritonavir and Warfarin and Acute Illness With COVID-19: A Case Report

Background: Several studies have examined INR fluctuations using pharmacokinetic (PK) models or post-hoc INR values after completing nirmatrelvir/ritonavir, but further study of the effects of the drug interaction with warfarin during treatment is necessary. Case Summary: Nirmatrelvir/ritonavir is largely utilized in the outpatient setting so data regarding INR trends in hospitalized patients on warfarin is limited. However, many who receive nirmatrelvir/ritonavir outpatient experience difficulty with presenting to clinic for INR checks due to feeling acutely ill along with isolation precautions. We present the case of a patient receiving warfarin and utilizing home INR testing for monitoring. After diagnosis of coronavirus disease of 2019 (COVID-19), she was started on nirmatrelvir/ritonavir on day five after testing positive. Most recent INR prior to the start of therapy was 2.7 and had been stable on the same dose for months prior to infection. On day two of nirmatrelvir/ritonavir, her INR rose to 4.0 on home point of care INR testing. Despite reducing her dose of warfarin by 15%, her INR remained supratherapeutic the day after completing nirmatrelvir/ritonavir (4.0) and for several checks after. One month after completion of therapy, her INR returned to therapeutic levels. Practice Implications: While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19.

Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency.

Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk. This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre. Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%. This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.