Lag times to steady state drug delivery by continuous intravenous infusion: direct comparison of peristaltic and syringe pump performance identifies contributions from infusion system dead volume and pump startup characteristics.

Time lags between the initiation of a continuous drug infusion and achievement of a steady state delivery rate present an important safety concern. At least 3 factors contribute to these time lags: (1) dead volume size, (2) the ratio between total system flow and dead volume, and (3) startup delay. While clinicians employ both peristaltic pumps and syringe pumps to propel infusions, there has been no head-to-head comparison of drug delivery between commercially available infusion pumps with these distinct propulsion mechanisms. We quantified the delivery of a model drug by peristaltic and syringe pumps at clinically relevant flow rates using spectrophotometric absorbance. Delivery curves were modeled and compared, and the time required to reach 5% (T5), 50% (T50), and 95% (T95) of the intended delivery rate was reported. The ability to overcome the combined effects of startup delay and dead volume differed between syringe and peristaltic pumps. T5, T50, and T95 were shorter for the peristaltic pump at higher flow rates. T50 and T95 were shorter for the syringe pump at lower flow rates. The ability to overcome the effects of dead volume was overall similar between the syringe and peristaltic pumps, as was the response to consecutive changes in drug infusion rates. Startup delay and dead volume in carrier-based infusion systems cause substantial time lags to reaching intended delivery rates. Peristaltic and syringe pumps are similarly susceptible to dead volume effects. Startup performance differed between peristaltic and syringe pumps; their relative performance may be dependent on flow rate.

Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

The Efficacy of Liposomal Bupivacaine for Opioid and Pain Reduction: A Systematic Review of Randomized Clinical Trials.

Background The opioid crisis has prompted surgeons to search for alternative postoperative methods of analgesia. Liposomal bupivacaine is a long-acting local anesthetic formulation used for pain, potentially reducing opioid use. Evaluation of liposomal bupivacaine as a viable alternative for pain management is needed. The objective was to assess the efficacy of randomized clinical trials (RCTs) of liposomal bupivacaine in postoperative pain management and opioid consumption. Material and Methods The authors extracted RCTs comparing liposomal bupivacaine versus placebo or active comparators for postoperative pain or opioid reduction from PubMED/MEDLINE, Cochrane Library, and ClinicalTrials.gov. Exclusion criteria included nonhuman studies, non-RCTs, pooled studies, and inability to access full text. The following variables were abstracted: surgical specialty, number of subjects, pain and opioid outcomes, and authors' financial conflicts of interest. Results We identified 77 published RCTs, of which 63 studies with a total of 6770 subjects met inclusion criteria. Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs. Of the studies evaluating narcotic use, liposomal bupivacaine did not show a reduction in opioid consumption in 85.71% of RCTs. Liposomal bupivacaine, when compared to standard bupivacaine or another active agent, yielded no reduction in opioid use in 83.33% and 100.00% of studies, respectively. Clinical trials with a financial conflict of interest relating to the manufacturer of liposomal bupivacaine were significantly more likely to show pain relief (OR: 14.31 [95% CI, 2.8, 73.10], P = 0.0001) and decreased opioid consumption (OR: 12.35 [95% CI 1.40, 109.07], P = 0.0237). Of the 265 unpublished RCTs on ClinicalTrials.gov, 47.54% were withdrawn, terminated, suspended, or completed without study results available. Conclusions The efficacy of liposomal bupivacaine for providing superior postoperative pain control relative to placebo or another active agent is not supported by a majority of RCTs. Underreporting of trial results and bias due to underlying financial relationships amongst authors are two major concerns that should be considered when evaluating the available evidence.

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

BACKGROUND: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. METHODS: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. RESULTS: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = -0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. CONCLUSIONS: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. TRIAL REGISTRATION: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393.

A systematic review of reviews identifying UK validated dietary assessment tools for inclusion on an interactive guided website for researchers: www.nutritools.org.

Background: Health researchers may struggle to choose suitable validated dietary assessment tools (DATs) for their target population. The aim of this review was to identify and collate information on validated UK DATs and validation studies for inclusion on a website to support researchers to choose appropriate DATs.Design: A systematic review of reviews of DATs was undertaken. DATs validated in UK populations were extracted from the studies identified. A searchable website was designed to display these data. Additionally, mean differences and limits of agreement between test and comparison methods were summarized by a method, weighting by sample size.Results: Over 900 validation results covering 5 life stages, 18 nutrients, 6 dietary assessment methods, and 9 validation method types were extracted from 63 validated DATs which were identified from 68 reviews. These were incorporated into www.nutritools.org. Limits of agreement were determined for about half of validations. Thirty four DATs were FFQs. Only 17 DATs were validated against biomarkers, and only 19 DATs were validated in infant/children/adolescents.Conclusions: The interactive www.nutritools.org website holds extensive validation data identified from this review and can be used to guide researchers to critically compare and choose a suitable DAT for their research question, leading to improvement of nutritional epidemiology research.

In-hospital airway management of COVID-19 patients.

Those involved in the airway management of COVID-19 patients are particularly at risk. Here, we describe a practical, stepwise protocol for safe in-hospital airway management in patients with suspected or confirmed COVID-19 infection.

Application of Lung Ultrasound During the COVID-19 Pandemic: A Narrative Review.

This review highlights the ultrasound findings reported from a number of studies and case reports and discusses the unifying findings from coronavirus disease (COVID-19) patients and from the avian (H7N9) and H1N1 influenza epidemics. We discuss the potential role for portable point-of-care ultrasound (PPOCUS) as a safe and effective bedside option in the initial evaluation, management, and monitoring of disease progression in patients with confirmed or suspected COVID-19 infection.

Comparison of Invasive and Noninvasive Blood Pressure Measurements for Assessing Signal Complexity and Surgical Risk in Cardiac Surgical Patients.

BACKGROUND: Continuous arterial blood pressure (ABP) is typically recorded by placement of an intraarterial catheter. Recently, noninvasive ABP monitors have been shown to be comparable in accuracy to invasive measurements. In a previous study, we showed that the fluctuations in beat-to-beat ABP measurements were not random variations but had a complex dynamical structure, and that ABP dynamical complexity was inversely associated with surgical risk estimated using the Society of Thoracic Surgeons (STS) index. Dynamical complexity is a mathematical construct that reflects the capacity of a physiological system to adapt to stimuli. The objectives of present study were to: (1) determine whether noninvasive beat-to-beat ABP measurements also exhibit a complex temporal structure; (2) compare the complexity of noninvasive versus invasive ABP time series; and (3) quantify the relationship between the complexity of noninvasive ABP time series and the STS risk scores. METHODS: Fifteen adult patients undergoing coronary artery bypass graft, valve, or combined coronary artery bypass graft/valve surgery were enrolled in this observational study. Preoperative ABP waveforms were simultaneously recorded for ≥15 minutes using a radial artery catheter (invasive) and a continuous noninvasive arterial pressure monitor. Beat-to-beat systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) time series were extracted from the continuous waveforms. Complexity was assessed using the multiscale entropy method. The Wilcoxon signed-rank test was used to compare the mean ranks of indices derived from invasive versus noninvasive ABP time series. Spearman correlation coefficients were used to quantify the relationship between invasive and noninvasive indices. Linear regression analysis was used to quantify the association between each of the complexity indices and the STS risk scores. RESULTS: Beat-to-beat fluctuations in noninvasive ABP measurements were not random but complex; however, their degree of complexity was lower than that of fluctuations in invasively obtained ABP signals (SBP: 7.05 vs 8.66, P < .001; DBP: 7.40 vs 8.41, P < .001; PP: 6.83 vs 8.82, P < .001; and MAP: 7.17 vs 8.68, P < .005). Invasive and noninvasive indices for MSEΣ·slope showed good correlation (rs) (0.53 for SBP, 0.79 for DBP, 0.42 for PP, 0.60 for MAP). The complexity of noninvasive ABP time series (-0.70 [-1.28 to -0.11]; P = .023 for DBP), like that of invasive time series (-0.94 [-1.52 to -0.35]; P = .004 for DBP), was inversely associated with estimated surgical risk in patients undergoing cardiovascular operations. CONCLUSIONS: Our results support the use of noninvasive ABP monitoring in computations of complexity-based indices that correlate with estimated surgical risk.

Plasmodium falciparum HRP2 ELISA for analysis of dried blood spot samples in rural Zambia.

BACKGROUND: Dried blood spots are commonly used for sample collection in clinical and non-clinical settings. This method is simple, and biomolecules in the samples remain stable for months at room temperature. In the field, blood samples for the study and diagnosis of malaria are often collected on dried blood spot cards, so development of a biomarker extraction and analysis method is needed. METHODS: A simple extraction procedure for the malarial biomarker Plasmodium falciparum histidine-rich protein 2 (HRP2) from dried blood spots was optimized to achieve maximum extraction efficiency. This method was used to assess the stability of HRP2 in dried blood spots. Furthermore, 328 patient samples made available from rural Zambia were analysed for HRP2 using the developed method. These samples were collected at the initial administration of artemisinin-based combination therapy and at several points following treatment. RESULTS: An average extraction efficiency of 70% HRP2 with a low picomolar detection limit was achieved. In specific storage conditions HRP2 was found to be stable in dried blood spots for at least 6 months. Analysis of patient samples showed the method to have a sensitivity of 94% and a specificity of 89% when compared with microscopy, and trends in HRP2 clearance after treatment were observed. CONCLUSIONS: The dried blood spot ELISA for HRP2 was found to be sensitive, specific and accurate. The method was effectively used to assess biomarker clearance characteristics in patient samples, which prove it to be ideal for gaining further insight into the disease and epidemiological applications.

Magnetically-enabled biomarker extraction and delivery system: towards integrated ASSURED diagnostic tools.

Diagnosis of asymptomatic malaria poses a great challenge to global disease elimination efforts. Healthcare infrastructure in rural settings cannot support existing state-of-the-art tools necessary to diagnose asymptomatic malaria infections. Instead, lateral flow immunoassays (LFAs) are widely used as a diagnostic tool in malaria endemic areas. While LFAs are simple and easy to use, they are unable to detect low levels of parasite infection. We have developed a field deployable Magnetically-enabled Biomarker Extraction And Delivery System (mBEADS) that significantly improves limits of detection for several commercially available LFAs. Integration of mBEADS with leading commercial Plasmodium falciparum malaria LFAs improves detection limits to encompass an estimated 95% of the disease reservoir. This user-centered mBEADS platform makes significant improvements to a previously cumbersome malaria biomarker enrichment strategy by improving reagent stability, decreasing the processing time 10-fold, and reducing the assay cost 10-fold. The resulting mBEADS process adds just three minutes and less than $0.25 to the total cost of a single LFA, thus balancing sensitivity and practicality to align with the World Health Organization's ASSURED criteria for point-of-care (POC) testing.

Attenuated Positive Psychotic Symptoms in Relation to Cigarette Smoking in a Nonclinical Population.

INTRODUCTION: This study explored the association between cigarette smoking and attenuated positive psychotic symptoms in a young adult nonclinical sample. METHODS: Undergraduates (N = 930), aged 18-35 years (26.3% male), completed a battery of self-report measures assessing subthreshold psychotic symptoms, cigarette smoking behavior/dependence, and drug use. RESULTS: Individuals endorsing a greater number of attenuated positive psychotic symptoms were more likely to be smokers. Exploratory analyses indicated that the odds of being a smoker were two times greater for those at potential higher risk for psychosis compared with individuals at lower risk. Results were consistent after adjusting for sex and other drug use. CONCLUSIONS: In line with findings from psychotic populations, results suggest that attenuated positive psychotic symptoms, particularly those endorsed as distressing in a nonclinical, undergraduate population, are related to cigarette smoking. IMPLICATIONS: Even in nonclinical, undergraduate populations, subthreshold psychotic symptoms are related to cigarette smoking, and cigarette smokers are twice as likely to be considered at potentially higher risk for psychosis compared with noncigarette smokers. In summary, there may be a threshold whereby psychotic symptoms confer increased risk for nicotine consumption, with endorsement of a greater number of distressing subthreshold psychotic symptoms increasing the likelihood of cigarette use.

Sensitive Method for Biomolecule Detection Utilizing Signal Amplification with Porphyrin Nanoparticles.

Disease diagnosis requires identification of biomarkers that occur in small quantities, making detection a difficult task. Effective diagnosis is an even greater challenge in low-resource areas of the world. Methods must be simple, stable, and sensitive so that tests can be easily administered and withstand uncontrolled environmental conditions. One approach to this issue is development of stable signal amplification strategies. In this work, we applied the nanocrystal-based signal amplification method to tetra(4-carboxyphenyl)porphyrin nanoparticles (TCPP NPs). The dissolution of the nanoparticle into thousands of porphyrin molecules results in amplified detection of the biomarker. By using nanoparticles as the signal-generating moiety, stability of the detection method is increased relative to commonly used enzyme-based assays. Additionally, the inherent fluorescent signal of TCPP molecules can be measured after nanoparticle dissolution. The ability to directly read the TCPP fluorescent signal increases assay simplicity by reducing the steps required for the test. This detection method was optimized by detecting rabbit IgG and then was applied to the detection of the malarial biomarker Plasmodium falciparum histidine-rich protein II (pfHRPII) from a complex matrix. The results for both biomarkers were assays with low picomolar limits of detection.

Longitudinal Strain Patterns in Stress (Takotsubo) Cardiomyopathy: Evidence of Global Myocardial Injury and Incomplete Recovery.

Stress cardiomyopathy develops after abrupt sympathetic stimulation, likely from catecholamine-induced myocardial toxicity. The evolution of myocardial strain during and after an episode have not been previously characterized. We aimed to determine whether preexisting contractile abnormalities may explain the observed regional dysfunction during an acute episode and to investigate the persistence of strain abnormalities after clinical recovery. We identified patients who were diagnosed with stress cardiomyopathy and had an echocardiogram performed before their episode, during their episode, and within 1 year after. The diagnosis was confirmed based on the absence of obstructive coronary lesions. Left ventricular (LV) longitudinal strain was calculated using speckle-tracking software and compared between baseline, episode, and follow-up echocardiograms. The LV strain analysis was performed on 23 patients. The LV ejection fraction was 64 ± 8.7% at baseline, 45 ± 12% during the episode, and 5 9 ± 10% after a median follow-up of 46 days. The LV global longitudinal strain was 24 ± 4.7% at baseline, 11 ± 4.9% during the episode, and 19 ± 4.6% after the follow-up. The mean ejection fraction (p <0.01) and global longitudinal strain (p <0.001) remained below baseline levels at follow-up. Longitudinal strain was reduced (<18%) in 80 ± 23% of myocardial segments during an episode and 41 ± 21% of myocardial segments at follow-up. During the acute episode, 35 ± 6% of the abnormal segments were in the base, outside of the region of ballooning. Our findings suggests that stress cardiomyopathy is associated with global rather than regional myocardial injury and that contractile abnormalities persist after clinical improvement. These findings challenge our previous understanding of stress cardiomyopathy and may guide future pathophysiologic understanding of this complex disease.

An Assessment of Carotid Flow Time Using a Portable Handheld Ultrasound Device: The Ideal Tool for Guiding Intraoperative Fluid Management?

Volume resuscitation is a cornerstone of modern anesthesia care. Finding the right balance to avoid inadequate or excess volume administration is often difficult to clinically discern and can lead to negative consequences. Pulse pressure variation is often intraoperatively used to guide volume resuscitation; however, this requires an invasive arterial line and is generally only applicable to patients who are mechanically ventilated. Unfortunately, without a pulmonary artery catheter or another costly noninvasive device, performing serial measurements of cardiac output is challenging, time-consuming, and often impractical. Furthermore, noninvasive measures such as LVOT VTI require significant technical expertise as well as access to the chest, which may not be practical during and after surgery. Other noninvasive techniques such as bioreactance and esophageal Doppler require the use of costly single-use sensors. Here, we present a case report on the use of corrected carotid flow time (ccFT) from a portable, handheld ultrasound device as a practical, noninvasive, and technically straightforward method to assess fluid responsiveness in the perioperative period, as well as the inpatient and outpatient settings.

Portable Handheld Point-of-Care Ultrasound for Detecting Unrecognized Esophageal Intubations.

Esophageal intubations are not an uncommon occurrence in prehospital settings, occurring as high as 17%. These "never events" are associated with significant morbidity and mortality especially when unrecognized or when there is delayed recognition. Here, we review the currently available techniques for confirming endotracheal tube intubation and their limitations, and present the case for the application of portable handheld point-of-care ultrasound as an emerging technology for detection of potentially unrecognized esophageal intubations such as during cardiac arrest. We also provide algorithms for confirmation of tracheal intubation.

Usability of myfood24 Healthcare and Mathematical Diet Optimisation in Clinical Populations: A Pilot Feasibility Randomised Controlled Trial.

Monitoring nutritional intake is of clinical value, but few existing tools offer electronic dietary recording, instant nutritional analysis, and a platform connecting healthcare teams with patients that provides timely, personalised support. This feasibility randomised controlled trial tests the usability of 'myfood24 Healthcare', a dietary assessment app and healthcare professional website, in two clinical populations. Patients were recruited from a weight management programme (n21) and from a group of gastroenterology surgery outpatients (n = 27). They were randomised into three groups: standard care, myfood24, or myfood24 + diet optimisation (automated suggestions for dietary improvement). The participants were asked to record their diet at least four times over eight weeks. During the study, healthcare professionals viewed recorded dietary information to facilitate discussions about diet and nutritional targets. The participants provided feedback on usability and acceptability. A total of 48 patients were recruited, and 16 were randomised to each of the three groups. Compliance among app users (n = 32) was reasonable, with 25 (78%) using it at least once and 16 (50%) recording intake for four days or more. Among users, the mean (standard deviation) number of days used was 14.0 (17.5), and the median (interquartile range) was six (2.5-17.0) over 2 months. Feedback questionnaires were completed by only 23 of 46 participants (50%). The mean System Usability Score (n = 16) was 59 (95% confidence interval, 48-70). Patient and healthcare professional feedback indicates a need for more user training and the improvement of some key app features such as the food search function. This feasibility study shows that myfood24 Healthcare is acceptable for patients and healthcare professionals. These data will inform app refinements and its application in a larger clinical effectiveness trial.