Leveraging IoTs and Machine Learning for Patient Diagnosis and Ventilation Management in the Intensive Care Unit.

Future healthcare systems will rely heavily on clinical decision support systems (CDSS) to improve the decision-making processes of clinicians. To explore the design of future CDSS, we developed a research-focused CDSS for the management of patients in the intensive care unit that leverages Internet of Things (IoT) devices capable of collecting streaming physiologic data from ventilators and other medical devices. We then created machine learning (ML) models that could analyze the collected physiologic data to determine if the ventilator was delivering potentially harmful therapy and if a deadly respiratory condition, acute respiratory distress syndrome (ARDS), was present. We also present work to aggregate these models into a mobile application that can provide responsive, real-time alerts of changes in ventilation to providers. As illustrated in the recent COVID-19 pandemic, being able to accurately predict ARDS in newly infected patients can assist in prioritizing care. We show that CDSS may be used to analyze physiologic data for clinical event recognition and automated diagnosis, and we also highlight future research avenues for hospital CDSS.

A seroprevalence study to determine the frequency of hantavirus infection in people exposed to wild and pet fancy rats in England.

Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9-45·7%) compared with 3·3% (95% CI 1·6-6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6-5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2-5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.

High prevalence of Seoul hantavirus in a breeding colony of pet rats.

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

Balloon dilation atrial septostomy for advanced pulmonary hypertension in patients on prostanoid therapy.

BACKGROUND: Prostanoid therapy improves quality of life and may increase survival in patients with advanced pulmonary hypertension (PH). Balloon dilated atrial septostomy (BDAS) can palliate or bridge to transplantation for patients resistant to medical therapy. The safety and efficacy of BDAS in the prostanoid era has not previously been reported. METHODS: All patients had progressive symptoms despite prostanoid therapy at the time of their first BDAS. Sixteen patients who underwent a total of 23 septostomies between 2004 and 2014 were included in this retrospective case series. RESULTS: Patients were aged 47.6 years ± 11.3 with 12/16 women. Etiologies included idiopathic (7), methamphetamine (6), scleroderma (1), and anorexigen (2). One patient died within 24 hr post-procedure. Thirty-day and 1-year survival were 75% and 64%, respectively. Six of the septostomies were revisions, including two which were ultimately stented. Three subjects were successfully bridged to transplant. Pulmonary capillary wedge pressure (PCWP) increased from a mean of 13 to 17 mm Hg, cardiac index increased from 2.1 to 2.4 L/min/m(2) , and arterial saturation decreased from 90.7 ± 4.3 to 82.5 ± 5.6%. All non-survivors at 30 days were male and had higher baseline serum creatinine, mean RAP, right ventricular end diastolic pressure (RVEDP), and left ventricle (LV) filling pressures, and lower right ventricle (RV) ejection fraction. Mortality was associated with unchanged post-septostomy cardiac output despite an increase in left ventricular end diastolic pressure (LVEDP). CONCLUSIONS: BDAS may be an alternate therapy for select PH patients who have symptomatic progression despite prostanoid therapy. Survival is comparable to prior reports of BDAS in the pre-prostanoid era.

Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, Western Area, Sierra Leone, January to February 2015.

Current Ebola virus disease (EVD) diagnosis relies on reverse transcription-PCR (RT-PCR) technology, requiring skilled laboratory personnel and technical infrastructure. Lack of laboratory diagnostic capacity has led to diagnostic delays in the current West African EVD outbreak of 2014 and 2015, compromising outbreak control. We evaluated the diagnostic accuracy of the EVD bedside rapid diagnostic antigen test (RDT) developed by the United Kingdom's Defence Science and Technology Laboratory, compared with Ebola virus RT-PCR, in an operational setting for EVD diagnosis of suspected cases admitted to Ebola holding units in the Western Area of Sierra Leone. From 22 January to 16 February 2015, 138 participants were enrolled. EVD prevalence was 11.5%. All EVD cases were identified by a positive RDT with a test line score of 6 or more, giving a sensitivity of 100% (95% confidence interval (CI): 78.2-100). The corresponding specificity was high (96.6%, 95% CI: 91.3-99.1). The positive and negative predictive values for the population prevalence were 79.0% (95% CI: 54.4-93.8) and 100% (95% CI: 96.7-100), respectively. These results, if confirmed in a larger study, suggest that this RDT could be used as a 'rule-out' screening test for EVD to improve rapid case identification and resource allocation.

Improving Wildfire Readiness Among Patients With Chronic Obstructive Pulmonary Disease and Asthma: Applying a Population Health Approach to Climate Change.

As a result of climate change, wildfire frequency, duration, and severity are increasing in the United States. Exposure to wildfire-related air pollutants can lead to negative health outcomes, particularly among patients with pre-existing respiratory diseases (eg, asthma and chronic obstructive pulmonary disease) and those who are at higher risk for developing these conditions. Underserved communities are disproportionately affected for multiple reasons, including lack of financial and social resources, increased exposure to air pollutants at home and at work, and impaired access to healthcare. To best serve clinically high-risk and underserved populations, health systems must leverage community public health data, develop and mobilize a wildfire preparedness action plan to identify populations at high risk, and implement interventions to mitigate the consequences of poor air quality. University of California, Davis Health, located at the epicenter of the largest wildfires in California's history, has developed the 5 pillar Wildfire Population Health Approach: (1) identify clinically at-risk and underserved patient populations using well-validated, condition-targeted registries; (2) assemble multidisciplinary care teams to understand the needs of these communities and patients; (3) create custom analytics and wildfire-risk stratification; (4) develop care pathways based on wildfire-risk tiers by disease, risk of exposure, and healthcare access; and (5) identify outcome measures tailored to interventions with a commitment to continuous, iterative improvement efforts. The Wildfire Population Health Approach provides an action plan for health systems and care teams to meet the needs of clinically at-risk and underserved patients affected by the increasing health threat posed by climate change-related wildfires.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency: A Phase 1 Study.

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT. Methods: In this phase 1 dose-escalation study (N=31), adults with AATD received 1 dose (part 1) or 3 doses (part 2) of 10 (part 1), 40, 80, or 120mg/kg INBRX-101 every 3 weeks (Q3W) via intravenous infusion. The primary endpoint was safety and tolerability. Secondary endpoints were pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of INBRX-101. Results: INBRX-101 was well tolerated. Most treatment-emergent adverse events were grade ≤2. In part 2 (n=18; each dose, n=6), dose-related increases in serum functional AAT (fAAT) were observed; mean fAAT levels remained above the 21 µM target for up to 4 weeks after the final dose in the 120-mg/kg cohort. Antidrug antibodies had no meaningful impact on PK or PD. INBRX-101 was detected in pulmonary epithelial lining fluid (PELF) from all patients assessed (n=11), and PELF fAAT increased after dosing. PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM). Conclusion: The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101.

The continued emergence of hantaviruses: isolation of a Seoul virus implicated in human disease, United Kingdom, October 2012.

Following a suspected case of hantavirus in a patientsuffering from acute kidney injury, rodents fromthe patient's property in Yorkshire and the Humber,United Kingdom (UK) were screened for hantaviruses.Hantavirus RNA was detected via RT-PCR in two Rattusnorvegicus. Complete sequencing and phylogeneticanalysis established the virus as a Seoul hantavirus,which we have provisionally designated as strainHumber. This is the first hantavirus isolated from wildrodents in the UK and confirms the presence of a pathogenicSeoul virus in Europe.

Work of Breathing During Proportional Assist Ventilation as a Predictor of Extubation Failure.

BACKGROUND: Despite decades of research on predictors of extubation success, use of ventilatory support after extubation is common and 10-20% of patients require re-intubation. Proportional assist ventilation (PAV) mode automatically calculates estimated total work of breathing (total WOB). Here, we assessed the performance of total WOB to predict extubation failure in invasively ventilated subjects. METHODS: This prospective observational study was conducted in 6 adult ICUs at an academic medical center. We enrolled intubated subjects who successfully completed a spontaneous breathing trial, had a rapid shallow breathing index < 105 breaths/min/L, and were deemed ready for extubation by the primary team. Total WOB values were recorded at the end of a 30-min PAV trial. Extubation failure was defined as any respiratory support and/or re-intubation within 72 h of extubation. We compared total WOB scores between groups and performance of total WOB for predicting extubation failure with receiver operating characteristic curves. RESULTS: Of 61 subjects enrolled, 9.8% (n = 6) required re-intubation, and 50.8% (n = 31) required any respiratory support within 72 h of extubation. Median total WOB at 30 min on PAV was 0.9 J/L (interquartile range 0.7-1.3 J/L). Total WOB was significantly different between subjects who failed or were successfully extubated (median 1.1 J/L vs 0.7 J/L, P = .004). The area under the curve was 0.71 [95% CI 0.58-0.85] for predicting any requirement of respiratory support and 0.85 [95% CI 0.69-1.00] for predicting re-intubation alone within 72 h of extubation. Total WOB cutoff values maximizing sensitivity and specificity equally were 1.0 J/L for any respiratory support (positive predictive value [PPV] 70.0%, negative predictive value [NPV] 67.7%) and 1.3 J/L for re-intubation (PPV 26.3%, NPV 97.6%). CONCLUSIONS: The discriminative performance of a PAV-derived total WOB value to predict extubation failure was good, indicating total WOB may represent an adjunctive tool for assessing extubation readiness. However, these results should be interpreted as preliminary, with specific thresholds of PAV-derived total WOB requiring further investigation in a large multi-center study.

False-negative FAST examination: associations with injury characteristics and patient outcomes.

STUDY OBJECTIVE: Focused assessment with sonography in trauma (FAST) is widely used for evaluating patients with blunt abdominal trauma; however, it sometimes produces false-negative results. Presenting characteristics in the emergency department may help identify patients at risk for false-negative FAST result or help the physician predict injuries in patients with a negative FAST result who are unstable or deteriorate during observation. Alternatively, false-negative FAST may have no clinical significance. The objectives of this study are to estimate associations between false-negative FAST results and patient characteristics, specific abdominal organ injuries, and patient outcomes. METHODS: This was a retrospective cohort study including consecutive patients who presented to an urban Level I trauma center between July 2005 and December 2008 with blunt abdominal trauma, a documented FAST, and pathologic free fluid as determined by computed tomography, diagnostic peritoneal lavage, laparotomy, or autopsy. Physicians blinded to the study purpose used standardized abstraction methods to confirm FAST results and the presence of pathologic free fluid. Multivariable modeling was used to assess associations between potential predictors of a false-negative FAST result and false-negative FAST result and adverse outcomes. RESULTS: During the study period, 332 patients met inclusion criteria. Median age was 32 years (interquartile range 23 to 45 years), 67% were male patients, the median Injury Severity Score was 27 (interquartile range 17 to 41), and 162 (49%) had a false-negative FAST result. Head injury was positively associated with false-negative FAST result (odds ratio [OR] 4.9; 95% confidence interval [CI] 1.5 to 15.7), whereas severe abdominal injury was negatively associated (OR 0.3; 95% CI 0.1 to 0.5). Injuries to the spleen (OR 0.4; 95% CI 0.24 to 0.66), liver (OR 0.36; 95% CI 0.21 to 0.61), and abdominal vasculature (OR 0.17; 95% CI 0.07 to 0.38) were also negatively associated with false-negative FAST result. False-negative FAST result was not associated with mortality (OR 0.89; 95% CI 0.42 to 1.9), prolonged ICU length of stay (relative risk 0.88; 95% CI 0.69 to 1.12), or total hospital length of stay (relative risk 0.92; 95% CI 0.76 to 1.12). However, patients with false-negative FAST results were substantially less likely to require therapeutic laparotomy (OR 0.31; 95% CI 0.19 to 0.52). CONCLUSION: Patients with severe head injuries and minor abdominal injuries were more likely to have a false-negative than true-positive FAST result. On the other hand, patients with spleen, liver, or abdominal vascular injuries are less likely to have false-negative FAST examination results. Adverse outcomes were not associated with false-negative FAST examination results, and in fact patients with false-negative FAST result were less likely to have a therapeutic laparotomy. Further studies are needed to assess the strength of these findings.

Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012.

A patient with fever, and haemorrhagic symptoms was admitted to a hospital in Glasgow on 2 October 2012. Since he had returned from Afghanistan, serum samples were sent for diagnosis at the Rare and Imported Pathogens Laboratory, where a real-time reverse transcriptase-PCR diagnosis of Crimean ­ Congo haemorrhagic fever was made within 3 hrs after receipt of the sample. Hereafter the patient was transferred to a high-security infectious diseases unit in London but died on 6 October.

Is point-of-care ultrasound accurate and useful in the hands of military medical technicians? A review of the literature.

Over the past decade, point-of-care ultrasound (US) use by nonphysician providers has grown substantially. The purpose of this article is to (1) summarize the literature evaluating military medics' facility at US, (2) more clearly define the potential utility of military prehospital US technology, and (3) lay a pathway for future research of military prehospital US. The authors performed a keyword search using multiple search engines. Each author independently reviewed the search results and evaluated the literature for inclusion. Of 30 studies identified, five studies met inclusion criteria. The applications included evaluation of cardiac activity, pneumothorax evaluation, and fracture evaluation. Additionally, a descriptive study demonstrated distribution of US exam types during practical use by Army Special Forces Medical Sergeants. No studies evaluated retention of skills over prolonged periods. Multiple studies demonstrate the feasibility of training military medics in US. Even under austere conditions, the majority of studies conclude that medic can perform US with a high degree of accuracy. Lessons learned from these studies tend to support continued use of US in out-of-hospital settings and exploration of the optimal curriculum to introduce this skill.

Remote patient monitoring in the management of chronic obstructive pulmonary disease.

Remote patient monitoring allows monitoring high-risk patients through implementation of an expanding number of technologies in coordination with a healthcare team to augment care, with the potential to provide early detection of exacerbation, prompt access to therapy and clinical services, and ultimately improved patient outcomes and decreased healthcare utilization.In this review, we describe the application of remote patient monitoring in chronic obstructive pulmonary disease including the potential benefits and possible barriers to implementation both for the individual and the healthcare system.

A 66-Year-Old Man With Subacute Cough and Worsening Dyspnea Previously Diagnosed With COVID-19 Pneumonia.

A 66-year-old man presented with subacute cough and worsening dyspnea. Labs were notable for moderate peripheral eosinophilia, and computed tomography (CT) scan demonstrated extensive crazy-paving throughout bilateral upper lung fields. Bronchoalveolar lavage (BAL) revealed macrophages with lipid-filled vacuoles and negative periodic acid-Schiff (PAS) stain. Further history obtained from the patient and family was notable for daily application of commercially available vapor rub to nares and intentional deep inhalation of nebulized fluids containing scented oils. The patient was diagnosed with exogenous lipoid pneumonia through an unusual route of lipid administration.

Interprofessional Near-Peer Mentoring Teams Enhance Cancer Research Training: Sustainable Approaches for Biomedical Workforce Development of Historically Underrepresented Students.

A cancer research training program explored different approaches for staffing their in-person and virtual programs for high school students. The inclusion of undergraduate near-peer mentors had a universal benefit when implemented across in-person and virtual training programs of one- and ten-week durations. Benefits are described for four stakeholder groups: the high school trainees, program staff, scientist partners, and peer mentors themselves. Peer mentors described that their involvement enhanced their own professional development and, for some, drove a new interest in cancer research. Scientist partners described that peer mentors helped translate their work in the virtual environment for high school students. High school trainees reported their sessions with peer mentors to be one of their favorite parts of the program. Interprofessional peer mentors were highly relatable to students and modeled communication and paths in biomedical research. Staff reported that peer mentors supported student engagement during community shadowing sessions, allowing staff to focus on developing the shadowing experiences with partners. The benefit of including peer mentors was substantial from all viewpoints explored. Their intensive inclusion in cancer research training programs supports sustainability and capacity building in biomedical workforce development.

Physiologically-Based Pharmacokinetic Modeling to Investigate the Effect of Maturation on Buprenorphine Pharmacokinetics in Newborns with Neonatal Opioid Withdrawal Syndrome.

Neonatal opioid withdrawal syndrome (NOWS) is a major public health concern whose incidence has paralleled the opioid epidemic in the United States. Sublingual buprenorphine is an emerging treatment for NOWS, but given concerns about long-term adverse effects of perinatal opioid exposure, precision dosing of buprenorphine is needed. Buprenorphine pharmacokinetics (PK) in newborns, however, is highly variable. To evaluate underlying sources of PK variability, a neonatal physiologically-based pharmacokinetic (PBPK) model of sublingual buprenorphine was developed using Simcyp (version 19.1). The PBPK model included metabolism by cytochrome P450 (CYP) 3A4, CYP2C8, UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT2B7, and UGT2B17, with additional biliary excretion. Maturation of metabolizing enzymes was incorporated, and default CYP2C8 and UGT2B7 ontogeny profiles were updated according to recent literature. A biliary clearance developmental profile was outlined using clinical data from neonates receiving sublingual buprenorphine as NOWS treatment. Extensive PBPK model validation in adults demonstrated good predictability, with geometric mean (95% confidence interval (CI)) predicted/observed ratios (P/O ratios) of area under the curve from zero to infinity (AUC0-∞ ), peak concentration (Cmax ), and time to reach peak concentration (Tmax ) equaling 1.00 (0.74-1.33), 1.04 (0.84-1.29), and 0.95 (0.72-1.26), respectively. In neonates, the geometric mean (95% CI) P/O ratio of whole blood concentrations was 0.75 (95% CI 0.64-0.87). PBPK modeling and simulation demonstrated that variability in biliary clearance, sublingual absorption, and CYP3A4 abundance are likely important drivers of buprenorphine PK variability in neonates. The PBPK model could be used to guide development of improved buprenorphine starting dose regimens for the treatment of NOWS.