Deploying a rapid point-of-care polymerase chain reaction test for SARS-CoV-2 in a clinical research unit to ensure healthy volunteer safety.

The entire world was severely affected by the outbreak of the SARS-CoV-2 virus. Early phase clinical research was no exception and clinical healthy volunteer trials were halted across the globe. To enable continuation of development of new drugs, we developed a testing strategy for nonsymptomatic trial participants in an early stage of the outbreak. A point-of-care polymerase chain reaction test combined with a gold standard polymerase chain reaction test and strict social distancing and hygiene measures limited the number of infected subjects entering our clinical research units and reduced further spread for the duration of the clinical trial. Thus, proving efficacy of this strategy to allow safe and effective continuation of early phase clinical trials during the COVID-19 pandemic.

An electronic decision support-based complex intervention to improve management of cardiovascular risk in primary health care: a cluster randomised trial (INTEGRATE).

OBJECTIVES: To determine whether a multifaceted primary health care intervention better controlled cardiovascular disease (CVD) risk factors in patients with high risk of CVD than usual care. DESIGN, SETTING: Parallel arm, cluster randomised trial in 71 Australian general practices, 5 December 2016 - 13 September 2019. PARTICIPANTS: General practices that predominantly used an electronic medical record system compatible with the HealthTracker electronic decision support tool, and willing to implement all components of the INTEGRATE intervention. INTERVENTION: Electronic point-of-care decision support for general practices; combination cardiovascular medications (polypills); and a pharmacy-based medication adherence program. MAIN OUTCOME MEASURES: Proportion of patients with high CVD risk not on an optimal preventive medication regimen at baseline who had achieved both blood pressure and low-density lipoprotein (LDL) cholesterol goals at study end. RESULTS: After a median 15 months' follow-up, primary outcome data were available for 4477 of 7165 patients in the primary outcome cohort (62%). The proportion of patients who achieved both treatment targets was similar in the intervention (423 of 2156; 19.6%) and control groups (466 of 2321; 20.1%; relative risk, 1.06; 95% CI, 0.85-1.32). Further, no statistically significant differences were found for a number of secondary outcomes, including risk factor screening, preventive medication prescribing, and risk factor levels. Use of intervention components was low; it was highest for HealthTracker, used at least once for 347 of 3236 undertreated patients with high CVD risk (10.7%). CONCLUSIONS: Despite evidence for the efficacy of its individual components, the INTEGRATE intervention was not broadly implemented and did not improve CVD risk management in participating Australian general practices. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000233426 (prospective).

Addressing Hospital-Acquired Hypoglycemia.

BACKGROUND: Hospitalized patients who have diabetes often experience hospital-acquired hypoglycemia, a potentially serious adverse event; as a result, management of this condition has become an important quality of care indicator in the inpatient environment. A growing body of research and evidence-based clinical guidelines support proper timing of point of care (POC) blood glucose (BG) measurements, mealtime insulin administration, and meal delivery to reduce the incidence of both hypoglycemic and hyperglycemic events. Monitoring and improving the timing of these three patient care interventions are recognized as a crucial step in the safe and effective care of patients with diabetes. PURPOSE: The objective of the QI project was to improve the timing of mealtime insulin administration related to bedside BG monitoring and meal delivery for patients with diabetes who receive mealtime insulin; a secondary goal was to decrease the number of episodes of recurrent hypoglycemia. The overall strategy was to change staff members' approach to mealtime insulin management from a series of individual tasks to a process-oriented collaborative approach. METHODS: Nurses on the medical-surgical unit at one hospital within a large health system formed a QI team with staff members in information technology and food and nutrition services. The team implemented an eight-week QI pilot project (July 3 to August 26, 2017) using a multidisciplinary approach to coordinate between POC BG measurement, mealtime insulin administration, and meal delivery. RESULTS: More than two years after the hospital-wide rollout of the practice change, follow-up analysis has shown that, on both noncritical and critical care units, recurrent hypoglycemia has decreased. For example, comparing data obtained in a six-month period before the pilot project (November 2016 through April 2017) with the same six-month period in 2018 and 2019, more than a year after the pilot project, the percentage of patient stays (admissions) on noncritical care units in which there was a recurrence of hypoglycemia fell from 41.8% (of 1,162 total hospital admissions) to 35.1% (of 792 total hospital admissions); similarly, the percentage of patient stays on critical care units in which recurrent hypoglycemia occurred decreased from 36.8% to 22.8%. CONCLUSIONS: Findings suggest that ensuring a consistent 30-minute window between POC BG measurement and meal delivery enabled nursing staff to perform timely POC BG measurements and administer a more optimal mealtime insulin dose. Increasing interdisciplinary communication, collaboration, and awareness of best practice guidelines relating to proper mealtime insulin administration resulted in a sustained improvement in timing between POC BG measurements and mealtime insulin administration and between mealtime insulin administration and meal delivery.

Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: from bench to bedside.

Cancer management has undergone significant improvements, which led to increased long-term survival rates among cancer patients. Radiotherapy (RT) has an important role in the treatment of thoracic tumors, including breast, lung, and esophageal cancer, or Hodgkin's lymphoma. RT aims to kill tumor cells; however, it may have deleterious side effects on the surrounding normal tissues. The syndrome of unwanted cardiovascular adverse effects of thoracic RT is termed radiation-induced heart disease (RIHD), and the risk of developing RIHD is a critical concern in current oncology practice. Premature ischemic heart disease, cardiomyopathy, heart failure, valve abnormalities, and electrical conduct defects are common forms of RIHD. The underlying mechanisms of RIHD are still not entirely clear, and specific therapeutic interventions are missing. In this review, we focus on the molecular pathomechanisms of acute and chronic RIHD and propose preventive measures and possible pharmacological strategies to minimize the burden of RIHD.

ADR databases for on-site clinical use: Potentials of summary of products characteristics.

Adverse drug reactions (ADRs) for all drugs in Europe are described in the legally approved Summary of Product Characteristics (SmPC). An overview of all ADRs of the patients' drug list can support healthcare staff to link patient symptoms to possible ADRs. We review the possibilities and challenges to extract ADR information from SmPCs or American Structured Product Labels and present the development of our semi-automated procedure for extraction of ADRs from the tabulated section in the SmPCs to create a database, named Bikt, which is regularly updated and used at point of care in Sweden. The existence of five major table formats for ADRs used in the SmPCs required the development of different parsing scripts. Manual checks for correctness for all content have to be performed. The quality of extraction was investigated for all SmPCs by measuring precision, recall and F1 scores and compared with other methods published. We conclude that it is possible to semi-automatically extract ADR information from SmPCs. However, clear technical and content guidelines and standards for ADR tables and terms from drug registration authorities would lead to improved extraction and usability of ADR information at point of care.

Eficacia de una vía de alta resolución en la evaluación del cólico renoureteral no complicado en un servicio de urgencias hospitalario: un ensayo clínico aleatorizado (Estudio STONE) / Efficacy of a fast-track pathway for managing uncomplicated renal orureteral colic in a hospital emergency department: the STONE randomized clinical trial of Sonography and Testing of a Nephrolithiasis Episode

OBJETIVO: Evaluar una vía de alta resolución (vía POC) que utiliza análisis en el punto de atención (point-of-care testing-POCT-) y ecografía en el punto de atención (point-of-care ultrasonography -POCUS-) en la sospecha del cólico renoureteral (CRU) no complicado y compararla con la vía estándar (vía STD). MÉTODO: Ensayo clínico aleatorizado, controlado, no ciego, realizado en un servicio de urgencias hospitalario (SUH). Incluyó pacientes con sospecha clínica de CRU agudo y se aleatorizaron 1:1 a seguir vía POC o vía STD. Se analizó el tiempo de estancia en el SUH, el tratamiento administrado, la proporción de diagnósticos alternativos a CRU y las complicaciones a 30 días. RESULTADOS: Entre noviembre de 2018 y octubre de 2019, se reclutaron 140 pacientes de los que se analizaron 124.El tiempo de estancia total en el SUH de la vía POC fue de 112 minutos (DE 45) y en la vía STD 244 minutos (DE102) (p < 0,001). No hubo diferencias en el tratamiento administrado en urgencias, en el número de diagnósticos alternativos, ni en las complicaciones a 30 días. CONCLUSIONES: La utilización de una vía de alta resolución del manejo del CRU en un SUH es eficaz, segura y reduce el tiempo de estancia en urgencias

OBJECTIVES: To evaluate a fast-track pathway utilizing point-of-care (POC) testing and sonography as soon as uncomplicated renal or ureteral colic is suspected and to compare the POC clinical pathway to a standard one. METHODS: Unblinded randomized controlled clinical trial in a hospital emergency department (ED). We enrolled patients with suspected uncomplicated renal or ureteral colic and randomized them to a POC or standard pathway(1:1 ratio). Duration of ED stay, treatments, the proportion of diagnoses other than uncomplicated colic, and 30-daycomplications were analyzed. RESULTS: One hundred forty patients were recruited between November 2018 and October 2019; data for 124 were analyzed. The mean (SD) total time in the ED was 112 (45) minutes in the POC arm and 244 (102) in the standard arm (P< .001). Treatments, alternative diagnoses, and complication rates did not differ. CONCLUSION: The use of a fast-track POC pathway to manage uncomplicated colic in the ED is effective and safe. It also reduces the amount of time spent in the ED

Point-of-care characterization and risk-based management of oral lesions in primary dental clinics: A simulation model.

OBJECTIVES: Oral potentially malignant disorders (OPMDs) encompass histologically benign, dysplastic, and cancerous lesions that are often indistinguishable by appearance and inconsistently managed. We assessed the potential impact of test-and-treat pathways enabled by a point-of-care test for OPMD characterization. MATERIALS AND METHODS: We constructed a decision-analytic model to compare life expectancy of test-treat strategies for 60-year-old patients with OPMDs in the primary dental setting, based on a trial for a point-of-care cytopathology tool (POCOCT). Eight strategies of OPMD detection and evaluation were compared, involving deferred evaluation (no further characterization), prompt OPMD characterization using POCOCT measurements, or the commonly recommended usual care strategy of routine referral for scalpel biopsy. POCOCT pathways differed in threshold for additional intervention, including surgery for any dysplasia or malignancy, or for only moderate or severe dysplasia or cancer. Strategies with initial referral for biopsy also reflected varied treatment thresholds in current practice between surgery and surveillance of mild dysplasia. Sensitivity analysis was performed to assess the impact of variation in parameter values on model results. RESULTS: Requisite referral for scalpel biopsy offered the highest life expectancy of 20.92 life-years compared with deferred evaluation (+0.30 life-years), though this outcome was driven by baseline assumptions of limited patient adherence to surveillance using POCOCT. POCOCT characterization and surveillance offered only 0.02 life-years less than the most biopsy-intensive strategy, while resulting in 27% fewer biopsies. When the probability of adherence to surveillance and confirmatory biopsy was ≥ 0.88, or when metastasis rates were lower than reported, POCOCT characterization extended life-years (+0.04 life-years) than prompt specialist referral. CONCLUSION: Risk-based OPMD management through point-of-care cytology may offer a reasonable alternative to routine referral for specialist evaluation and scalpel biopsy, with far fewer biopsies. In patients who adhere to surveillance protocols, POCOCT surveillance may extend life expectancy beyond biopsy and follow up visual-tactile inspection.

Emerging Telemedicine Tools for Remote COVID-19 Diagnosis, Monitoring, and Management.

The management of the COVID-19 pandemic has relied on cautious contact tracing, quarantine, and sterilization protocols while we await a vaccine to be made widely available. Telemedicine or mobile health (mHealth) is well-positioned during this time to reduce potential disease spread and prevent overloading of the healthcare system through at-home COVID-19 screening, diagnosis, and monitoring. With the rise of mass-fabricated electronics for wearable and portable sensors, emerging telemedicine tools have been developed to address shortcomings in COVID-19 diagnostics, monitoring, and management. In this Perspective, we summarize current implementations of mHealth sensors for COVID-19, highlight recent technological advances, and provide an overview on how these tools may be utilized to better control the COVID-19 pandemic.

Logistics of an advanced therapy medicinal product during COVID-19 pandemic in Italy: successful delivery of mesenchymal stromal cells in dry ice.

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. METHODS: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. RESULTS: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes. CONCLUSIONS: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.

Do point-of-care tests (POCTs) offer a new paradigm for the management of patients with influenza?

The introduction of point-of-care tests (POCTs) has presented new opportunities for the management of patients presenting to healthcare providers with acute respiratory symptoms. This Perspective article is based on the experiences of national infection teams/those managing acute respiratory infections across the United Kingdom in terms of the challenges and opportunities that this may present for public health. This Perspective article was conceived and written pre-coronavirus disease (COVID-19), however the principles we outline here for influenza can also be translated to COVID-19 and some key points are made throughout the article. The greatest challenge for intergrating POCTs into non-traditional environments is the capture of data and samples for surveillance purposes which provides information for public health action. However, POCTs together with measures outlined in this article, offer a new paradigm for the management and public health surveillance of patients with influenza.

Implementation planning for community-based point-of-care HIV testing for infants: Recommendations from community leaders in Kenya.

BACKGROUND: Early infant diagnosis (EID) establishes the presence of HIV infection in HIV-exposed infants and children younger than 18 months of age. EID services are hospital-based, and thus fail to capture HIV-exposed infants who are not brought to the hospital for care. Point-of-care (POC) diagnostic systems deployed in the community could increase the proportion tested and linked to treatment, but little feasibility and acceptability data is available. METHODS: Semi-structured interviews (n = 74) were conducted by a Kenyan team with community members (Community Health Workers/Volunteers [CHW/CHV], Traditional Birth Attendants [TBAs], community leaders) and parents of HIV-exposed infants at four study sites in Kenya to elicit feedback on the acceptability and feasibility of community-based POC HIV testing. RESULTS: Participants described existing community health resources that could be leveraged to support integration of community-based POC HIV testing; however, the added demand placed on CHW/CHV could pose a challenge. Participants indicated that other potential barriers (concerns about confidentiality, disclosure, and HIV stigma) could be overcome with strong engagement from trusted community leaders and health providers, community sensitization, and strategic location and timing of testing. These steps were seen to improve acceptability and maximize the recognized benefits (rapid results, improved reach) of community-based testing. CONCLUSION: Community members felt that with strategic planning and engagement, community-based POC HIV testing could be a feasible and acceptable strategy to overcome the existing barriers of hospital-based EID.

Combatting COVID-19: is ultrasound an important piece in the diagnostic puzzle?

The current COVID-19 pandemic is causing diagnostic and risk stratification difficulties in Emergency Departments (ED) worldwide. Molecular tests are not sufficiently sensitive, and results are usually not available in time for decision making in the ED. Chest x-ray (CXR) is a poor diagnostic test for COVID-19, and computed tomography (CT), while sensitive, is impractical as a diagnostic test for all patients. Lung ultrasound (LUS) has an established role in the evaluation of acute respiratory failure and has been used during the COVID-19 outbreak as a decision support tool. LUS shows characteristic changes in viral pneumonitis, and while these changes are not specific for COVID-19, it may be a useful adjunct during the diagnostic process. It is quick to perform and repeat and may be done at the bedside. The authors believe that LUS can help to mitigate uncertainty in undifferentiated patients with respiratory symptoms. This review aims to provide guidance regarding indications for LUS, describe the typical sonographic abnormalities seen in patients with COVID-19 and provide recommendations around the logistics of performing LUS on patients with COVID-19 and managing the infection control risk of the procedure. The risk of anchoring bias during a pandemic and the need to consider alternative pathologies are emphasised throughout this review. LUS may be a useful point-of-care test for emergency care providers during the current COVID-19 pandemic if used within a strict framework that governs education, quality assurance and proctored scanning protocols.

Point-of-care blood gas analyzers have an impact on the acceptance of donor lungs for transplantation.

An organ donor PaO2 above 40 kPa is generally required for lung transplantation. Point-of-care (POC) blood gas analyzers are commonly used by organ procurement organizations (OPO) but may underestimate the PaO2 at high levels. We hypothesized that changing to a more accurate blood gas analyzer would result in additional lungs transplanted. All PaO2 measurements on organ donors managed at one OPO's recovery center were performed on an i-STAT POC analyzer prior to October 2015, and on a GEM 4000 subsequently. For 24 weeks, all blood gases were tested simultaneously on both analyzers. We compared lung outcomes of 147 donors in the year prior to this change (using the i-STAT) with 56 donors in the 24-week study period (using the GEM 4000 for lung allocation). When the PaO2 was above 40 kPa, the i-STAT PaO2 was 7.2 kPa lower on average than the GEM 4000. When the GEM PaO2 measured between 40 and 50 kPa, the corresponding i-STAT PaO2 value registered less than 40 kPa 25 out of 48 times (52%), with an average difference of 7.3 kPa (SD = 2.9). The rate of lungs transplanted using the GEM 4000 was 48% compared with 35% in the year prior using the i-STAT (p = .11), with equivalent recipient outcomes. The i-STAT analyzer underestimated the PaO2 above 40 kPa and changing to a more accurate PaO2 analyzer may increase lungs transplanted.

Reducing nosocomial transmission of COVID-19: implementation of a COVID-19 triage system.

Nosocomial transmission of COVID-19 puts patients with other medical problems at risk of severe illness and death. Of 662 inpatients with COVID-19 at an NHS Trust in South London, 45 (6.8%) were likely to have acquired COVID-19 in hospital. These patients had no evidence of respiratory or influenza-like illness on admission and developed symptoms, with positive SARS-CoV-2 PCR test results, more than 7 days after admission (>14 days for 38 [5.7%] patients). Forty (88.9%) of these patients had shared a ward with a confirmed COVID-19 case prior to testing positive. Implementation of a triage system combining clinical assessment with rapid SARS-CoV-2 testing facilitated cohorting so that fewer susceptible patients were exposed to COVID-19 on shared wards. With hospital service resumption alongside the possibility of future waves of COVID-19 related admissions, strategies to prevent nosocomial transmission are essential. Point-of-care diagnostics can complement clinical assessment to rapidly identify patients with COVID-19 and reduce risk of transmission within hospitals.

Peripherally Inserted Central Catheters (PICCs) at the Bedside by X-ray Technologists: A Review of Our Experience.

INTRODUCTION: Peripherally inserted central catheters, also known as PICC lines, are very common procedures for patients in the hospital who need to have long-term intravenous access, for various reasons such as antibiotics or total parenteral nutrition. At our institution, there is currently only one interventional radiology (IR) suite in our department to accommodate all IR procedures. Therefore, the bedside PICC program was introduced to help alleviate the workload in the IR suite and to improve overall patient care. Under the supervision of the hospital's interventional radiologists, trained x-ray technologists (medical radiation technologists [MRTs]) are inserting PICCs at the bedside. The purpose of this article is to describe the creation of a bedside PICC program by x-ray technologists in a hospital setting and to analyze the PICC insertions performed by MRTs over a six-year period. METHODS: In 2012, a bedside PICC insertion program was developed at our hospital, whereby two technologists would perform the procedure, using the Site-Rite® 8 Ultrasound System alongside the integrated Sherlock 3CG™ Diamond Tip Confirmation System. Training on these systems and procedural techniques, including venipuncture, sterile technique, and equipment knowledge and troubleshooting was provided for technologists. The point-of-care program was revamped in 2017 in that only one technologist would go to the bedside alone for PICC insertions. All data for the analyses were obtained from the Radiology Information System program used by our medical imaging department, called Coral RIS/PACS. RESULTS: Owing to staffing issues and inconsistent scheduling, an overview of yearly volumes of bedside PICCs performed increased from 45 in 2012 to 486 in 2018. After program changes made in 2017, these changes yielded a total volume of 382 of bedside PICCs performed, and an even more remarkable amount of 486 in 2018. For these two latter years, an evaluation of the program was carried out by analyzing how many bedside PICCs were performed successfully by the solo technologist. Overall success was achieved for both years: in 2017, 82% of the cases were performed by the technologist alone without any assistance, and likewise 89% in 2018. CONCLUSION: Since the onset of this process improvement initiative, the bedside PICC program by MRTs under the supervision of the interventional radiologists at our institution has benefited many patients and the hospital as a whole. It was apparent during the development of the program that consistent scheduling of trained and dedicated MRTs to do these bedside procedures on a regular basis improved the efficiency of the program.

Tissue engineering: from the bedside to the bench and back to the bedside.

The field of Tissue Engineering and Regenerative Medicine has evolved rapidly over the past thirty years. This review will summarize its history, current status and direction through the lens of clinical need, its progress through science in the laboratory and application back into patients. We can take pride in the fact that much effort and progress began with the surgical problems of children and that many surgeons in the pediatric surgical specialties have become pioneers and investigators in this new field of science, engineering, and medicine. Although the field has yet to fulfill its great promise, there have been several examples where a therapy has progressed from the first idea to human application within a short span of time and, in many cases, it has been applied in the surgical care of children.