Personalized Reminders for Immunization Using Short Messaging Systems to Improve Human Papillomavirus Vaccination Series Completion: Parallel-Group Randomized Trial

Background Completion rates among adolescents who initiate the human papillomavirus (HPV) vaccine 3-dose series are low. SMS text message vaccine reminders are effective, but less is known about the best types for HPV series completion or the ability to assess and target vaccine decision-making stage. Objective The aim of this study is to compare the effectiveness of HPV vaccine series completion in minority adolescents who received precision and educational versus conventional SMS text message reminders. Methods Enrolled parents of adolescents aged 9-17 years who received the first HPV vaccine dose at 1 of the 4 academic-affiliated community health clinics in New York City were randomized 1:1 to 1 of the 2 parallel, unblinded arms: precision SMS text messages (which included stage-targeted educational information, next dose due date, and site-specific walk-in hours) or conventional SMS text messages without educational information. Randomization was stratified according to gender, age, and language. The primary outcome was series completion within 12 months. In post hoc analysis, enrollees were compared with concurrent nonenrollees and historical controls. Results Overall, 956 parents were enrolled in the study. The precision (475 families) and conventional (481 families) SMS text message arms had similarly high series completion rates (344/475, 72.4% vs 364/481, 75.7%). A total of 42 days after the first dose, two-thirds of families, not initially in the preparation stage, moved to preparation or vaccinated stage. Those in either SMS text message arm had significantly higher completion rates than nonenrollees (708/1503, 47.1% vs 679/1503, 45.17%; P<.001). Even after removing those needing only 2 HPV doses, adolescents receiving any SMS text messages had higher completion rates than historical controls (337/2823, 11.93% vs 981/2823, 34.75%; P<.001). A population-wide effect was seen from 2014 to 2016, above historical trends. Conclusions SMS text message reminders led to timely HPV vaccine series completion in a low-income, urban, minority study population and also led to population-wide effects. Educational information did not provide an added benefit to this population. Trial Registration ClinicalTrials.gov NCT02236273; https://clinicaltrials.gov/ct2/show/NCT02236273

Proficiency-based progression intern training to reduce critical blood sampling errors including ‘wrong blood in tube’

Background: Blood sampling errors including ‘wrong blood in tube’ (WBIT) may have adverse effects on clinical outcomes. WBIT errors occur when the blood sample in the tube is not that of the patient identified on the label. This study aims to determine the effect of proficiency-based progression (PBP) training in phlebotomy on the rate of blood sampling errors (including WBIT). Methods: A non-randomised controlled trial compared the blood sampling error rate of 43 historical controls who had not undergone PBP training in 2016 to 44 PBP trained interventional groups in 2017. In 2018, the PBP training programme was implemented and the blood sampling error rate of 46 interns was compared to the 43 historical controls in 2016. Data analysis was performed using logistic regression analysis adjusting for sample timing. Results: In 2016, 43 interns had a total blood sample error rate of 2.4%, compared to 44 interns in 2017, who had error rate of 1.2% (adjusted OR=0.50, 95% CI 0.36-0.70; <0.01). In 2018, 46 interns had an error rate of 1.9% (adjusted OR=0.89, 95% CI 0.65-1.21; p=0.46) when compared to the 2016 historical controls. There were three WBITs in 2016, three WBITs in 2017 and five WBITs in 2018. Conclusions: The study demonstrates that PBP training in phlebotomy has the potential to reduce blood sampling errors. Trial registration number: NCT03577561

Ghost in the machine or monkey with a typewriter—generating titles for Christmas research articles in The BMJ using artificial intelligence: observational study

ObjectiveTo determine whether artificial intelligence (AI) can generate plausible and engaging titles for potential Christmas research articles in The BMJ.DesignObservational study.SettingEurope, Australia, and Africa.Participants1 AI technology (Generative Pre-trained Transformer 3, GPT-3) and 25 humans.Main outcome measuresPlausibility, attractiveness, enjoyability, and educational value of titles for potential Christmas research articles in The BMJ generated by GPT-3 compared with historical controls.ResultsAI generated titles were rated at least as enjoyable (159/250 responses (64%) v 346/500 responses (69%); odds ratio 0.9, 95% confidence interval 0.7 to 1.2) and attractive (176/250 (70%) v 342/500 (68%); 1.1, 0.8 to 1.4) as real control titles, although the real titles were rated as more plausible (182/250 (73%) v 238/500 (48%); 3.1, 2.3 to 4.1). The AI generated titles overall were rated as having less scientific or educational merit than the real controls (146/250 (58%) v 193/500 (39%); 2.0, 1.5 to 2.6); this difference, however, became non-significant when humans curated the AI output (146/250 (58%) v 123/250 (49%); 1.3, 1.0 to 1.8). Of the AI generated titles, the most plausible was “The association between belief in conspiracy theories and the willingness to receive vaccinations,” and the highest rated was “The effects of free gourmet coffee on emergency department waiting times: an observational study.”ConclusionsAI can generate plausible, entertaining, and scientifically interesting titles for potential Christmas research articles in The BMJ; as in other areas of medicine, performance was enhanced by human intervention.

Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia

Background: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. Methods: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. Results: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7–4.6) in the PDT group and 5.5 (3.4–7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. Conclusions: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

COVID-19 and Venous Thromboembolism: From Pathological Mechanisms to Clinical Management

Coronavirus disease 2019 (COVID-19), which is becoming a global pandemic, is caused by SARS-CoV-2 infection. In COVID-19, thrombotic events occur frequently, mainly venous thromboembolism (VTE), which is closely related to disease severity and clinical prognosis. Compared with historical controls, the occurrence of VTE in hospitalized and critical COVID-19 patients is incredibly high. However, the pathophysiology of thrombosis and the best strategies for thrombosis prevention in COVID-19 remain unclear, thus needing further exploration. Virchow’s triad elements have been proposed as important risk factors for thrombotic diseases. Therefore, the three factors outlined by Virchow can also be applied to the formation of venous thrombosis in the COVID-19 setting. A thorough understanding of the complex interactions in these processes is important in the search for effective treatments for COVID-19. In this work, we focus on the pathological mechanisms of VTE in COVID-19 from the aspects of endothelial dysfunction, hypercoagulability, abnormal blood flow. We also discuss the treatment of VTE as well as the ongoing clinical trials of heparin anticoagulant therapy. In addition, according to the pathophysiological mechanism of COVID-19-associated thrombosis, we extended the range of antithrombotic drugs including antiplatelet drugs, antifibrinolytic drugs, and anti-inflammatory drugs, hoping to find effective drug therapy and improve the prognosis of VTE in COVID-19 patients.

Neonatal Outcomes of Premature Infants Born to Women with the Novel Coronavirus (SARS-CoV-2) Infection: A Case Control Study

Objective Novel coronavirus disease 2019 (COVID-19) is a disease associated with atypical pneumonia caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The first cases of COVID-19 were reported in Wuhan at the end of 2019. Transmission usually occurs via infected droplets and close personal contact; the possibility of vertical transmission is still under debate. This retrospective study aimed to analyze clinical characteristics of premature infants born to mothers with symptomatic COVID-19 disease. Study Design This case control study compared the clinical and laboratory data of 20 premature infants born to mothers infected with SARS-CoV-2 with sex and gestational age–matched historical controls. Results The median gestational age and birth weight in both groups were similar. Respiratory distress developed in 11 (55.5%) infants in study group and 19 (47.5%) infants in control group. Mechanical ventilation and endotracheal surfactant administration rates were similar. Median duration of hospitalization was 8.5 (2–76) days in study group and 12 days in historical controls. Real-time reverse-transcription polymerase chain reaction tests (RT-PCR) of nasopharyngeal swab samples for SARS-CoV-2 were found to be negative twice, in the first 24 hours and later at 24 to 48 hours of life. No neutropenia or thrombocytopenia was detected in the study group. Patent ductus arteriosus, bronchopulmonary dysplasia, and necrotizing enterocolitis rates were similar between groups. No mortality was observed in both groups. Conclusion To the best of our knowledge, this is one of the few studies evaluating the clinical outcomes of premature infants born to SARS-CoV-2 infected mothers. There was no evidence of vertical transmission of SARS-CoV-2 from symptomatic SARS-CoV-2-infected women to the neonate in our cohort. The neonatal outcomes also seem to be favorable with no mortality in preterm infants. Key Points

Abstract 10618: A Head up CPR Based Care Bundle Improves the Likelihood of Survival to Hospital Discharge After Out of Hospital Cardiac Arrest

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain poor with widespread use of conventional (C) CPR. Based on pre-clinical studies showing improved cerebral flow and neurologically-intact survival, a FDA approved automated Head Up Positioning (AHUP) device for CPR was developed for use with an impedance threshold device (ITD), and manual and/or automated suction cup-based CPR. A prospective observational IRB approved registry was created to track use and clinical outcomes with this AHUP device based bundle. Hypothesis: Faster time to use of an AHUP CPR bundle improves survival to hospital discharge after OHCA versus historical controls treated with C-CPR. Methods: Registry patients from sites routinely recording time from 911 call to AHUP device placement (T 911 ) were included. C-CPR controls were from 3 prior randomized prospective CPR trials: 1) Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) Study, 2) Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study (ROC-ALPS), 3) The ResQTrial. Propensity score analysis was performed using logistic regression for baseline characteristics including age, sex, witnessed arrest, bystander CPR, shockable rhythm, and time to first responder CPR. Each AHUP patient was matched with up to 4 C-CPR patients. Results: Of 11 U.S. sites reporting AHUP CPR outcomes, 6 had time from 911 call to AHUP device placement recorded (n = 227). The model yielded a c-statistic of 0.76. Stratified by T 911 , the odds of survival with AHUP CPR were significantly higher than with C-CPR between T 911 < 7 minutes (OR 4.57, 95% CI 1.3-16.0) and T 911 < 15 minutes (OR 2.01, 95% CI 1.1-3.8). There was a time dependent effect of AHUP device placement on survival (See Figure). Conclusions: More rapid initiation of an AHUP CPR bundle resulted in improved survival to hospital discharge versus historical controls treated with C-CPR in OHCA.

A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma

Background The blood brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability. Methods Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged. Results The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p &lt; 0.001) and LITT with standard salvage therapy (p &lt; 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well-tolerated with comparable adverse event rates between the arms. Conclusions Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.