Publications by authors named "Kevin Kelly"

378 Publications

Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.

medRxiv 2021 Oct 7. Epub 2021 Oct 7.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Delta's infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average ∼6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Delta's enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations.
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http://dx.doi.org/10.1101/2021.10.06.21264641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509091PMC
October 2021

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

Intern Emerg Med 2021 Oct 12. Epub 2021 Oct 12.

Department of Endocrinology, Ashford and St Peter's Hospitals NHS Foundation Trust, Guildford Road, Chertsey, Surrey, KT16 0PZ, UK.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI). Among 12,471 admissions, 1452 (11.6%) patients were diagnosed with COVID-19. On admission, the mean (± SD) age of patients with other causes was 68.3 years (± 19.8) and those with COVID-19 in wave 1 was 69.4 years (± 18.0) and wave 2 was 66.2 years (± 18.4). Corresponding ages at discharge were 67.5 years (± 19.7), 63.9 years (± 18.0) and 62.4 years (± 18.0). The highest proportion of total admissions was among the oldest group (≥ 80 years) in wave 1 (35.0%). When compared with patients admitted with other causes, those admitted with COVID-19 in wave 1 and in wave 2 were more frequent in the 40-59 year band: 20.8, 24.6 and 30.0%; consisted of more male patients: 47.5, 57.6 and 58.8%; and a high LACE (Length of stay, Acuity of admission, Comorbidity and Emergency department visits) index (score ≥ 10): 39.4, 61.3 and 50.3%. Compared to wave-2 patients, those admitted in wave 1 had greater risk of death in hospital: OR = 1.58 (1.18-2.12) and within 30 days of discharge: OR = 2.91 (1.40-6.04). Survivors of COVID-19 in wave 1 stayed longer in hospital (median = 6.5 days; interquartile range = 2.9-12.0) as compared to survivors from wave 2 (4.5 days; interquartile range = 1.9-8.7). Patient characteristics differed significantly between the two waves of COVID-19 pandemic. There was an improvement in outcomes in wave 2, including shorter length of stay in hospital and reduction of mortality.
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http://dx.doi.org/10.1007/s11739-021-02842-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505475PMC
October 2021

Infrared object classification with a hybrid optical convolution neural network.

Appl Opt 2021 Sep;60(25):G224-G231

Recent advancements in machine vision have enabled a great range of applications from image classification to autonomous driving. However, there is still a dilemma between the pursuit of higher-resolution training images that require a detector array with more pixels on the front end, and the demands on acquisition for embedded systems restrained by power, transmission bandwidth, and storage. In this paper, a multi-pixel hybrid optical convolutional neural network machine vision system was designed and validated to perform high-speed infrared object detection. The proposed system replicates the front convolution layer in a convolutional neural network utilizing a high-speed digital micro-mirror device to display the first layer of kernels at a resolution greater than the subsequent detector. After this, further convolutions are carried out in software to perform the object recognition. An infrared vehicle dataset was used to validate the performance of the hybrid system through simulation. We also tested this in hardware by performing infrared classification on toy vehicles to showcase the feasibility of such a design.
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http://dx.doi.org/10.1364/AO.427973DOI Listing
September 2021

General neural network approach to compressive feature extraction.

Appl Opt 2021 Sep;60(25):G217-G223

Computer vision with a single-pixel camera is currently limited by a trade-off between reconstruction capability and image classification accuracy. If random projections are used to sample the scene, then reconstruction is possible but classification accuracy suffers, especially in cases with significant background signal. If data-driven projections are used, then classification accuracy improves and the effect of the background is diminished, but image recovery is not possible. Here, we employ a shallow neural network to nonlinearly convert from measurements acquired with random patterns to measurements acquired with data-driven patterns. The results demonstrate that this improves classification accuracy while still allowing for full reconstruction.
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http://dx.doi.org/10.1364/AO.427383DOI Listing
September 2021

Time-optimized feeding is beneficial without enforced fasting.

Open Biol 2021 Oct 6;11(10):210183. Epub 2021 Oct 6.

Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.

Time-restricted feeding (TRF) studies underscore that food is consumed during the daily cycle is important for weight gain/loss because the circadian clock rhythmically modulates metabolism. However, the interpretation of previous TRF studies has been confounded by study designs that introduced an extended period of enforced fasting. We introduce a novel time-optimized feeding (TOF) regimen that disentangles the effects of phase-dependent feeding from the effects of enforced fasting in mice, as well as providing a laboratory feeding protocol that more closely reflects the eating patterns of humans who usually have 24 hour access to food. Moreover, we test whether a sudden switch from ad libitum food access to TRF evokes a corticosterone (stress) response. Our data indicate that the timing of high-fat feeding under TOF allows most of the benefit of TRF without obligatory fasting or evoking a stress response. This benefit occurs through stable temporal coupling of carbohydrate/lipid oxidation with feeding. These results highlight that timing the ingestion of calorically dense foods to optimized daily phases will enhance lipid oxidation and thereby limit fat accumulation.
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http://dx.doi.org/10.1098/rsob.210183DOI Listing
October 2021

The Prevalence of Fibromyalgia Syndrome in Active Duty Military Personnel.

Arthritis Care Res (Hoboken) 2021 Oct 4. Epub 2021 Oct 4.

University of Texas Health Science Center at San Antonio.

Objective: Previous research with civilian populations has found strong associations between fibromyalgia (FM) and posttraumatic stress disorder (PTSD). This study is the first large-scale investigation of the prevalence of FM in military service members with and without PTSD.

Methods: Participants were active duty military recruited into either an epidemiological cohort study of service members prior to a military deployment or 1 of 3 PTSD treatment trials. Instruments used to document FM and PTSD included the PTSD Checklist - Stressor-Specific Version (PCL-S), the PTSD Symptom Scale-Interview (PSS-I), and the 2012 American College of Rheumatology fibromyalgia questionnaire.

Results: Across the 4 studies, 4,376 subjects completed surveys. The prevalence of FM was 2.9% in the predeployment cohort and the prevalence was significantly higher in individuals with PTSD (10.8%) compared to those without PTSD (0.8%). In the treatment trials, all of the participants met criteria for PTSD prior to starting treatment and the prevalence of FM was 39.7%.

Conclusion: The prevalence of FM in active duty service members preparing to deploy is similar to that reported for the general population of the U.S., but higher than expected for a predominantly male cohort. Furthermore, the prevalence of FM was significantly higher in service members with comorbid PTSD and highest among those seeking treatment for PTSD. Further investigation is needed to determine the factors linking PTSD and FM.
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http://dx.doi.org/10.1002/acr.24801DOI Listing
October 2021

STRONG STAR and the Consortium to Alleviate PTSD: Shaping the future of combat PTSD and related conditions in military and veteran populations.

Contemp Clin Trials 2021 Sep 29;110:106583. Epub 2021 Sep 29.

VA VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA; Central Texas Veterans Health Care System, Temple, TX, USA. Electronic address:

The STRONG STAR Consortium (South Texas Research Organizational Network Guiding Studies on Trauma and Resilience) and the Consortium to Alleviate PTSD are interdisciplinary and multi-institutional research consortia focused on the detection, diagnosis, prevention, and treatment of combat-related posttraumatic stress disorder (PTSD) and comorbid conditions in military personnel and veterans. This manuscript outlines the consortia's state-of-the-science collaborative research model and how this can be used as a roadmap for future trauma-related research. STRONG STAR was initially funded for 5 years in 2008 by the U.S. Department of Defense's (DoD) Psychological Health and Traumatic Brain Injury Research Program. Since the initial funding of STRONG STAR, almost 50 additional peer-reviewed STRONG STAR-affiliated projects have been funded through the DoD, the U.S. Department of Veterans Affairs (VA), the National Institutes of Health, and private organizations. In 2013, STRONG STAR investigators partnered with the VA's National Center for PTSD and were selected for joint DoD/VA funding to establish the Consortium to Alleviate PTSD. STRONG STAR and the Consortium to Alleviate PTSD have assembled a critical mass of investigators and institutions with the synergy required to make major scientific and public health advances in the prevention and treatment of combat PTSD and related conditions. This manuscript provides an overview of the establishment of these two research consortia, including their history, vision, mission, goals, and accomplishments. Comprehensive tables provide descriptions of over 70 projects supported by the consortia. Examples are provided of collaborations among over 50 worldwide academic research institutions and over 150 investigators.
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http://dx.doi.org/10.1016/j.cct.2021.106583DOI Listing
September 2021

Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study.

Lancet Haematol 2021 Sep 13. Epub 2021 Sep 13.

Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138 and synergistically enhances the antitumor activity of lenalidomide in preclinical models of multiple myeloma. This phase 1/2a study was done to determine the safety, activity, and pharmacokinetics of indatuximab ravtansine in combination with immunomodulatory drugs in patients with relapsed or refractory multiple myeloma.

Methods: This open-label, phase 1/2a study took place at nine hospital sites in the USA. Eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and ECOG performance status or Zubrod score of 2 or below. Patients who received indatuximab ravtansine with lenalidomide and dexamethasone (indatuximab ravtansine plus lenalidomide) had failure of at least one previous therapy. Patients treated with indatuximab ravtansine with pomalidomide and dexamethasone (indatuximab ravtansine plus pomalidomide) had failure of at least two previous therapies (including lenalidomide and bortezomib) and had progressive disease on or within 60 days of completion of their last treatment. In phase 1, patients received indatuximab ravtansine intravenously on days 1, 8, and 15 of each 28-day cycle in escalating dose levels of 80 mg/m, 100 mg/m, and 120 mg/m, with lenalidomide (25 mg; days 1 to 21 every 28 days orally) and dexamethasone (20-40 mg; days 1, 8, 15, and 22 every 28 days). In phase 2, the recommended phase 2 dose of indatuximab ravtansine was given to an expanded cohort of patients in combination with lenalidomide and dexamethasone. The protocol was amended to allow additional patients to be treated with indatuximab ravtansine plus pomalidomide (4 mg; days 1 to 21 every 28 days orally) and dexamethasone, in a more heavily pretreated patient population than in the indatuximab ravtansine plus lenalidomide group. The phase 1 primary endpoint was to determine the dose-limiting toxicities and the maximum tolerated dose (recommended phase 2 dose) of indatuximab ravtansine, and the phase 2 primary endpoint was to describe the objective response rate (ORR; partial response or better) and clinical benefit response (ORR plus minor response). All patients were analysed for safety and all patients with post-treatment response assessments were analysed for activity. This study is registered with ClinicalTrials.gov, number NCT01638936, and is complete.

Findings: 64 (86%) of 74 screened patients were enrolled between July 3, 2012, and June 30, 2015. 47 (73%) patients received indatuximab ravtansine plus lenalidomide (median follow-up 24·2 months [IQR 19·9-45·4]) and 17 (27%) received indatuximab ravtansine plus pomalidomide (24·1 months [17·7-36·7]). The maximum tolerated dose of indatuximab ravtansine plus lenalidomide was 100 mg/m, and defined as the recommended phase 2 dose for indatuximab ravtansine plus pomalidomide. An objective response for indatuximab ravtansine plus lenalidomide was observed in 33 (71·7%) of 46 patients and in 12 (70·6%) of 17 patients in the indatuximab ravtansine plus pomalidomide group. The clinical benefit response for indatuximab ravtansine plus lenalidomide was 85% (39 of 46 patients) and for indatuximab ravtansine plus pomalidomide it was 88% (15 of 17 patients). The most common grade 3-4 adverse events in both groups were neutropenia (14 [22%] of 64 patients), anaemia (10 [16%]), and thrombocytopenia (seven [11%]). Treatment-emergent adverse events (TEAEs) that led to discontinuation occurred in 35 (55%) of the 64 patients. Five (8%) patients with a TEAE had a fatal outcome; none was reported as related to indatuximab ravtansine.

Interpretation: Indatuximab ravtansine in combination with immunomodulatory drugs shows preliminary antitumor activity, is tolerated, and could be further evaluated in patients with relapsed or refractory multiple myeloma.

Funding: Biotest AG.
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http://dx.doi.org/10.1016/S2352-3026(21)00208-8DOI Listing
September 2021

Update on latex allergy: New insights into an old problem.

World Allergy Organ J 2021 Aug 28;14(8):100569. Epub 2021 Jul 28.

InAER -Investigaciones en Enfermedades Alérgicas y Respiratorias, Buenos Aires, Argentina.

Despite the efforts made to mitigate the consequences of this disease, natural rubber latex allergy (NRLA) continues to be a global health problem and is still considered one of the main worries in the working environment in many countries throughout the world. Due to thousands of products containing latex, it is not surprising that the current statistics suggest that prevalence remains high among healthcare workers and susceptible patients. In developed countries, reduction in the prevalence of IgE-mediated allergy to latex proteins from gloves may lead to lax attention by health care personnel. On the other hand, this situation is different in developing countries where there is a lack of epidemiological data associated with a deficit in education and awareness of this issue. The aim of this review is to provide an update of the current knowledge and practical recommendations regarding NRLA by allergologists from different parts of the world with experience in this field.
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http://dx.doi.org/10.1016/j.waojou.2021.100569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335653PMC
August 2021

Intimate Relationship between Sterile Neutrino Dark Matter and ΔN_{eff}.

Phys Rev Lett 2021 Jul;127(4):041101

Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6, Canada.

The self-interacting neutrino hypothesis is well motivated for addressing the tension between the origin of sterile neutrino dark matter and indirect detection constraints. It can also result in a number of testable signals from the laboratories to the cosmos. We show that, in a broad class of models, where the sterile neutrino dark matter relic density is generated by a light neutrinophilic mediator, there must be a lower bound on the amount of extra radiation in early Universe, in particular, ΔN_{eff}>0.12 at the cosmic microwave background (CMB) epoch. This lower bound will be further strengthened with an improved x-ray search at the Athena observatory. Such an intimate relationship will be unambiguously tested by the upcoming CMB Stage 4 project.
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http://dx.doi.org/10.1103/PhysRevLett.127.041101DOI Listing
July 2021

Fimepinostat (CUDC-907) in patients with relapsed/refractory diffuse large B cell and high-grade B-cell lymphoma: report of a phase 2 trial and exploratory biomarker analyses.

Br J Haematol 2021 Oct 2;195(2):201-209. Epub 2021 Aug 2.

MD Anderson Cancer Center, Houston, TX, USA.

Fimepinostat (CUDC-907), a first-in-class oral small-molecule inhibitor of histone deacetylase and phosphatidylinositol 3-kinase, demonstrated efficacy in a phase 1 study of patients with relapsed/refractory (R/R) diffuse large and high-grade B-cell lymphomas (DLBCL/HGBL), particularly those with increased MYC protein expression and/or MYC gene rearrangement/copy number gain (MYC-altered disease). Therefore, a phase 2 study of fimepinostat was conducted in this patient population with 66 eligible patients treated. The primary end-point of overall response (OR) rate for patients with MYC-IHC ≥40% (n = 46) was 15%. Subsequently, exploratory pooled analyses were performed including patients treated on both the phase 1 and 2 studies based upon the presence of MYC-altered disease as well as a biomarker identified by Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER). For these patients with MYC-altered disease (n = 63), the overall response (OR) rate was 22% with seven responding patients remaining on treatment for approximately two years or longer, and VIPER yielded a three-protein biomarker classification with positive and negative predictive values of ≥85%. Prolonged durations of response were achieved by patients with MYC-altered R/R DLBCL/HGBL treated with single-agent fimepinostat. Combination therapies and/or biomarker-based patient selection strategies may lead to higher response rates in future clinical trials.
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http://dx.doi.org/10.1111/bjh.17730DOI Listing
October 2021

In response to Lemke: Where you see a forest, I just see detritus.

Authors:
Kevin M Kelly

J Occup Environ Med 2021 Jul 30. Epub 2021 Jul 30.

Department of Anthropology, Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, 52242 U.S.A.

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http://dx.doi.org/10.1097/JOM.0000000000002342DOI Listing
July 2021

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 lineages.

medRxiv 2021 Jul 2. Epub 2021 Jul 2.

Emerging SARS-CoV-2 variants have shaped the second year of the COVID-19 pandemic and the public health discourse around effective control measures. Evaluating the public health threat posed by a new variant is essential for appropriately adapting response efforts when community transmission is detected. However, this assessment requires that a true comparison can be made between the new variant and its predecessors because factors other than the virus genotype may influence spread and transmission. In this study, we develop a framework that integrates genomic surveillance data to estimate the relative effective reproduction number (R ) of co-circulating lineages. We use Connecticut, a state in the northeastern United States in which the SARS-CoV-2 variants B.1.1.7 and B.1.526 co-circulated in early 2021, as a case study for implementing this framework. We find that the R of B.1.1.7 was 6-10% larger than that of B.1.526 in Connecticut in the midst of a COVID-19 vaccination campaign. To assess the generalizability of this framework, we apply it to genomic surveillance data from New York City and observe the same trend. Finally, we use discrete phylogeography to demonstrate that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of B.1.1.7 were larger than those resulting from B.1.526 introductions. Our framework, which uses open-source methods requiring minimal computational resources, may be used to monitor near real-time variant dynamics in a myriad of settings.
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http://dx.doi.org/10.1101/2021.07.01.21259859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259915PMC
July 2021

Relation of Intravascular Volume Profiles to Heart Failure Progression and Clinical Outcomes.

Am J Cardiol 2021 08 29;153:65-70. Epub 2021 Jun 29.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Heart failure (HF) commonly progresses over time and identifying differences in volume profiles may help stratify risk and guide therapy. The aim of this study was to assess the pathophysiologic and prognostic roles of volume profiles for HF progression in stable ambulatory and hospitalized patients. HF patients who had undergone quantitative intravascular volume analysis (185 outpatients and 139 inpatients) were retrospectively assessed for the combined end point of HF-related hospital admissions (outpatients), HF-readmissions (inpatients), and overall all-cause mortality. After multivariate Cox regression analysis, greater total blood volume expansion was associated with higher risk of HF-admission in previously stable outpatients (HR: 1.023, CI 1.005 to 1.043; p = 0.013) while in more advanced HF (inpatients) total blood volume expansion was associated with lower risk for HF-readmission and mortality (HR: 0.982, CI 0.967 to 0.997; p = 0.017). Secondary analysis suggests that subclinical plasma volume expansion was a driving factor for the detrimental association in outpatients (HR: 1.018, CI 0.997 to 1.036; p = 0.054), while an increase in red blood cell mass was central to the beneficial association in advanced HF (HR: 0.979, CI 0.968 to 0.991; p <0.001). In conclusion, understanding differences in plasma volume and red blood cell mass profiles can provide insight into the pathophysiology and progression of HF.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316305PMC
August 2021

Resorbable Versus Titanium Hardware for Rigid Fixation of Pediatric Upper and Midfacial Fractures: Which Carries a Lower Risk Profile?

J Oral Maxillofac Surg 2021 10 25;79(10):2103-2114. Epub 2021 May 25.

Chief, Division of Pediatric Plastic Surgery, Division of Cleft and Craniofacial Surgery, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN.

Purpose: Titanium associated risks have led to interest in resorbable hardware for open reduction and internal fixation (ORIF) of pediatric facial fractures. This study aims to systematically review and compare the outcomes of titanium/resorbable hardware used for ORIF of upper/midfacial fractures to determine which hardware carries a higher complication rate in the pediatric patient.

Methods: Studies published between 1990 and 2020 on the ORIF of pediatric upper/midfacial fractures were systematically reviewed. A retrospective institutional review was also conducted, and both arms were compiled for final analysis. The primary predictor value was the type of hardware used and the primary outcome was the presence of a complication. Fisher's exact test and 2-proportion 2-tailed z-test calculations were used to determine statistical significance, which was defined as a P value < .05. The low quality of published evidence precluded meta-analysis.

Results: Systematic review of 23 studies identified 659 patients, and 77 patients were identified in the institutional review. A total of 736 patients (299 resorbable, 437 titanium) were included in the final analysis. Total complication rate was 22.8%. The titanium group had a higher complication rate (27 vs 16.7%; P < .01), and more often underwent elective hardware removal (87.3 vs 0%, P < .01). In each hardware subgroup, the incidence of complications was analyzed by fracture site. In the titanium group, complication incidence was higher when treating maxillary fractures (32.8 vs 22.9%, P = .03). When comparing the 2 hardware groups by fracture site, maxillary fractures had a higher rate of complications when treated by titanium hardware compared with resorbable hardware (32.8 vs 18%, P < .01).

Conclusions: Upper/midfacial pediatric fractures requiring ORIF, especially maxillary fractures, may be best treated with resorbable hardware. Additional hardware-specific outcomes data is encouraged.
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http://dx.doi.org/10.1016/j.joms.2021.05.027DOI Listing
October 2021

Critical Points in Lemke's Total Worker Health Calculus.

J Occup Environ Med 2021 Jun 16. Epub 2021 Jun 16.

Deputy Director, Healthier Workforce Center of the Midwest, Associate Research Scientist, Department of Occupational and Environmental Health, Adjunct Associate Professor of Anthropology, University of Iowa, Iowa City, IA Center Director, Center for Health, Work & Environment, Distinguished University Professor, Colorado School of Public Health, CU Anschutz Medical Campus, Aurora, CO Co-Director, Center for the Promotion of Health in the New England Workplace (CPH-NEW), Professor of Medicine, UConn Health, Farmington, CT Co-Director, Center for the Promotion of Health in the New England Workplace (CPH-NEW), Professor of Epidemiology and Occupational Ergonomics, University of Massachusetts Lowell, Lowell, MA Co-Director, Oregon Healthy Workforce Center, Professor, Oregon Institute of Occupational Health Sciences, Oregon Health & Science University; Professor of Psychology, Portland State University, Portland, OR Director, Harvard Chan School Center for Work, Health and Wellbeing, Professor of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA.

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http://dx.doi.org/10.1097/JOM.0000000000002300DOI Listing
June 2021

Reduction in massive postpartum haemorrhage and red blood cell transfusion during a national quality improvement project, Obstetric Bleeding Strategy for Wales, OBS Cymru: an observational study.

BMC Pregnancy Childbirth 2021 May 15;21(1):377. Epub 2021 May 15.

Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion.

Methods: A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data.

Results: Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment.

Conclusions: The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.
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http://dx.doi.org/10.1186/s12884-021-03853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126150PMC
May 2021

Reduction in massive postpartum haemorrhage and red blood cell transfusion during a national quality improvement project, Obstetric Bleeding Strategy for Wales, OBS Cymru: an observational study.

BMC Pregnancy Childbirth 2021 May 15;21(1):377. Epub 2021 May 15.

Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion.

Methods: A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data.

Results: Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment.

Conclusions: The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.
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http://dx.doi.org/10.1186/s12884-021-03853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126150PMC
May 2021

Murine double minute 2 inhibition alone or with cytarabine in acute myeloid leukemia: Results from an idasanutlin phase 1/1b study⋆.

Leuk Res 2021 01 1;100:106489. Epub 2020 Dec 1.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy.

The prognosis remains poor for patients with relapsed or refractory (r/r) acute myeloid leukemia; thus, novel therapies are needed. We evaluated idasanutlin-a new, potent murine double minute 2 antagonist-alone or with cytarabine in patients with r/r acute myeloid leukemia, de novo untreated acute myeloid leukemia unsuitable for standard treatment or with adverse features, or secondary acute myeloid leukemia in a multicenter, open-label, phase 1/1b trial. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) and characterize the safety profile of idasanutlin monotherapy and combination therapy. Clinical activity and pharmacokinetics were secondary objectives. Two idasanutlin formulations were investigated: a microprecipitate bulk powder (MBP) and optimized spray-dried powder (SDP). Following dose escalation, patients (N = 122) received idasanutlin at the RDE in the extension cohorts. No formal MTD was identified. Idasanutlin was tolerable alone and in combination with cytarabine. The RDE was determined as 600 mg twice a day for the MBP formulation and 300 mg twice a day for the SDP formulation. Adverse events were mostly grade 1/2 (76.2 %). The most common any-grade adverse events were gastrointestinal (including diarrhea [90.2 %]). The early death rate across all patients was 14.8 %. Plasma idasanutlin exposure was dose related. In TP53 wild-type patients, composite complete remission rates were 18.9 % with monotherapy and 35.6 % with combination therapy. Based on these results, idasanutlin development continued with further investigation in the treatment of acute myeloid leukemia. ClinicalTrials.gov: NCT01773408.
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http://dx.doi.org/10.1016/j.leukres.2020.106489DOI Listing
January 2021

Spectroscopic imaging of surfaces-Sum frequency generation microscopy (SFGM) combined with compressive sensing (CS) technique.

J Chem Phys 2020 Nov;153(19):190901

Department of Chemistry, University of Houston, Houston, Texas 77204-5003, USA.

Surface chemistry is notoriously difficult to study, in part, due to the decreased number of molecules that contribute to the properties compared to the bulk phase but often has significant effects on the chemical activity of the material. This is especially true in topics such as corrosion, catalysis, wetting, and many others in nature and industry. Sum frequency generation (SFG) spectroscopy was developed for interface studies due to its high molecular selectivity and surface sensitivity, which is quite useful to study the effects of structural inhomogeneity in microscopy. Compressive sensing (CS) combined with SFG spectroscopy minimizes the imaging time while still producing quality images. Selected systems are presented here to demonstrate the capability of CS-SFG microscopy. CS-SFG microscopy successfully distinguished the static monolayer molecular mixtures, the orientations and adsorption of adsorbed molecules by the dip-coating technique, and the localized CO behaviors on polycrystalline Pt electrodes. Further discussion includes dynamic imaging as a future direction in CS-SFG microscopy. As materials and surfaces become more complex, imaging with chemical contrast becomes indispensable to understanding their performance and CS-SFG microscopy seems highly beneficial in this respect.
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http://dx.doi.org/10.1063/5.0022691DOI Listing
November 2020

A hyperspectral projector for simultaneous 3D spatial and hyperspectral imaging via structured illumination.

Opt Express 2020 Sep;28(20):29740-29755

Both 3D imaging and hyperspectral imaging provide important information of the scene and combining them is beneficial in helping us perceive and understand real-world structures. Previous hyperspectral 3D imaging systems typically require a hyperspectral imaging system as the detector suffers from complicated hardware design, high cost, and high acquisition and reconstruction time. Here, we report a low-cost, high-frame rate, simple-design, and compact hyperspectral stripe projector (HSP) system based on a single digital micro-mirror device, capable of producing hyperspectral patterns where each row of pixels has an independently programmable spectrum. We demonstrate two example applications using the HSP via hyperspectral structured illumination: hyperspectral 3D surface imaging and spectrum-dependent hyperspectral compressive imaging of volume density of participating medium. The hyperspectral patterns simultaneously encode the 3D spatial and spectral information of the target, requiring only a grayscale sensor as the detector. The reported HSP and its applications provide a solution for combining structured illumination techniques with hyperspectral imaging in a simple, efficient, and low-cost manner. The work presented here represents a novel structured illumination technique that provides the basis and inspiration of future variations of hardware systems and software encoding schemes.
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http://dx.doi.org/10.1364/OE.402812DOI Listing
September 2020

Degree requirements of physiology undergraduate programs in the Physiology Majors Interest Group.

Adv Physiol Educ 2020 Dec;44(4):613-619

Center for Clinical and Translational Sciences, Mayo Clinic, Rochester, Minnesota.

Physiology undergraduate degree programs operate in isolation relative to other biological science programs, with little to no understanding of how other institutions structure their course requirements and other degree requirements. The purpose of this report is to preliminarily describe the collective curriculum of physiology programs represented at the Physiology Majors Interest Group (P-MIG) annual meetings from 2018 to 2019. A short preconference survey was sent to attendees that inquired about degree requirements of their respective physiology programs. The requirement for Physiology I (69.2%) with laboratory (66.7%) and Anatomy I (57.1%) with laboratory (42.9%), or combined Anatomy and Physiology I (16.7%) and laboratory (18.2%), were common requirements, but many programs did not require Physiology II (27.3%) or Anatomy II (11.1%). There was nearly consensus on required prerequisites such as Biology (2 semesters with laboratories, 85.7%), Chemistry (2 semesters with laboratory, 88.9%), Physics (2 semesters with laboratory, 75%), Calculus I (61.1%), and Statistics (Biostatistics 42.9%; General Statistics 13.3%). There was less agreement among programs in regards to Calculus II (20.0%), Organic Chemistry (2 semesters, 55.6%), and Biochemistry I (47%), which may be reflective of individual department focus. There was considerable heterogeneity among physiology program course requirements for disciplinary core courses and upper division electives. This report is meant to generate discussion on physiology program curricula in efforts to improve physiology education for majors and assist P-MIG in determining minimal points of consensus as they write the first set of national curricular guidelines for degree programs.
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http://dx.doi.org/10.1152/advan.00179.2019DOI Listing
December 2020

LACE index predicts age-specific unplanned readmissions and mortality after hospital discharge.

Aging Clin Exp Res 2021 Apr 5;33(4):1041-1048. Epub 2020 Jun 5.

Department of Endocrinology, Ashford and St Peter's Hospitals NHS Foundation Trust, Guildford Road, Chertsey, KT16 0PZ, Surrey, UK.

Background: The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality.

Methods: Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0-106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated.

Results: Within LACE index scores of 0-4, 5-9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ = 3364, p < 0.001). Compared with a LACE index score of 0-4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1-9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0-49.9 years): adjusted odds ratio = 16.1 (5.7-45.8, p < 0.001). For those aged 50-59.9, 60-69.9, 70-79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge.

Conclusions: The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.
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http://dx.doi.org/10.1007/s40520-020-01609-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084827PMC
April 2021

Incidence of postpartum haemorrhage defined by quantitative blood loss measurement: a national cohort.

BMC Pregnancy Childbirth 2020 May 6;20(1):271. Epub 2020 May 6.

Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

Background: Visual estimation of blood loss following delivery often under-reports actual bleed volume. To improve accuracy, quantitative blood loss measurement was introduced for all births in the 12 hospitals providing maternity care in Wales. This intervention was incorporated into a quality improvement programme (Obstetric Bleeding Strategy for Wales, OBS Cymru). We report the incidence of postpartum haemorrhage in Wales over a 1-year period using quantitative measurement.

Methods: This prospective, consecutive cohort included all 31,341 women giving birth in Wales in 2017. Standardised training was cascaded to maternity staff in all 12 hospitals in Wales. The training comprised mock-scenarios, a video and team drills. Uptake of quantitative blood loss measurement was audited at each centre. Data on postpartum haemorrhage of > 1000 mL were collected and analysed according to mode of delivery. Data on blood loss for all maternities was from the NHS Wales Informatics Service.

Results: Biannual audit data demonstrated an increase in quantitative measurement from 52.1 to 87.8% (P < 0.001). The incidence (95% confidence intervals, CI) of postpartum haemorrhage of > 1000 mL, > 1500 mL and > 2000 mL was 8.6% (8.3 to 8.9), 3.3% (3.1 to 3.5) and 1.3% (1.2 to 1.4), respectively compared to 5%, 2% and 0.8% in the year before OBS Cymru. The incidence (95% CI) of bleeds of > 1000 mL was similar across the 12 hospitals despite widely varied size, staffing levels and case mix, median (25th to 75th centile) 8.6% (7.8-9.6). The incidence of PPH varied with mode of delivery and was mean (95% CI) 4.9% (4.6-5.2) for unassisted vaginal deliveries, 18.4 (17.1-19.8) for instrumental vaginal deliveries, 8.5 (7.7-9.4) for elective caesarean section and 19.8 (18.6-21.0) for non-elective caesarean sections.

Conclusions: Quantitative measurement of blood loss is feasible in all hospitals providing maternity care and is associated with detection of higher rates of postpartum haemorrhage. These results have implications for the definition of abnormal blood loss after childbirth and for management and research of postpartum haemorrhage.
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http://dx.doi.org/10.1186/s12884-020-02971-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201938PMC
May 2020

Novel CTNND2-TERT fusion in a spindle cell liposarcoma.

Genes Chromosomes Cancer 2020 09 6;59(9):544-548. Epub 2020 May 6.

Department of Pathology, New York University Langone Health, New York, New York, USA.

Soft tissue tumors can be categorized molecularly into two categories: tumors which are known to have recurrent molecular alterations and tumors which do not have consistent recurrent molecular alterations or translocations. These "nontranslocation" associated sarcomas are clinically more aggressive than their more stable counterparts. However, recent advances in RNA sequencing have discovered recurrent novel fusions within the latter group, namely TERT-TRIO fusions. Furthermore, a recent report discovered this fusion in a spindle cell liposarcoma. Our case describes a novel fusion of CTNND2, a neighbor gene of TRIO, and TERT in a spindle cell liposarcoma, and provides further evidence that spindle cell liposarcoma should be a distinct entity from dedifferentiated liposarcoma.
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http://dx.doi.org/10.1002/gcc.22856DOI Listing
September 2020

A student initiative to implement peer-led study groups for a pharmacogenomics course: Evaluation of student performance and perceptions.

Curr Pharm Teach Learn 2020 05 21;12(5):549-557. Epub 2020 Feb 21.

Department of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, 412 E. Spokane Falls Blvd., Spokane, WA 99202, United States. Electronic address:

Introduction: To better elucidate the impact of cooperative learning outside the classroom, a student-initiated research project was conducted to explore the effects of participating in peer-led study groups (PLSGs) on student examination scores and perceptions.

Methods: First-year pharmacy students were given the opportunity to participate in weekly PLSGs for a pharmacogenomics course during spring 2016 and spring 2017. Student exam performance was stratified by those who attended vs. those who did not. Optional pre- and post-course surveys examined student perceptions of PLSGs.

Results: No significant differences were seen between the attendance groups in spring 2016. In spring 2017, student attendees were significantly more likely to pass two of their six exams (p = .04, p = .0029) and to have higher exam scores on one exam (p = .02) in comparison to non-attendees. Overall exam score averages were significantly different between attendees and non-attendees during spring 2017 (p = .03) but not during spring 2016 (p = .38). Perception surveys indicated students believed participation helped them to demonstrate competency and build confidence. Additionally, students reported they felt more comfortable clarifying questions during the study groups vs. during class time.

Conclusions: The impact of study group participation on student exam performance was minimal over the two years of data collection, but there were instances where exam scores were positively impacted. Students perceived value in study group participation even if it did not translate directly to improved exam performance on all exams.
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http://dx.doi.org/10.1016/j.cptl.2020.01.013DOI Listing
May 2020

Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma.

Clin Cancer Res 2020 08 16;26(15):3969-3978. Epub 2020 Apr 16.

The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits.

Patients And Methods: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m; arm 1) to high-dose carfilzomib (56 mg/m; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment.

Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms ( = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821-1.370; = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841-.571; = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs.

Conclusions: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m dosing of carfilzomib over the 27 mg/m dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415520PMC
August 2020

Designing and implementing an all Wales postpartum haemorrhage quality improvement project: OBS Cymru (the Obstetric Bleeding Strategy for Wales).

BMJ Open Qual 2020 04;9(2)

Haematology, University Hospital of Wales, Cardiff, UK.

Background: Postpartum haemorrhage (PPH) contributes to substantial maternal morbidity. Research into PPH has led to improvements in care which have been incorporated into the Obstetric Bleeding Strategy for Wales.

Intervention: A national quality improvement team supported local teams in implementing multiple interventions including risk assessment, objective measurement of blood loss, multiprofessional assessment (at the bedside at 1000 mL blood loss) and point-of-care (POC) testing of coagulation to guide blood product resuscitation during PPH. The project was rolled out to all 12 obstetric units in 2017. The interventions were reinforced by an All Wales Guideline, PPH proforma and standardised training. A national database, biannual audits, and patient and staff surveys reported process and outcome measures.

Results: Process measures: during 2017, there was an increase in the percentage of maternities with documented risk assessment (0%-76%), objective measurement of blood loss (52%-88%) and POC testing for coagulation for PPH ≥1500 mL (38%-59%). Maternity staff survey indicated that 94% were aware of the project and 87% stated that it had changed their unit's management of PPH. Interim outcome measures: the incidence (95% CI) of PPH ≥2500 mL per 1000 maternities in 2017 was 6.03 (5.23-6.95). The annual number of women receiving any red blood cell transfusion, level 3 intensive care admission and hysterectomy for PPH was 19.7 (18.2 to 21.3), 0.702 (0.464 to 1.06) and 0.255 (0.129 to 0.504) per 1000 maternities, respectively.

Conclusions: A high level of project awareness across Welsh maternity units has been achieved. Measurement of blood loss was reported to be the most important early change in practice, while PPH documentation and POC testing continue to be embedded. Combining qualitative and quantitative measures to inform implementation has improved project delivery and allowed teams to adapt to local contexts.
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http://dx.doi.org/10.1136/bmjoq-2019-000854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326295PMC
April 2020

CD8 T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens.

Mol Ther 2020 05 3;28(5):1238-1250. Epub 2020 Mar 3.

Inovio Pharmaceuticals, Plymouth Meeting, PA, USA.

The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated therapy remains an unmet clinical need. INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). This phase 1/2, open-label, multi-center study enrolled men with PCa with rising PSA after surgery and/or radiation therapy. Patients were enrolled into one of four treatment arms: arm A, 2 mg of INO-5150; arm B, 8.5 mg of INO-5150; arm C, 2 mg of INO-5150 + 1 mg of INO-9012; and arm D, 8.5 mg of INO-5150 + 1 mg of INO-9012. Patients received study drug with electroporation on day 0 and on weeks 3, 12, and 24, and they were followed for up to 72 weeks. Sixty-two patients were enrolled. Treatment was well tolerated. 81% (50/62) of patients completed all visits. 85% (53/62) remained progression-free at 72 weeks. PSA doubling time (PSADT) was increased when assessed in patients with day 0 PSADT ≤12 months. Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).
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http://dx.doi.org/10.1016/j.ymthe.2020.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210698PMC
May 2020
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