Recent Submissions

  • Antimicrobial Photodynamic Therapy as a Potential Treatment Against COVID-19: A Case for Blue Light

    Enwemeka, Chukuka S; Baker, Terrance L; Greiner, Jack V; Bumah, Violet V; Masson-Meyers, Daniela S; Castel, John Chris; Vesonder, Modesta (Mary Ann Liebert Inc., 2020-09-08)
  • Retention-in-care in the PMTCT cascade: definitions matter! Analyses from the INSPIRE projects in Malawi, Nigeria and Zimbabwe

    Font, Helene; Rollins, Nigel; Essajee, Shaffiq; Becquet, Renaud; Foster, Geoff; Mangwiro, Alexio-Zambezio; Mwapasa, Victor; Oyeledun, Bolanle; Phiri, Sam; Sam-Agudu, Nadia A; et al.
    INTRODUCTION: Definitions of retention-in-care in Prevention of Mother-to-Child Transmission of HIV (PMTCT) vary substantially between studies and programmes. Some definitions are based on visits missed/made, others on a minimum total number of visits, or attendance at a final clinic visit at a specific time. An agreed definition could contribute to developing evidence-based interventions for improving retention-in-care. In this paper, we estimated retention-in-care rates according to different definitions, and we quantified and visualized the degree of agreement between definitions. METHODS: We calculated retention in care rates using nine definitions in the six INSPIRE PMTCT intervention studies, conducted in three sub-Saharan African countries between 2013 and 2017. With data from one of the studies (E4E), we estimated the agreement between definitions using Gwet's agreement coefficient (AC1) and concordance. We calculated positive predictive values (PPV) and negative predictive values (NPV) for all definitions considering successively each definition as the reference standard. Finally, we used a Multiple Correspondence Analysis (MCA) to examine clustering of the way different definitions handle retention-in-care. RESULTS: Retention-in-care rates among 5107 women ranged from 30% to 76% in the complete dataset with Gwet's AC1 being 0.56 [0.53; 0.59] indicating a moderate agreement between all definitions together. Two pairs of definitions with high inner concordance and agreement had either very high PPV or very high NPV, and appeared distinct from the other five definitions on the MCA figures. These pairs of definitions were also the ones resulting in the lowest and highest estimates of retention-in-care. The simplest definition, that only required a final clinic visit to classify women as retained in care, and classified 55% of women as retained in care, had a PPV ranging from 0.7 to 1 and a NPV ranging from 0.69 to 0.98 when excluding the two pairs afore-mentioned; it resulted in a moderate to substantial agreement and a 70% to 90% concordance with all other definitions. CONCLUSIONS: Our study highlights the variability of definitions in estimating retention-in-care. Some definitions are very stringent which may be required in some instances. A simple indicator such as attendance at a single time point may be sufficient for programme planning and evaluation.
  • Brain tumor-derived extracellular vesicles as carriers of disease markers: Molecular chaperones and micrornas

    Vitale, Alessandra Maria; Santonocito, Radha; Vergilio, Giuseppe; Gammazza, Antonella Marino; Campanella, Claudia; de Macario, Everly Conway; Bucchieri, Fabio; Macario, Alberto J.L.; Bavisotto, Celeste Caruso (MDPI AG, 2020-10-01)
    Primary and metastatic brain tumors are usually serious conditions with poor prognosis, which reveal the urgent need of developing rapid diagnostic tools and efficacious treatments. To achieve these objectives, progress must be made in the understanding of brain tumor biology, for example, how they resist natural defenses and therapeutic intervention. One resistance mechanism involves extracellular vesicles that are released by tumors to meet target cells nearby or distant via circulation and reprogram them by introducing their cargo. This consists of different molecules among which are microRNAs (miRNAs) and molecular chaperones, the focus of this article. miRNAs modify target cells in the immune system to avoid antitumor reaction and chaperones are key survival molecules for the tumor cell. Extracellular vesicles cargo reflects the composition and metabolism of the original tumor cell; therefore, it is a source of markers, including the miRNAs and chaperones discussed in this article, with potential diagnostic and prognostic value. This and their relatively easy availability by minimally invasive procedures (e.g., drawing venous blood) illustrate the potential of extracellular vesicles as useful materials to manage brain tumor patients. Furthermore, understanding extracellular vesicles circulation and interaction with target cells will provide the basis for using this vesicle for delivering therapeutic compounds to selected tumor cells. © 2020 by the authors.
  • Dalbavancin in the Treatment of Bacteremia and Endocarditis in People with Barriers to Standard Care

    Ajaka, Leama; Heil, Emily; Schmalzle, Sarah (MDPI AG, 2020-10-15)
    Introduction: Dalbavancin is an antibiotic administered by intravenous infusion weekly or bi-weekly and is currently FDA-approved only for treatment of skin and soft-tissue infections. It has shown promise, but is not considered the standard of care, for bacteremia and infective endocarditis (IE), which typically require outpatient parenteral antibiotic therapy (OPAT) for prolonged durations. People who inject drugs (PWID) with bacteremia or IE are often perceived as having barriers to OPAT and standard daily-administered antibiotics, prompting off-label use of dalbavancin in this population. Methods: A retrospective review of adult patients receiving at least one dose of dalbavancin for bacteremia or IE was conducted between 1 November 2017 and 31 October 2019. Outcomes and reasons for use of dalbavancin were recorded, including specific barriers to standard therapy. Results: Stated reasons for dalbavancin use in the 18 patients identified included active injection drug use (50%), inability to arrange standard OPAT due to patient adherence or inability to place in skilled nursing facility (SNF) (22%), risk for additional infections or other morbidity with OPAT (22%), and patient preference (6%). In 11 patients (61%) SNF placement was not attempted due to behavioral issues or patient declination. There were five patients who did not complete their intended course of treatment (28%). At 90 days, eight patients (44%) achieved a clinical or biologic cure, six (33%) failed treatment, and four (22%) were lost to follow-up. Conclusion: Dalbavancin may have a role as salvage therapy in the treatment of IE and bacteremia in PWID who have significant barriers to standard treatment. © 2020 by the authors.
  • Characterization of cardiac mechanics and incident atrial fibrillation in participants of the Cardiovascular Health Study

    Patel, Ravi B; Delaney, Joseph A; Hu, Mo; Patel, Harnish; Cheng, Jeanette; Gottdiener, John; Kizer, Jorge R; Marcus, Gregory M; Turakhia, Mintu P; Deo, Rajat; et al. (The American Society for Clinical Investigation, 2020-10-02)
    BACKGROUND: Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear. METHODS: In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF. RESULTS: Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (heart rate [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain. CONCLUSION: Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF.
  • Light Energy Dose and Photosensitizer Concentration Are Determinants of Effective Photo-Killing against Caries-Related Biofilms

    Balhaddad, Abdulrahman A; AlQranei, Mohammed S; Ibrahim, Maria S; Weir, Michael D; Martinho, Frederico C; Xu, Hockin H K; Melo, Mary Anne S (MDPI AG, 2020-10-15)
    Caries-related biofilms and associated complications are significant threats in dentistry, especially when biofilms grow over dental restorations. The inhibition of cariogenic biofilm associated with the onset of carious lesions is crucial for preventing disease recurrence after treatment. This in vitro study defined optimized parameters for using a photosensitizer, toluidine blue O (TBO), activated via a red light-emitting diode (LED)-based wireless device to control the growth of cariogenic biofilms. The effect of TBO concentrations (50, 100, 150, and 200 μg/mL) exposed to light or incubated in the dark was investigated in successive cytotoxicity assays. Then, a mature Streptococcus mutans biofilm model under sucrose challenge was treated with different TBO concentrations (50, 100, and 150 μg/mL), different light energy doses (36, 108, and 180 J/cm2), and different incubation times before irradiation (1, 3, and 5 min). The untreated biofilm, irradiation with no TBO, and TBO incubation with no activation represented the controls. After treatments, biofilms were analyzed via S. mutans colony-forming units (CFUs) and live/dead assay. The percentage of cell viability was within the normal range compared to the control when 50 and 100 μg/mL of TBO were used. Increasing the TBO concentration and energy dose was associated with biofilm inhibition (p < 0.001), while increasing incubation time did not contribute to bacterial elimination (p > 0.05). Irradiating the S. mutans biofilm via 100 μg/mL of TBO and ≈180 J/cm2 energy dose resulted in ≈3-log reduction and a higher amount of dead/compromised S. mutans colonies in live/dead assay compared to the control (p < 0.001). The light energy dose and TBO concentration optimized the bacterial elimination of S. mutans biofilms. These results provide a perspective on the determining parameters for highly effective photo-killing of caries-related biofilms and display the limitations imposed by the toxicity of the antibacterial photodynamic therapy's chemical components. Future studies should support investigations on new approaches to improve or overcome the constraints of opportunities offered by photodynamic inactivation of caries-related biofilms.
  • Loss of antiphospholipid antibody positivity post-thrombosis in SLE

    Khawaja, Muznay; Magder, Laurence; Goldman, Daniel; Petri, Michelle A
    Background/Purpose Loss of positivity of antiphospholipid antibodies has been observed in clinical practice post-thrombosis in patients with SLE with secondary antiphospholipid syndrome (APS). Our study defined the frequency of this loss and the duration before positivity recurred. Methods In this prospective study, patients with SLE having at least two positive antiphospholipid markers prior to thrombosis and at least 1 year of follow-up after thrombosis were included. Antiphospholipid markers included lupus anticoagulant (dilute Russell viper venom test >45 s followed by mixing and confirmatory tests) and/or anticardiolipin titre (aCL IgG ≥20, aCL IgM ≥20 and/or aCL IgA ≥20). The percentage of visits with positive antiphospholipid markers after thrombosis was calculated. For patients with a negative antiphospholipid marker any time after thrombosis, survival estimates were performed to calculate the time to return of antiphospholipid positivity. Results In APS due to SLE, complete loss of antiphospholipid positivity post-thrombosis was up to 41% for aCL IgG, 51% for IgM and 50% for IgA, but only 20% for those with lupus anticoagulant. Of those who at some point lost aCL IgG or became negative for lupus anticoagulant, the majority (60% and 76%, respectively) reacquired the antibody within 5 years. In contrast, of those who lost aCL IgM or IgA, fewer reacquired it within 5 years (37% and 17%, respectively). Conclusion Intermittent positivity of antiphospholipid antibodies is present in APS due to SLE. These fluctuations make it difficult to decide on length of anticoagulation. Lupus anticoagulant is more likely to persist post-thrombosis.
  • Clinical Reasoning: A patient with a history of weight loss presenting with seizures

    Tang, Garland; Benavides, David R (Wolters Kluwer Health, 2020-07-10)
  • Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD

    Wang, Shaoteng; Tatman, Micaela; Monteiro, Mervyn J (Springer Nature, 2020-10-07)
    Missense mutations in UBQLN2 cause X-linked dominant inheritance of amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). UBQLN2 belongs to a family of four highly homologous proteins expressed in humans that play diverse roles in maintaining proteostasis, but whether one isoform can substitute for another is not known. Here, we tested whether overexpression of UBQLN1 can alleviate disease in the P497S UBQLN2 mouse model of ALS/FTD by crossing transgenic (Tg) mouse lines expressing the two proteins and characterizing the resulting genotypes using a battery of pathologic and behavioral tests. The pathologic findings revealed UBQLN1 overexpression dramatically reduced the burden of UBQLN2 inclusions, neuronal loss and disturbances in proteostasis in double Tg mice compared to single P497S Tg mice. The beneficial effects of UBQLN1 overexpression were primarily confirmed by behavioral improvements seen in rotarod performance and grip strength in male, but not female mice. Paradoxically, although UBQLN1 overexpression reduced pathologic signatures of disease in P497S Tg mice, female mice had larger percentage of body weight loss than males, and this correlated with a corresponding lack of behavioral improvements in the females. These findings lead us to speculate that methods to upregulate UBQLN1 expression may reduce pathogenicity caused by UBQLN2 mutations, but may also lead to gender-specific outcomes that will have to be carefully weighed with the therapeutic benefits of UBQLN1 upregulation.
  • An evaluation of the coverage of theoretically based implementation factors in disseminated classroom physical activity programs

    Calvert, Hannah G; Lane, Hannah G; Bejarano, Carolina M; Snow, Kelli; Hoppe, Kate; Alfonsin, Nicole; Turner, Lindsey; Carlson, Jordan A
    Classroom-based physical activity (CBPA) is increasingly recommended as a method to support children's physical activity, health, and academic performance. Many adoption-ready programs exist to aid in the implementation of CBPA in schools; yet, implementation rates remain low. The purpose of this study was to evaluate the extent to which resources provided by adoption-ready CBPA programs addressed theory-based implementation contextual factors to support implementation. Existing CBPA programs (N = 37) were identified through Internet searches and all materials (e.g., implementation guides) provided by each program were coded for their inclusion of 51 implementation factors based on the Consolidated Framework for Implementation Research (CFIR). Analyses were conducted to compare inclusion of implementation factors across CFIR Domains and by three program groupings: free (yes/no), research evidence (yes/no), and targeted to teacher only (vs. school). Programs covered a mean of 25.9 per cent (SD = 18.7 per cent) of the 14 Inner Setting implementation factors, 34.2 per cent (SD = 18.0 per cent) of the 6 Characteristics of Individuals implementation factors, and 34.8 per cent (SD = 24.3 per cent) of the 8 Process implementation factors. Programs with research evidence covered more implementation factors than programs without research evidence (43.7 vs. 25.9 per cent; p < .05). Although numerous adoption-ready CBPA programs are available and have many strengths, their inclusion of theory-based factors that support or inhibit implementation is generally low. Consideration of such factors, including organizational climate and teacher-level behavior change, is likely critical to supporting ongoing school-wide implementation of CBPA. Research is needed to develop and test effective strategies for addressing these factors to support more widespread CBPA implementation. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.
  • Cause of Stent Failure in Patients on Hemodialysis

    Sato, Yu; Finn, Aloke V; Virmani, Renu (Wiley-Blackwell, 2020-09-23)
  • A Systematic Review of the Hematopoietic Acute Radiation Syndrome (H-ARS) in Canines and Non-human Primates: Acute Mixed Neutron/Gamma vs. Reference Quality Radiations

    MacVittie, Thomas J; Farese, Ann M; Jackson, William E
    A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and US HHS RePORT (2002-present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1-2 MeV x radiation and Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1-2 MeV x radiation and Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956-2012.
  • Understanding the gaps in DR-TB care cascade in Nigeria: A sequential mixed-method study

    Oga-Omenka, Charity; Boffa, Jody; Kuye, Joseph; Dakum, Patrick; Menzies, Dick; Zarowsky, Christina (Elsevier Ltd., 2020-12-01)
    Background: Despite the availability of free drug-resistant tuberculosis (DR-TB) care in Nigeria since 2011, the country continues to tackle low case notification and treatment rates. In 2018, 11% of an estimated 21,000 cases were diagnosed and 9% placed on treatment. These low rates are nevertheless a marked improvement from 2015 when only 3.4% were diagnosed and 2.3% placed on treatment of an estimated 29,000 cases. This study describes the Nigerian DR-TB care cascade from 2013 to 2017 and considers factors influencing gaps in care. Methods: Our study utilized a mixed-method design. For the quantitative component, we utilized the national diagnosis and treatment databases, as well as the World Health Organization's estimates for prevalence to construct a 5-year care cascade: numbers of patients at each level of DR-TB care, including incident cases, individuals who accessed testing, were diagnosed, initiated treated and completed treatment in Nigeria between 2013 and 2017. Using retrospective data for patients diagnosed in 2015, we performed the Fisher's exact test to determine the association between patient (age and gender) and provider/patient (region- north or south) variables, permitting a closer look at the gaps in care revealed across the 5 years. Barriers to care were explored using framework thematic analysis of 57 qualitative interviews and focus group discussions with patients, including 5 cases not initiated on treatment from the 2015 cohort, treatment supporters, community members, healthcare workers and program managers in 2017. Results: A 5-year analysis of cascade of care data shows significant, but inadequate, increases in overall numbers of cases accessing care. On average, between 2013 and 2017, 80% of estimated cases did not access testing; 75% of those who tested were not diagnosed; 36% of those diagnosed were not initiated on treatment and 23% of these did not finish treatment. In 2015, children and patients in Northern Nigeria had odds of 0.3 [95% CI 0.1–0.7] and 0.4 [0.3–0.5] of completing treatment once diagnosed; while males were shown to have a 1.34 [95% CI 1.0–1.7] times greater chance of completing treatment after diagnosis. The main themes from qualitative data identified barriers to care along the care cascade at individual, family and community, as well as health systems levels. At the individual level, a lack of awareness of the true cause of disease and the availability of ‘free’ care was a recurring theme. Family interference was found to be a particular challenge for children and women. At the health system level, low index of suspicion, lack of rapid diagnostic tools and human resource shortages appeared to limit patients’ access. Conclusions: Any gains in diagnostic technology and shorter regimens are lost with inadequate access to DR-TB services. The biggest losses in the Nigerian cascade happen before treatment initiation. There is a need for urgent action on identified gaps in the DR-TB cascade in order to improve care continuity at multiple stages, improve health service delivery and facilitate TB control in Nigeria.
  • The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

    Murugan, Madhuvika; Zheng, Jiaying; Wu, Gongxiong; Mogilevsky, Rochelle; Zheng, Xin; Hu, Peiwen; Wu, Junfang; Wu, Long-Jun (Springer Nature, 2020-10-20)
    Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1-/-) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1-/- mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1-/- mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.
  • Prevalence and trends of chronic kidney disease and its risk factors among US adults: An analysis of NHANES 2003-18

    Kibria, Gulam Muhammed Al; Crispen, Reese (Elsevier Ltd., 2020-12-01)
    Chronic kidney disease (CKD) is a leading cause of mortalities, morbidities, and health-care costs in the United States; however, limited number of recent studies estimated the burden of CKD and its risk factors together. This cross-sectional study estimated the age-adjusted prevalence and trends of CKD and its risk factors, and the prevalence and trends of CKD according to presence of risk factors. We analyzed National Health and Nutrition Examination Survey 2003–18 data. Individuals aged ≥20 years with albumin-creatinine ratio ≥30 mg/g or glomerular filtration rate <60 ml/min/1.73 m2 were considered to have CKD. Following variables were considered as risk factors: hypertension, diabetes, high total cholesterol, high triglyceride, low high-density lipoprotein (HDL), obesity, abdominal obesity, insufficient aerobic physical activity (PA), and current tobacco smoking. Trends were compared by chi-square tests. The age-adjusted prevalence (95% confidence interval) for CKD was 14.1% (13.1%–15.0%), 13.0% (12.3%–13.8%), 14.0% (13.0%–15.1%), and 13.3% (12.3%–14.4%) in 2003–06, 2007–10, 2011–14, and 2015–18, respectively (p[trend] = 0.24, N = 39569). This prevalence change was also minimal for most CKD stages. Non-Hispanic blacks and low-income people had a higher prevalence than all other races/ethnicities and income groups in most periods. Among risk factors, the prevalence of diabetes, high triglyceride, high total cholesterol, low HDL, obesity, abdominal obesity, and metabolic syndrome increased (p[trend] <0.05). The prevalence of hypertension remained static. The prevalence of current tobacco smoking and insufficient aerobic PA declined. The age-adjusted prevalence of CKD has plateaued; however, the prevalence of some risk factors is increasing. Reducing the burden of these risk factors is also essential to reduce the prevalence of CKD. © 2020 The Authors
  • The use of venous Doppler to predict adverse kidney events in a general ICU cohort

    Spiegel, Rory; Teeter, William; Sullivan, Scott; Tupchong, Keegan; Mohammed, Nabeel; Sutherland, Mark; Leibner, Evan; Rola, Philippe; Galvagno, Samuel M; Murthi, Sarah B (Springer Nature, 2020-10-19)
    Background: Changes in Doppler flow patterns of hepatic veins (HV), portal vein (PV) and intra-renal veins (RV) reflect right atrial pressure and venous congestion; the feasibility of obtaining these assessments and the clinical relevance of the findings is unknown in a general ICU population. This study compares the morphology of HV, PV and RV waveform abnormalities in prediction of major adverse kidney events at 30 days (MAKE30) in critically ill patients. Study design and methods: We conducted a prospective observational study enrolling adult patients within 24 h of admission to the ICU. Patients underwent an ultrasound evaluation of the HV, PV and RV. We compared the rate of MAKE-30 events in patients with and without venous flow abnormalities in the hepatic, portal and intra-renal veins. The HV was considered abnormal if S to D wave reversal was present. The PV was considered abnormal if the portal pulsatility index (PPI) was greater than 30%. We also examined PPI as a continuous variable to assess whether small changes in portal vein flow was a clinically important marker of venous congestion. Results: From January 2019 to June 2019, we enrolled 114 patients. HV abnormalities demonstrate an odds ratio of 4.0 (95% CI 1.4–11.2). PV as a dichotomous outcome is associated with an increased odds ratio of MAKE-30 but fails to reach statistical significance (OR 2.3 95% CI 0.87–5.96), but when examined as a continuous variable it demonstrates an odds ratio of 1.03 (95% CI 1.00–1.06). RV Doppler flow abnormalities are not associated with an increase in the rate of MAKE-30 Interpretation: Obtaining hepatic, portal and renal venous Doppler assessments in critically ill ICU patients are feasible. Abnormalities in hepatic and portal venous Doppler are associated with an increase in MAKE-30. Further research is needed to determine if venous Doppler assessments can be useful measures in assessing right-sided venous congestion in critically ill patients. © 2020, The Author(s).
  • School Closures During COVID-19: Opportunities for Innovation in Meal Service

    Kinsey, Eliza W; Hecht, Amelie A; Dunn, Caroline Glagola; Levi, Ronli; Read, Margaret A; Smith, Courtney; Niesen, Pamela; Seligman, Hilary K; Hager, Erin R (American Public Health Association, 2020-09-17)
    In 2019, the National School Lunch Program and School Breakfast Program served approximately 15 million breakfasts and 30 million lunches daily at low or no cost to students.Access to these meals has been disrupted as a result of long-term school closures related to the COVID-19 pandemic, potentially decreasing both student nutrient intake and household food security. By the week of March 23, 2020, all states had mandated statewide school closures as a result of the pandemic, and the number of weekly missed breakfasts and lunches served at school reached a peak of approximately 169.6 million; this weekly estimate remained steady through the final week of April.We highlight strategies that states and school districts are using to replace these missed meals, including a case study from Maryland and the US Department of Agriculture waivers that, in many cases, have introduced flexibility to allow for innovation. Also, we explore lessons learned from the pandemic with the goal of informing and strengthening future school nutrition policies for out-of-school time, such as over the summer.
  • Testing for Severe Acute Respiratory Syndrome-Coronavirus 2: Challenges in Getting Good Specimens, Choosing the Right Test, and Interpreting the Results

    Tu, Yuan-Po; O'Leary, Timothy J (Wolters Kluwer Health, 2020-11-01)
    OBJECTIVES: We explore ways to reduce errors in laboratory diagnosis of severe acute respiratory syndrome-coronavirus 2 infection by considering preanalytic, analytic, and postanalytic sources. To address preanalytic challenges, we first consider alternative anatomic sites for specimen collection, then discuss self-collection, alternative sampling devices, and transport media. Strengths and limitations of various analytic test systems are considered in the context of postanalytic challenges associated with making test results meaningful, specifically considering the complex relationship between "positive" test results and reproduction and shedding of intact virus. Finally, we provide recommendations regarding healthcare worker surveillance and release of patients with coronavirus disease 2019 from isolation. DATA SOURCES: Material was derived from a Webinar available to the public, manufacturer's websites, U.S. Food and Drug Administration, and Centers for Disease Control and Prevention websites and from both peer-reviewed papers identified by PubMed search and nonpeer-reviewed papers posted on Biorxiv and Medrxiv. Unpublished data came from the Washington State Department of Health. STUDY SELECTION: We included studies that compared diagnostic performance strategies without introducing bias due to use of an imperfect gold standard. Case series and case reports were included as necessary to illuminate the significance of results. DATA EXTRACTION: Data were extracted manually. DATA SYNTHESIS: Sensitivity, specificity, and CIs were computed from article data using a composite reference standard. Nucleic acid-based tests were assumed to perform at 100% specificity. CONCLUSIONS: Although sputum and bronchoalveolar lavage samples provide the highest diagnostic sensitivity for severe acute respiratory syndrome-coronavirus 2, nasopharyngeal, mid turbinate, and nasal specimens are suitable in most cases and require less use of personal protective equipment. When desired sampling materials are unavailable, alternatives may be substituted with no loss of performance. Both reverse transcriptase polymerase chain reaction tests and rapid nucleic acid-based tests offer good performance in most circumstances. Testing is not required to release most patients from isolation.
  • Ethical conflicts in COVID-19 times

    Vizcaino, Gilberto; Esparza, José Gilberto (Open Learning on Enteric Pathogens, 2020-09-30)
    The COVID-19 pandemic has created new challenges on multiple fronts including a few ethical concerns. Timely and appropriate access to health services and the need to protect vulnerable people are some of them. An important aspect to consider, at the global level, is the frailty of health systems in many developing countries and the constant threat of these collapsing due to shortage of resources and medical supply. Special attention should be placed towards protecting the health of care workers who are highly exposed to SARS-CoV-2 infection. Research and clinical trials involving COVID-19 patients and healthy human volunteers must be done in strict adherence to the fundamental principles of bioethics, even if finding a solution is an urgent need. Shared responsibility must be assumed as we collectively face a common problem and ethical conflicts must be resolved using, as reference, the guidelines developed by the World Health Organization and other relevant international and national organizations. This would allow responsible action in the face of the pandemic without harming human rights, the individual and collective well-being.

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