Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Srivastava P[original query] |
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Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States
Adang LA , Bonkowsky JL , Boelens JJ , Mallack E , Ahrens-Nicklas R , Bernat JA , Bley A , Burton B , Darling A , Eichler F , Eklund E , Emrick L , Escolar M , Fatemi A , Fraser JL , Gaviglio A , Keller S , Patterson MC , Orchard P , Orthmann-Murphy J , Santoro JD , Schöls L , Sevin C , Srivastava IN , Rajan D , Rubin JP , Van Haren K , Wasserstein M , Zerem A , Fumagalli F , Laugwitz L , Vanderver A . Cytotherapy 2024 Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care. |
Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty
Howerton E , Contamin L , Mullany LC , Qin M , Reich NG , Bents S , Borchering RK , Jung SM , Loo SL , Smith CP , Levander J , Kerr J , Espino J , van Panhuis WG , Hochheiser H , Galanti M , Yamana T , Pei S , Shaman J , Rainwater-Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Kaminsky J , Hulse JD , Lee EC , McKee CD , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Rosenstrom ET , Ivy JS , Mayorga ME , Swann JL , España G , Cavany S , Moore S , Perkins A , Hladish T , Pillai A , Ben Toh K , Longini I Jr , Chen S , Paul R , Janies D , Thill JC , Bouchnita A , Bi K , Lachmann M , Fox SJ , Meyers LA , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Cadwell BL , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Truelove S , Runge MC , Shea K , Viboud C , Lessler J . Nat Commun 2023 14 (1) 7260 Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections. |
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US (preprint)
Cramer EY , Ray EL , Lopez VK , Bracher J , Brennen A , Castro Rivadeneira AJ , Gerding A , Gneiting T , House KH , Huang Y , Jayawardena D , Kanji AH , Khandelwal A , Le K , Mühlemann A , Niemi J , Shah A , Stark A , Wang Y , Wattanachit N , Zorn MW , Gu Y , Jain S , Bannur N , Deva A , Kulkarni M , Merugu S , Raval A , Shingi S , Tiwari A , White J , Abernethy NF , Woody S , Dahan M , Fox S , Gaither K , Lachmann M , Meyers LA , Scott JG , Tec M , Srivastava A , George GE , Cegan JC , Dettwiller ID , England WP , Farthing MW , Hunter RH , Lafferty B , Linkov I , Mayo ML , Parno MD , Rowland MA , Trump BD , Zhang-James Y , Chen S , Faraone SV , Hess J , Morley CP , Salekin A , Wang D , Corsetti SM , Baer TM , Eisenberg MC , Falb K , Huang Y , Martin ET , McCauley E , Myers RL , Schwarz T , Sheldon D , Gibson GC , Yu R , Gao L , Ma Y , Wu D , Yan X , Jin X , Wang YX , Chen Y , Guo L , Zhao Y , Gu Q , Chen J , Wang L , Xu P , Zhang W , Zou D , Biegel H , Lega J , McConnell S , Nagraj VP , Guertin SL , Hulme-Lowe C , Turner SD , Shi Y , Ban X , Walraven R , Hong QJ , Kong S , van de Walle A , Turtle JA , Ben-Nun M , Riley S , Riley P , Koyluoglu U , DesRoches D , Forli P , Hamory B , Kyriakides C , Leis H , Milliken J , Moloney M , Morgan J , Nirgudkar N , Ozcan G , Piwonka N , Ravi M , Schrader C , Shakhnovich E , Siegel D , Spatz R , Stiefeling C , Wilkinson B , Wong A , Cavany S , España G , Moore S , Oidtman R , Perkins A , Kraus D , Kraus A , Gao Z , Bian J , Cao W , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Vespignani A , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Xiong X , Zheng A , Baek J , Farias V , Georgescu A , Levi R , Sinha D , Wilde J , Perakis G , Bennouna MA , Nze-Ndong D , Singhvi D , Spantidakis I , Thayaparan L , Tsiourvas A , Sarker A , Jadbabaie A , Shah D , Della Penna N , Celi LA , Sundar S , Wolfinger R , Osthus D , Castro L , Fairchild G , Michaud I , Karlen D , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Lee EC , Dent J , Grantz KH , Hill AL , Kaminsky J , Kaminsky K , Keegan LT , Lauer SA , Lemaitre JC , Lessler J , Meredith HR , Perez-Saez J , Shah S , Smith CP , Truelove SA , Wills J , Marshall M , Gardner L , Nixon K , Burant JC , Wang L , Gao L , Gu Z , Kim M , Li X , Wang G , Wang Y , Yu S , Reiner RC , Barber R , Gakidou E , Hay SI , Lim S , Murray C , Pigott D , Gurung HL , Baccam P , Stage SA , Suchoski BT , Prakash BA , Adhikari B , Cui J , Rodríguez A , Tabassum A , Xie J , Keskinocak P , Asplund J , Baxter A , Oruc BE , Serban N , Arik SO , Dusenberry M , Epshteyn A , Kanal E , Le LT , Li CL , Pfister T , Sava D , Sinha R , Tsai T , Yoder N , Yoon J , Zhang L , Abbott S , Bosse NI , Funk S , Hellewell J , Meakin SR , Sherratt K , Zhou M , Kalantari R , Yamana TK , Pei S , Shaman J , Li ML , Bertsimas D , Skali Lami O , Soni S , Tazi Bouardi H , Ayer T , Adee M , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller P , Xiao J , Wang Y , Wang Q , Xie S , Zeng D , Green A , Bien J , Brooks L , Hu AJ , Jahja M , McDonald D , Narasimhan B , Politsch C , Rajanala S , Rumack A , Simon N , Tibshirani RJ , Tibshirani R , Ventura V , Wasserman L , O'Dea EB , Drake JM , Pagano R , Tran QT , Ho LST , Huynh H , Walker JW , Slayton RB , Johansson MA , Biggerstaff M , Reich NG . medRxiv 2021 2021.02.03.21250974 Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information& Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44 |
Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination (preprint)
Truelove S , Smith CP , Qin M , Mullany LC , Borchering RK , Lessler J , Shea K , Howerton E , Contamin L , Levander J , Salerno J , Hochheiser H , Kinsey M , Tallaksen K , Wilson S , Shin L , Rainwater-Lovett K , Lemaitre JC , Dent J , Kaminsky J , Lee EC , Perez-Saez J , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Piontti APY , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Schlitt J , Corbett P , Telionis PA , Wang L , Peddireddy AS , Hurt B , Chen J , Vullikanti A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana T , Pei S , Shaman J , Reich NG , Healy JM , Slayton RB , Biggerstaff M , Johansson MA , Runge MC , Viboud C . medRxiv 2021 WHAT IS ALREADY KNOWN ABOUT THIS TOPIC? The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July-December 2021. WHAT IS ADDED BY THIS REPORT? Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July-December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE? Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen. |
Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study (preprint)
Borchering RK , Mullany LC , Howerton E , Chinazzi M , Smith CP , Qin M , Reich NG , Contamin L , Levander J , Kerr J , Espino J , Hochheiser H , Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Hulse JD , Kaminsky J , Lee EC , Davis JT , Mu K , Xiong X , Pastore y Piontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana T , Pei S , Shaman J , Espana G , Cavany S , Moore S , Perkins A , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Shea K , Truelove SA , Runge MC , Viboud C , Lessler J . medRxiv 2022 10 Background SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. |
Implementation of an antibiotic stewardship initiative in a large urgent care network
Stenehjem E , Wallin A , Willis P , Kumar N , Seibert AM , Buckel WR , Stanfield V , Brunisholz KD , Fino N , Samore MH , Srivastava R , Hicks LA , Hersh AL . JAMA Netw Open 2023 6 (5) e2313011 IMPORTANCE: Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. OBJECTIVE: To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493 724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. INTERVENTIONS: Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. RESULTS: The baseline period included 207 047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183 893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. CONCLUSIONS AND RELEVANCE: The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship. |
Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.
Anesi GL , Andrews A , Bai HJ , Bhatraju PK , Brett-Major DM , Broadhurst MJ , Campbell ES , Cobb JP , Gonzalez M , Homami S , Hypes CD , Irwin A , Kratochvil CJ , Krolikowski K , Kumar VK , Landsittel DP , Lee RA , Liebler JM , Lutrick K , Marts LT , Mosier JM , Mukherjee V , Postelnicu R , Rodina V , Segal LN , Sevransky JE , Spainhour C , Srivastava A , Uyeki TM , Wurfel MM , Wyles D , Evans L . Crit Care Med 2023 51 (4) 445-459 OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked. |
Considerations to improve pediatric HIV testing and close the treatment gap in 16 African countries
Gross J , Medley A , Rivadeneira E , Battey K , Srivastava M , Grillo M , Wolf H , Simmons P , Hast M , Patel M . Pediatr Infect Dis J 2023 42 (2) 110-118 BACKGROUND: In 2019, South Africa, Nigeria, Tanzania, Democratic Republic of Congo, Uganda, Mozambique, Zambia, Angola, Cameroon, Zimbabwe, Ghana, Ethiopia, Malawi, Kenya, South Sudan and Côte d'Ivoire accounted for 80% of children living with HIV (CLHIV) not receiving HIV treatment. This manuscript describes pediatric HIV testing to inform case-finding strategies. METHODS: We analyzed US President's Emergency Plan for AIDS Relief monitoring, evaluation, and reporting data (October 1, 2018 to September 30, 2019) for these 16 countries. Number of HIV tests and positive results were reported by age band, country, treatment coverage and testing modality. The number needed to test (NNT) to identify 1 new CLHIV 1-14 years was measured by testing modality and country. The pediatric testing gap was estimated by multiplying the estimated number of CLHIV unaware of their status by NNT per country. RESULTS: Among children, 6,961,225 HIV tests were conducted, and 101,762 CLHIV were identified (NNT 68), meeting 17.6% of the pediatric testing need. Index testing accounted for 13.0% of HIV tests (29.7% of positive results, NNT 30), provider-initiated testing and counseling 65.9% of tests (43.6% of positives, NNT 103), and universal testing at sick entry points 5.3% of tests (6.5% of positives, NNT 58). CONCLUSIONS: As countries near HIV epidemic control for adults, the need to increase pediatric testing continues. Each testing modality - PITC, universal testing at sick entry points, and index testing - offers unique benefits. These results illustrate the comparative advantages of including a strategic mix of testing modalities in national programs to increase pediatric HIV case finding. |
Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.
Bhatraju PK , Morrell ED , Stanaway IB , Sathe NA , Srivastava A , Postelnicu R , Green R , Andrews A , Gonzalez M , Kratochvil CJ , Kumar VK , Hsiang TY , Gale M Jr , Anesi GL , Wyles D , Broadhurst MJ , Brett-Major D , Mukherjee V , Sevransky JE , Landsittel D , Hung C , Altemeier WA , Gharib SA , Uyeki TM , Cobb JP , Liebler JM , Crosslin DR , Jarvik GP , Segal LN , Evans L , Mikacenic C , Wurfel MM . Crit Care Explor 2023 5 (1) e0827 Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log(2) increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10(-5)). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients. |
Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: A multi-model study.
Borchering RK , Mullany LC , Howerton E , Chinazzi M , Smith CP , Qin M , Reich NG , Contamin L , Levander J , Kerr J , Espino J , Hochheiser H , Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Hulse JD , Kaminsky J , Lee EC , Hill AL , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana T , Pei S , Shaman J , España G , Cavany S , Moore S , Perkins A , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Shea K , Truelove SA , Runge MC , Viboud C , Lessler J . Lancet Reg Health Am 2023 17 100398 BACKGROUND: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5-11 years on COVID-19 burden and resilience against variant strains. METHODS: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5-11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. FINDINGS: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5-11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. INTERPRETATION: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5-11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. FUNDING: Various (see acknowledgments). |
Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections.
Postelnicu R , Srivastava A , Bhatraju PK , Wurfelc MM , Anesi GL , Gonzalez M , Andrews A , Lutrick K , Kumar VK , Uyeki TM , Cobb PJ , Segal LN , Brett-Major D , Liebler JM , Kratochvil CJ , Mukherjee V , Broadhurst MJ , Lee R , Wyles D , Sevransky JE , Evans L , Landsittel D . Crit Care Explor 2022 4 (10) e0773 Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI. |
Pediatric HIV Case Identification Across 22 PEPFAR-Supported Countries During the COVID-19 Pandemic, October 2019-September 2020.
Traub AM , Medley A , Gross J , Sloan M , Amzel A , Gleason MM , Fernando NB , Wong V , Grillo MP , Wolf HT , Al-Samarrai T , Frawley A , Segwabe M , Motswere C , Baramperanye E , Nzima V , Mange Mayer M , Balachandra S , N'Siesi F X , Longuma HO , Nyembo P , Mazibuko S , Tilahun T , Teferi W , Desinor O , Reginald JL , Simiyu T , Nyabiage L , Mirembe J , Ts'oeu M , Zomba G , Nyangulu M , Wate A , Greenberg Cowan J , Mali D , Pietersen I , Ogundehin D , Onotu D , Ikpeazu A , Niyonsaba E , Bamwesigye J , Mabasa H , Kindra G , Bunga S , Rwegerera F , Machage E , King'ori G , Calnan J , Nazziwa E , Lingenda G , Musokotwane K , Bulaya-Tembo R , Maphosa T , Srivastava M . MMWR Morb Mortal Wkly Rep 2022 71 (28) 894-898 During 2020, an estimated 150,000 persons aged 0-14 years acquired HIV globally (1). Case identification is the first step to ensure children living with HIV are linked to life-saving treatment, achieve viral suppression, and live long, healthy lives. Successful interventions to optimize pediatric HIV testing during the COVID-19 pandemic are needed to sustain progress toward achieving Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.* Changes in HIV testing and diagnoses among persons aged 1-14 years (children) were assessed in 22 U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries during October 1, 2019-September 30, 2020. This period corresponds to the two fiscal quarters before the COVID-19 pandemic (i.e., Q1 and Q2) and the two quarters after the pandemic began (i.e., Q3 and Q4). Testing was disaggregated by age group, testing strategy, and fiscal year quarter. During October 2019-September 2020, PEPFAR supported 4,312,343 HIV tests and identified 74,658 children living with HIV (CLHIV). The number of HIV tests performed was similar during Q1 and Q2, decreased 40.1% from Q2 to Q3, and increased 19.7% from Q3 to Q4. The number of HIV cases identified among children aged 1-14 years (cases identified) increased 7.4% from Q1 to Q2, decreased 29.4% from Q2 to Q3, and increased 3.3% from Q3 to Q4. Although testing in outpatient departments decreased 21% from Q1 to Q4, testing from other strategies increased during the same period, including mobile testing by 38%, facility-based index testing (offering an HIV test to partners and biological children of persons living with HIV) by 8%, and testing children with signs or symptoms of malnutrition within health facilities by 7%. In addition, most tests (61.3%) and cases identified (60.9%) were among children aged 5-14 years (school-aged children), highlighting the need to continue offering HIV testing to older children. These findings provide important information on the most effective strategies for identifying CLHIV during the COVID-19 pandemic. HIV testing programs should continue to use programmatic, surveillance, and financial data at both national and subnational levels to determine the optimal mix of testing strategies to minimize disruptions in pediatric case identification during the COVID-19 pandemic. |
Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.
Truelove S , Smith CP , Qin M , Mullany LC , Borchering RK , Lessler J , Shea K , Howerton E , Contamin L , Levander J , Salerno J , Hochheiser H , Kinsey M , Tallaksen K , Wilson S , Shin L , Rainwater-Lovett K , Lemairtre JC , Dent Hulse J , Kaminsky J , Lee EC , Perez-Saez J , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Orr M , Harrison G , Hurt B , Chen J , Vullikanti A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana TK , Pei S , Shaman JL , Healy JM , Slayton RB , Biggerstaff M , Johansson MA , Runge MC , Viboud C . Elife 2022 11 In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-10 Scenario Modeling Hub, an ensemble of nine mechanistic models produced six-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, though may have had even greater impacts, considering the underestimated resurgence magnitude from the model. |
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.
Cramer EY , Ray EL , Lopez VK , Bracher J , Brennen A , Castro Rivadeneira AJ , Gerding A , Gneiting T , House KH , Huang Y , Jayawardena D , Kanji AH , Khandelwal A , Le K , Mühlemann A , Niemi J , Shah A , Stark A , Wang Y , Wattanachit N , Zorn MW , Gu Y , Jain S , Bannur N , Deva A , Kulkarni M , Merugu S , Raval A , Shingi S , Tiwari A , White J , Abernethy NF , Woody S , Dahan M , Fox S , Gaither K , Lachmann M , Meyers LA , Scott JG , Tec M , Srivastava A , George GE , Cegan JC , Dettwiller ID , England WP , Farthing MW , Hunter RH , Lafferty B , Linkov I , Mayo ML , Parno MD , Rowland MA , Trump BD , Zhang-James Y , Chen S , Faraone SV , Hess J , Morley CP , Salekin A , Wang D , Corsetti SM , Baer TM , Eisenberg MC , Falb K , Huang Y , Martin ET , McCauley E , Myers RL , Schwarz T , Sheldon D , Gibson GC , Yu R , Gao L , Ma Y , Wu D , Yan X , Jin X , Wang YX , Chen Y , Guo L , Zhao Y , Gu Q , Chen J , Wang L , Xu P , Zhang W , Zou D , Biegel H , Lega J , McConnell S , Nagraj VP , Guertin SL , Hulme-Lowe C , Turner SD , Shi Y , Ban X , Walraven R , Hong QJ , Kong S , van de Walle A , Turtle JA , Ben-Nun M , Riley S , Riley P , Koyluoglu U , DesRoches D , Forli P , Hamory B , Kyriakides C , Leis H , Milliken J , Moloney M , Morgan J , Nirgudkar N , Ozcan G , Piwonka N , Ravi M , Schrader C , Shakhnovich E , Siegel D , Spatz R , Stiefeling C , Wilkinson B , Wong A , Cavany S , España G , Moore S , Oidtman R , Perkins A , Kraus D , Kraus A , Gao Z , Bian J , Cao W , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Vespignani A , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Xiong X , Zheng A , Baek J , Farias V , Georgescu A , Levi R , Sinha D , Wilde J , Perakis G , Bennouna MA , Nze-Ndong D , Singhvi D , Spantidakis I , Thayaparan L , Tsiourvas A , Sarker A , Jadbabaie A , Shah D , Della Penna N , Celi LA , Sundar S , Wolfinger R , Osthus D , Castro L , Fairchild G , Michaud I , Karlen D , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Lee EC , Dent J , Grantz KH , Hill AL , Kaminsky J , Kaminsky K , Keegan LT , Lauer SA , Lemaitre JC , Lessler J , Meredith HR , Perez-Saez J , Shah S , Smith CP , Truelove SA , Wills J , Marshall M , Gardner L , Nixon K , Burant JC , Wang L , Gao L , Gu Z , Kim M , Li X , Wang G , Wang Y , Yu S , Reiner RC , Barber R , Gakidou E , Hay SI , Lim S , Murray C , Pigott D , Gurung HL , Baccam P , Stage SA , Suchoski BT , Prakash BA , Adhikari B , Cui J , Rodríguez A , Tabassum A , Xie J , Keskinocak P , Asplund J , Baxter A , Oruc BE , Serban N , Arik SO , Dusenberry M , Epshteyn A , Kanal E , Le LT , Li CL , Pfister T , Sava D , Sinha R , Tsai T , Yoder N , Yoon J , Zhang L , Abbott S , Bosse NI , Funk S , Hellewell J , Meakin SR , Sherratt K , Zhou M , Kalantari R , Yamana TK , Pei S , Shaman J , Li ML , Bertsimas D , Skali Lami O , Soni S , Tazi Bouardi H , Ayer T , Adee M , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller P , Xiao J , Wang Y , Wang Q , Xie S , Zeng D , Green A , Bien J , Brooks L , Hu AJ , Jahja M , McDonald D , Narasimhan B , Politsch C , Rajanala S , Rumack A , Simon N , Tibshirani RJ , Tibshirani R , Ventura V , Wasserman L , O'Dea EB , Drake JM , Pagano R , Tran QT , Ho LST , Huynh H , Walker JW , Slayton RB , Johansson MA , Biggerstaff M , Reich NG . Proc Natl Acad Sci U S A 2022 119 (15) e2113561119 SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action. |
Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021.
Borchering RK , Viboud C , Howerton E , Smith CP , Truelove S , Runge MC , Reich NG , Contamin L , Levander J , Salerno J , van Panhuis W , Kinsey M , Tallaksen K , Obrecht RF , Asher L , Costello C , Kelbaugh M , Wilson S , Shin L , Gallagher ME , Mullany LC , Rainwater-Lovett K , Lemaitre JC , Dent J , Grantz KH , Kaminsky J , Lauer SA , Lee EC , Meredith HR , Perez-Saez J , Keegan LT , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Schlitt J , Corbett P , Telionis PA , Wang L , Peddireddy AS , Hurt B , Chen J , Vullikanti A , Marathe M , Healy JM , Slayton RB , Biggerstaff M , Johansson MA , Shea K , Lessler J . MMWR Morb Mortal Wkly Rep 2021 70 (19) 719-724 After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months. |
Redox epiphospholipidome in programmed cell death signaling: Catalytic mechanisms and regulation
Kagan VE , Tyurina YY , Vlasova II , Kapralov AA , Amoscato AA , Anthonymuthu TS , Tyurin VA , Shrivastava IH , Cinemre FB , Lamade A , Epperly MW , Greenberger JS , Beezhold DH , Mallampalli RK , Srivastava AK , Bayir H , Shvedova AA . Front Endocrinol (Lausanne) 2020 11 628079 A huge diversification of phospholipids, forming the aqueous interfaces of all biomembranes, cannot be accommodated within a simple concept of their role as membrane building blocks. Indeed, a number of signaling functions of (phospho)lipid molecules has been discovered. Among these signaling lipids, a particular group of oxygenated polyunsaturated fatty acids (PUFA), so called lipid mediators, has been thoroughly investigated over several decades. This group includes oxygenated octadecanoids, eicosanoids, and docosanoids and includes several hundreds of individual species. Oxygenation of PUFA can occur when they are esterified into major classes of phospholipids. Initially, these events have been associated with non-specific oxidative injury of biomembranes. An alternative concept is that these post-synthetically oxidatively modified phospholipids and their adducts with proteins are a part of a redox epiphospholipidome that represents a rich and versatile language for intra- and inter-cellular communications. The redox epiphospholipidome may include hundreds of thousands of individual molecular species acting as meaningful biological signals. This review describes the signaling role of oxygenated phospholipids in programs of regulated cell death. Although phospholipid peroxidation has been associated with almost all known cell death programs, we chose to discuss enzymatic pathways activated during apoptosis and ferroptosis and leading to peroxidation of two phospholipid classes, cardiolipins (CLs) and phosphatidylethanolamines (PEs). This is based on the available LC-MS identification and quantitative information on the respective peroxidation products of CLs and PEs. We focused on molecular mechanisms through which two proteins, a mitochondrial hemoprotein cytochrome c (cyt c), and non-heme Fe lipoxygenase (LOX), change their catalytic properties to fulfill new functions of generating oxygenated CL and PE species. Given the high selectivity and specificity of CL and PE peroxidation we argue that enzymatic reactions catalyzed by cyt c/CL complexes and 15-lipoxygenase/phosphatidylethanolamine binding protein 1 (15LOX/PEBP1) complexes dominate, at least during the initiation stage of peroxidation, in apoptosis and ferroptosis. We contrast cell-autonomous nature of CLox signaling in apoptosis correlating with its anti-inflammatory functions vs. non-cell-autonomous ferroptotic signaling facilitating pro-inflammatory (necro-inflammatory) responses. Finally, we propose that small molecule mechanism-based regulators of enzymatic phospholipid peroxidation may lead to highly specific anti-apoptotic and anti-ferroptotic therapeutic modalities. |
Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemic.
Vrazo AC , Golin R , Fernando NB , Killam WP , Sharifi S , Phelps BR , Gleason MM , Wolf HT , Siberry GK , Srivastava M . J Int AIDS Soc 2020 23 (9) e25622 INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts. |
Antibiotic prescribing variability in a large urgent care network: A new target for outpatient stewardship
Stenehjem E , Wallin A , Fleming-Dutra KE , Buckel WR , Stanfield V , Brunisholz KD , Sorensen J , Samore MH , Srivastava R , Hicks LA , Hersh AL . Clin Infect Dis 2019 70 (8) 1781-1787 Improving antibiotic prescribing in outpatient settings is a public health priority. In the United States, urgent care (UC) encounters are increasing and have high rates of inappropriate antibiotic prescribing. Our objective was to characterize antibiotic prescribing practices during UC encounters, with a focus on respiratory tract conditions. This was a retrospective cohort study of UC encounters in the Intermountain Healthcare network. Among 1.16 million UC encounters, antibiotics were prescribed during 34% of UC encounters and respiratory conditions accounted for 61% of all antibiotics prescribed. Of respiratory encounters, 50% resulted in antibiotic prescriptions, yet the variability at the level of the provider ranged from 3% to 94%. Similar variability between providers was observed for respiratory conditions where antibiotics were not indicated and in first-line antibiotic selection for sinusitis, otitis media, and pharyngitis. These findings support the importance of developing antibiotic stewardship interventions specifically targeting UC settings. We describe antibiotic prescribing in a large network of urgent care (UC) clinics. The high volume of infectious diseases encounters and extreme provider variability in antibiotic prescribing frequency and quality highlight the importance of antibiotic stewardship interventions specifically targeting UCs. |
Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding women and their infants: the promise of innovative service delivery models
Srivastava M , Sullivan D , Phelps BR , Modi S , Broyles LN . J Int AIDS Soc 2018 21 (1) INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. DISCUSSION: Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. CONCLUSIONS: Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake of services for families. However, with decreasing funding, stable HIV incidence, and aspirations for sustainability, it is critical to consider efficient, customized and cost-effective models of care for these populations as we aspire to eliminate mother-to-child transmission of HIV. |
Sustained progress, but no room for complacency: Results of 2015 HIV estimations in India
Pandey A , Dhingra N , Kumar P , Sahu D , Reddy DCS , Narayan P , Raj Y , Sangal B , Chandra N , Nair S , Singh J , Chavan L , Srivastava DJ , Jha UM , Verma V , Kant S , Bhattacharya M , Swain P , Haldar P , Singh L , Bakkali T , Stover J , Ammassari S . Indian J Med Res 2017 146 (1) 83-96 BACKGROUND & OBJECTIVES: Evidence-based planning has been the cornerstone of India's response to HIV/AIDS. Here we describe the process, method and tools used for generating the 2015 HIV estimates and provide a summary of the main results. METHODS: Spectrum software supported by the UNAIDS was used to produce HIV estimates for India as a whole and its States/Union Territories. This tool takes into consideration the size and HIV prevalence of defined population groups and programme data to estimate HIV prevalence, incidence and mortality over time as well as treatment needs. RESULTS: India's national adult prevalence of HIV was 0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV infections were an estimated 86,000 in 2015, reflecting a decline by around 32 per cent from 2007. The declining trend in incidence was mirrored in most States, though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh, Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were variations in the rate and trend of decline across India for this indicator also. INTERPRETATION & CONCLUSIONS: While key indicators measured through Spectrum modelling confirm success of the National AIDS Control Programme, there is no room for complacency as rising incidence trends in some geographical areas and population pockets remain the cause of concern. Progress achieved so far in responding to HIV/AIDS needs to be sustained to end the HIV epidemic. |
Biomarkers of exposure to new and emerging tobacco delivery products
Schick SF , Blount BC , Jacob P 3rd , Saliba NA , Bernert JT , El Hellani A , Jatlow P , Pappas RS , Wang L , Foulds J , Ghosh A , Hecht SS , Gomez JC , Martin JR , Mesaros C , Srivastava S , St Helen G , Tarran R , Lorkiewicz PK , Blair IA , Kimmel HL , Doerschuk CM , Benowitz NL , Bhatnagar A . Am J Physiol Lung Cell Mol Physiol 2017 313 (3) ajplung.00343.2016 Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their utility for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipe and cigarillos. Rigorously validated biomarkers specific to these new products are yet to be identified. Here, we discuss the strengths and limitations of current approaches, including whether or not they provide reliable exposure estimates. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately, while avoiding common experimental errors. By identifying the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policy makers and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products. |
Engaging parents to promote children's nutrition and health: Providers' barriers and strategies in Head Start and child care centers
Dev DA , Byrd-Williams C , Ramsay S , McBride B , Srivastava D , Murriel A , Arcan C , Adachi-Mejia AM . Am J Health Promot 2017 31 (2) 153-162 Purpose: Using the Academy of Nutrition and Dietetics benchmarks as a framework, this study examined childcare providers' (Head Start [HS], Child and Adult Care Food Program [CACFP] funded, and non-CACFP) perspectives regarding communicating with parents about nutrition to promote children's health. Design: Qualitative. Setting: State-licensed center-based childcare programs. Participants: Full-time childcare providers (n = 18) caring for children 2 to 5 years old from varying childcare contexts (HS, CACFP funded, and non-CACFP), race, education, and years of experience. Methods: In-person interviews using semi-structured interview protocol until saturation were achieved. Thematic analysis was conducted. Results: Two overarching themes were barriers and strategies to communicate with parents about children's nutrition. Barriers to communication included - (a) parents are too busy to talk with providers, (b) parents offer unhealthy foods, (c) parents prioritize talking about child food issues over nutrition, (d) providers are unsure of how to communicate about nutrition without offending parents, and (e) providers are concerned if parents are receptive to nutrition education materials. Strategies for communication included - (a) recognize the benefits of communicating with parents about nutrition to support child health, (b) build a partnership with parents through education, (c) leverage policy (federal and state) to communicate positively and avoid conflict, (d) implement center-level practices to reinforce policy, and (e) foster a respectful relationship between providers and parents. Conclusion: Policy and environmental changes were recommended for fostering a respectful relationship and building a bridge between providers and parents to improve communication about children's nutrition and health. |
Update: Ebola virus disease epidemic - West Africa, February 2015
CDC Incident Management System Ebola Epidemiology Team , Guinea Interministerial Committee for Response Against the Ebola Virus , World Health Organization , CDC Guinea Response Team , Liberia Ministry of Health and Social Welfare , CDC Liberia Response Team , Sierra Leone Ministry of Health and Sanitation , CDC Sierra Leone Response Team , CDC NCEZID Viral Special Pathogens Branch , Srivastava P . MMWR Morb Mortal Wkly Rep 2015 64 (7) 186-187 CDC is assisting ministries of health and working with other organizations to end the ongoing epidemic of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from situation reports from the Guinea Interministerial Committee for Response Against the Ebola Virus, the Liberia Ministry of Health and Social Welfare, the Sierra Leone Ministry of Health and Sanitation, and the World Health Organization. |
Leveraging biospecimen resources for discovery or validation of markers for early cancer detection.
Schully SD , Carrick DM , Mechanic LE , Srivastava S , Anderson GL , Baron JA , Berg CD , Cullen J , Diamandis EP , Doria-Rose VP , Goddard KA , Hankinson SE , Kushi LH , Larson EB , McShane LM , Schilsky RL , Shak S , Skates SJ , Urban N , Kramer BS , Khoury MJ , Ransohoff DF . J Natl Cancer Inst 2015 107 (4) Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. |
Field evaluation of a real-time fluorescence loop-mediated isothermal amplification assay, RealAmp, for the diagnosis of malaria in Thailand and India
Patel JC , Lucchi NW , Srivastava P , Lin JT , Sug-Aram R , Aruncharus S , Bharti PK , Shukla MM , Congpuong K , Satimai W , Singh N , Udhayakumar V , Meshnick SR . J Infect Dis 2014 210 (8) 1180-7 BACKGROUND: To eliminate malaria, surveillance for submicroscopic infections is needed. Molecular methods can detect submicroscopic infections but have not hitherto been amenable to implementation in surveillance programs. A portable loop-mediated isothermal amplification assay called RealAmp was assessed in 2 areas of low malaria transmission. METHODS: RealAmp was evaluated in 141 patients from health clinics in India (passive surveillance) and in 127 asymptomatic persons in Thailand (active surveillance). The diagnostic validity, precision, and predictive value of RealAmp were determined using polymerase chain reaction (PCR) as the reference method. A pilot study of RealAmp was also performed on samples from patients presenting at a Thai health center. RESULTS: A total of 96 and 7 positive cases were detected in India and Thailand, respectively, via PCR. In comparison with nested PCR, the sensitivity and specificity of RealAmp in India were 94.8% (95% confidence interval [CI], 88.3%-98.3%) and 100% (95% CI, 92.1%-100%), respectively, with correct identification of all 5 Plasmodium vivax cases. In Thailand, compared with pooled real-time PCR, RealAmp demonstrated 100% sensitivity (95% CI, 59.0%-100%) and 96.7% specificity (95% CI, 91.7%-99.1%). Testing at the health center demonstrated RealAmp's potential to serve as a point-of-care test with results available in 30-75 minutes. CONCLUSION: RealAmp was comparable to PCR in detecting malaria parasites and shows promise as a tool to detect submicroscopic infections in malaria control and elimination programs worldwide. |
Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites
Streatfield PK , Khan WA , Bhuiya A , Hanifi SM , Alam N , Diboulo E , Sie A , Ye M , Compaore Y , Soura AB , Bonfoh B , Jaeger F , Ngoran EK , Utzinger J , Melaku YA , Mulugeta A , Weldearegawi B , Gomez P , Jasseh M , Hodgson A , Oduro A , Welaga P , Williams J , Awini E , Binka FN , Gyapong M , Kant S , Misra P , Srivastava R , Chaudhary B , Juvekar S , Wahab A , Wilopo S , Bauni E , Mochamah G , Ndila C , Williams TN , Hamel MJ , Lindblade KA , Odhiambo FO , Slutsker L , Ezeh A , Kyobutungi C , Wamukoya M , Delaunay V , Diallo A , Douillot L , Sokhna C , Gómez-Olivé FX , Kabudula CW , Mee P , Herbst K , Mossong J , Chuc NT , Arthur SS , Sankoh OA , Tanner M , Byass P . Glob Health Action 2014 7 25369 BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology. |
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