bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Hospitalizations in Children
Authors: Yildirim Inci , Kao Carol M , Tippett Ashley , Suntarattiwong Piyarat , Munye Mohamed , Yi Jumi , Elmontser Mohnd , Quincer Elizabeth , Focht Chris , Watson Nora , Bilen Hande , Baker Julia M , Lopman Ben , Hogenesch Elena , Rostad Christina A , Anderson Evan J 
Published: August 2021

Abstract

Background
Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains.

Methods
We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months–17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012–2013 to 2016–2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 – adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates.

Results
We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7–10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012–2013 to 2016–2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B.

Conclusions
Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by &gt;50% across 5 influenza seasons.
Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization
Authors: Fintzi Jonathan , Bonnett Tyler , Sweeney Daniel A , Huprikar Nikhil A , Ganesan Anuradha , Frank Maria G , McLellan Susan L F , Dodd Lori E , Tebas Pablo , Mehta Aneesh K 
Published: August 2021

Abstract

Background
The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death.

Methods
We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient’s clinical course to characterize the effect of remdesivir on progression along the 4 pathways above.

Results
Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio [HR], 0.73; 95% confidence interval [CI]: .59–.91) and increased clinical improvement (HR, 1.22; 95% CI: 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (HR, 0.74; 95% CI: .57–.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (HR, 0.73; 95% CI: .53–1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline.

Conclusions
Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.
Incidence and Clinical Characteristics of and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Pregnant Individuals in the United States
Authors: Dawood Fatimah S , Varner Michael , Tita Alan , Newes-Adeyi Gabriella , Gyamfi-Bannerman Cynthia , Battarbee Ashley , Bruno Ann , Daugherty Michael , Reichle Lawrence , Vorwaller Kelly , Vargas Celibell , Parks Mickey , Powers Emily , Lucca-Susana Miriam , Gibson Marie , Subramaniam Akila , Cheng Yiling J , Feng Pei-Jean , Ellington Sascha , Galang Romeo R , Meece Jennifer , Flygare Chris , Stockwell Melissa S 
Published: August 2021

Abstract

Background
Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population.

Methods
We prospectively followed a cohort of pregnant individuals during August 2020–March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription–polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)–like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated.

Results
Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7–14.3) person-weeks for any infection, 5.7 per 1000 (1.7–9.7) for symptomatic infections, and 3.5 per 1000 (0–7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6–16) days.

Conclusions
Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community.
Post-Vaccination Coronavirus Disease 2019: A Case-Control Study and Genomic Analysis of 119 Breakthrough Infections in Partially Vaccinated Individuals
Authors: Baltas Ioannis , Boshier Florencia A T , Williams Charlotte A , Bayzid Nadua , Cotic Marius , Afonso Guerra-Assunção José , Irish-Tavares Dianne , Haque Tanzina , Hart Jennifer , Roy Sunando , Williams Rachel , Breuer Judith , Mahungu Tabitha W 
Published: August 2021

Abstract

Background
Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic.

Methods
We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020–March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed.

Results
Overall, 116 of 119 cases developed COVID-19 post–first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P &lt; .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (–1.89 days; 95% CI: –4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage).

Conclusions
Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.
Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria
Authors: Schmitt Esther K , Ndayisaba Gilles , Yeka Adoke , Asante Kwaku Poku , Grobusch Martin P , Karita Etienne , Mugerwa Henry , Asiimwe Stephen , Oduro Abraham , Fofana Bakary , Doumbia Seydou , Su Guoqin , Csermak Renner Katalin , Venishetty Vinay Kumar , Sayyed Sarfaraz , Straimer Judith , Demin Ivan , Barsainya Sarita , Boulton Caroline , Gandhi Preetam 
Published: August 2021

Abstract

Background
Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere).

Methods
This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)–corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed.

Results
All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was &gt;75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional.

Conclusions
Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of &gt;65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner.

Clinical Trials Registration
ClinicalTrials.gov (NCT03334747).
Clinical Spectrum of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Protection From Symptomatic Reinfection
Authors: Maier Hannah E , Kuan Guillermina , Saborio Saira , Carrillo Fausto Andres Bustos , Plazaola Miguel , Barilla Carlos , Sanchez Nery , Lopez Roger , Smith Matt , Kubale John , Ojeda Sergio , Zuniga-Moya Julio C , Carlson Bradley , Lopez Brenda , Gajewski Anna M , Chowdhury Mahboob , Harris Eva , Balmaseda Angel , Gordon Aubree 
Published: August 2021

Abstract

Background
There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings.

Methods
We followed 2338 people in Managua, Nicaragua, aged &lt;94 years from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay. Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection.

Results
There was a large epidemic that peaked between March and August 2020. In total, 129 RT-PCR–positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% confidence interval [CI], 4.4–6.3). Seroprevalence was 56.7% (95% CI, 53.5%–60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were 2 deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2–seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic reinfection (95% CI, 51.1%–99.2%).

Conclusions
This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic reinfection.
Evidence reversals in primary care research: a study of randomized controlled trials
Authors: Ruchon Christian , Grad Roland , Ebell Mark H , Slawson David C , Pluye Pierre , Filion Kristian B , Rousseau Mathieu , Braschi Emelie , Sridhar Soumya , Grover-Wenk Anupriya , Cheung Jennifer Ren-Si , Shaughnessy Allen F 
Published: August 2021

Abstract

Background
Evidence-Based Medicine is built on the premise that clinicians can be more confident when their decisions are grounded in high-quality evidence. Furthermore, evidence from studies involving patient-oriented outcomes is preferred when making decisions about tests or treatments. Ideally, the findings of relevant and valid trials should be stable over time, that is, unlikely to be reversed in subsequent research.

Objective
To evaluate the stability of evidence from trials relevant to primary healthcare and to identify study characteristics associated with their reversal.

Methods
We studied synopses of randomized controlled trials (RCTs) published from 2002 to 2005 as “Daily POEMs” (Patient Oriented Evidence that Matters). The initial evidence (E1) from these POEMs (2002–2005) was compared with the updated evidence (E2) on that same topic in a summary resource (DynaMed 2019). Two physician-raters independently categorized each POEM-RCT as (i) reversed when E1 ≠ E2, or as (ii) not reversed, when E1 = E2. For all “Evidence Reversals” (E1 ≠ E2), we assessed the direction of change in the evidence.

Results
We evaluated 408 POEMs on RCTs. Of those, 35 (9%; 95% confidence interval [6–12]) were identified as reversed, 359 (88%) were identified as not reversed, and 14 (3%) were indeterminate. On average, this represents about 2 evidence reversals per annum for POEMs about RCTs.

Conclusions
Over 12–17 years, 9% of RCTs summarized as POEMs are reversed. Information alerting services that apply strict criteria for relevance and validity of clinical information are likely to identify RCTs whose findings are stable over time.
Identifying hot spots for harm and blind spots across the care pathway from patient complaints about general practice
Authors: O’Dowd Emily , Lydon Sinéad , Lambe Kathryn , Rudland Chris , Hilton Aoife , O’Connor Paul 
Published: August 2021

Abstract

Introduction
Healthcare complaints are underutilized for quality improvement in general practice. Systematic analysis of complaints has identified hot spots (areas across the care pathway where issues occur frequently) and blind spots (areas across the care pathway that cannot be observed by staff) in secondary care. The Healthcare Complaints Analysis Tool (HCAT) has been adapted to the HCAT(GP).

Aims
This study aimed to: (i) assess whether the HCAT(GP) can systematically analyze complaints about general practice; and (ii) identify hot spots and blind spots in general practice.

Methods
GP complaints were sampled. Complaints were coded with the HCAT(GP), classified by HCAT(GP) category (e.g. Safety, Environment, Listening), stage of care (e.g. accessing care, referral/follow-up), severity (e.g. low, medium, high), and harm (e.g. none, major). Descriptive statistics were run to identify discrete issues. A chi-square test of independence identified hot spots, and logistic regression was used for blind spots.

Results
A total of 230 complaints, encompassing 432 issues (i.e. unique problems within complaints), were categorized. Relationship issues (e.g. problems with listening, communication, and patient rights) emerged most frequently (n = 174, 40%). Hot spots were identified in the consultation and the referral/follow-up stages (χ 2(5, n = 432) = 17.931, P &lt; 0.05). A blind spot for multiple issues was identified, with the likelihood of harm increasing with number of issues (odds ratio = 2.02, confidence interval = 1.27–3.23, P &lt; 0.05).

Conclusions
Complaints are valuable data for improving general practice. This study demonstrated that the HCAT(GP) can support the systematic analysis of general practice complaints, and identify hot spots and blind spots in care.
Revising while playing: development and evaluation of the newly created Microbial Pursuit game as a pedagogical tool in higher education
Authors: Murillo Isabel 
Published: August 2021

ABSTRACTPlaying games is an invaluable and widely used educational tool in both primary and secondary schools and there is an increasing interest in building games into the curricula in the higher education system. This project involves the creation and playing of a board game with questions on a science discipline. Questions and answers are collaboratively made by the students based on the unit material. It is therefore in both the making and the playing of the game that learning takes place. The game contains not only a collaborative element but also an element of competitiveness as the students play with and against their colleagues. Both these elements are designed with the intention of enhancing student engagement with the topic of microbiology. The game, called Microbial Pursuit, represents a versatile tool for converting tutorials and workshops into pedagogical and enjoyable sessions, as well as a promising unit revision tool.
Canadian Exclusion Jurisprudence post-Febles
Authors: Joeck Molly 
Published: August 2021

Abstract
This article examines the state of Canadian refugee law since the decision of the Supreme Court in Febles v Canada (Citizenship and Immigration) [2014] 3 SCR 431. Drawing upon an analysis of a set of decisions of the Immigration and Refugee Board, the administrative tribunal tasked with refugee status determination in Canada, the article seeks to determine whether administrative decision makers are heeding the guidance of Febles when excluding asylum seekers from refugee protection on the basis of serious criminality pursuant to article 1F(b) of the 1951 Convention relating to the Status of Refugees. In doing so, it examines the controversy around article 1F(b) since its inception across various jurisdictions and amongst academic commentators, situating Febles within that controversy in order to demonstrate that the Supreme Court’s reluctance to clearly set out the purpose underlying article 1F(b) is in step with a longstanding tendency to understand the provision as serving a gatekeeping function, that prevents criminalized non-citizens from obtaining membership in our society. It argues that by omitting to set out a clear and principled standard by which asylum seekers can be excluded from refugee protection pursuant to article 1F(b), the Supreme Court failed to live up to a thick understanding of the rule of law. It concludes by calling for a reassertion of the rule of law into exclusion decision making, both nationally and internationally, in order to ensure that the legitimacy of the international refugee law regime is maintained.
Fully oral targeted antibiotic therapy for Gram-positive cocci-related periprosthetic joint infections: a real-life before and after study
Authors: Coehlo Alexandre , Robineau Olivier , Titecat Marie , Blondiaux Nicolas , Dezeque Hervé , Patoz Pierre , Loiez Caroline , Putman Sophie , Beltrand Eric , Migaud Henri , Senneville Eric 
Published: August 2021

Abstract

Background
The optimal length of the intravenous antibiotic treatment of periprosthetic joint infections (PJIs) generally ranges from one to six weeks and is a matter of debate. Most antibiotics active against Gram-positive cocci (GPC) exhibit both high oral bioavailability and bone diffusion. Thus, early oral therapy may be a reasonable option in GPC-related PJIs.

Methods
A 2 year before and after monocentric study that aimed to compare two antibiotic strategies. Empirical intravenous postoperative antibiotic treatment was followed by 7 to 10 days of intravenous targeted therapy (‘before’ group) or by full orally targeted antibiotic treatment (‘after’ group). The primary outcome was a treatment failure during follow-up.

Results
A total of 93 patients were analysed, 43 and 50 in the before and the after groups, respectively. Both groups were comparable in terms of surgical procedures, comorbidities, microbiological documentation and infection site. Antibiotics prescribed to our patients had high oral bioavailability and bone diffusion with rifampicin/fluoroquinolone combinations being the most frequent antibiotic regimens. Both hospital stay and intravenous antibiotic treatment mean durations were shorter in the before group than in the after group [15.0 versus 11.0 days; (P &lt; 0.01) and 13.0 versus 7.0 days; P &lt; 0.001, respectively]. The remission rate assessed after at least a year of follow-up was comparable in the before and the after groups (hazard ratio = 0.70; 95% CI 0.30–1.58).

Conclusions
Full oral targeted antibiotic therapy using a drug regimen with high oral bioavailability and good bone diffusion is an option for the treatment of patients with GPC-related PJIs.