scholarly journals Comparative longitudinal variation of total, IgG and IgA anti-SARS-CoV-2 antibodies in recipients of BNT162b2 vaccination

2021 ◽  
Author(s):  
Gian Luca Salvagno ◽  
Brandon M. Henry ◽  
Laura Pighi ◽  
Simone De Nitto ◽  
Gianluca Gianfilippi ◽  
...  
Keyword(s):  
Median Time ◽  
Individual Variation ◽  
Longitudinal Variation ◽  
Considerable Decrease ◽  
Vast Array ◽  
Study Population ◽  
Healthcare Employees

Abstract Background: This article aims to summarize the 6-month variation of a vast array of anti-SARS-CoV-2 antibodies in recipients of BNT162b2 mRNA-based vaccination.Methods: The study population consisted of 84 baseline SARS-CoV-2 seronegative healthcare employees (median age 45 years, 53.6% females), receiving mRNA-based BNT162b2 vaccination. Blood was collected before the first and second BNT162b2 vaccine doses, as well as 1, 3 and 6 months afterwards. The serum titers of the following anti-SARS-CoV-2 antibodies were assayed: total anti-RBD, anti-spike trimeric IgG, anti-RBD IgG and anti-spike S1 IgA.Results: All antibodies levels peaked 1 month after vaccination, but then displayed a considerable decrease. The median rates of 6-month decline were -95% for IgG anti-SARS-CoV-2 RBD, -85% for IgG anti-SARS-CoV-2 trimeric spike, -73% for IgA anti-SARS-CoV-2 S1 and -56% for total anti-SARS-CoV-2 RBD antibodies, respectively. The median time of seronegativization was estimated at 579 days for total anti-SARS-CoV-2 RBD antibodies, 271 days for IgG anti-SARS-CoV-2 trimeric spike, 264 days for IgG anti-SARS-CoV-2 RBD and 208 days for IgA anti-SARS-CoV-2 S1, respectively. The rate of seropositive subjects declined from 98-100% at the peak to 50-100% after 6 months. The inter-individual variation of anti-SARS-CoV-2 antibodies reduction at 6 months was 3-44% from the peak.Conclusions: The results of this longitudinal serosurvey demonstrate that the titer of anti-SARS-CoV-2 antibodies declined 6 months after BNT162b2 vaccination, with median time of IgG/IgA seronegativization estimated between 7-9 months, thus supporting the opportunity of administering vaccine boosters approximately 6 months after the last dose.

scholarly journals Comparative longitudinal variation of total IgG and IgA anti-SARS-CoV-2 antibodies in recipients of BNT162b2 vaccination

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Giuseppe Lippi ◽  
Gian Luca Salvagno ◽  
Brandon M. Henry ◽  
Laura Pighi ◽  
Simone De Nitto ◽  
...  
Keyword(s):  
Median Time ◽  
Receptor Binding ◽  
Individual Variation ◽  
Primary Vaccination ◽  
Binding Domain ◽  
Longitudinal Variation ◽  
Receptor Binding Domain ◽  
Considerable Decrease ◽  
Vast Array ◽  
Study Population

Abstract Objectives This article aims to summarize the 6-month variation of a vast array of anti-SARS-CoV-2 antibodies in recipients of BNT162b2 mRNA-based vaccination. Methods The study population consisted of 84 baseline SARS-CoV-2 seronegative healthcare employees (median age 45 years, 53.6% females), receiving mRNA-based BNT162b2 primary vaccination cycle. Blood was collected before the first and second BNT162b2 vaccine doses, as well as 1, 3 and 6 months afterwards. The serum titers of the following anti-SARS-CoV-2 antibodies were assayed: total anti-RBD (receptor binding domain), anti-spike trimeric IgG, anti-RBD IgG and anti-spike S1 IgA. Results All antibodies’ levels peaked 1 month after vaccination, but then displayed a considerable decrease. The median rates of 6-month decline were −95% for IgG anti-SARS-CoV-2 RBD, −85% for IgG anti-SARS-CoV-2 trimeric spike, −73% for IgA anti-SARS-CoV-2 S1 and −56% for total anti-SARS-CoV-2 RBD antibodies, respectively. The median time of seronegativization was estimated at 579 days for total anti-SARS-CoV-2 RBD antibodies, 271 days for IgG anti-SARS-CoV-2 trimeric spike, 264 days for IgG anti-SARS-CoV-2 RBD and 208 days for IgA anti-SARS-CoV-2 S1, respectively. The rate of seropositive subjects declined from 98–100% at the peak to 50–100% after 6 months. The inter-individual variation of anti-SARS-CoV-2 antibodies reduction at 6 months was 3–44% from the peak. Conclusions The results of this longitudinal serosurvey demonstrate that the titer of anti-SARS-CoV-2 antibodies declined 6 months after BNT162b2 vaccination, with median time of IgG/IgA seronegativization estimated between 7 and 9 months, thus supporting the opportunity of administering vaccine boosters approximately 5 to 6 months after the last dose of the primary vaccination cycle.

Progression rates and sample size estimates for PPMS based on the CLIMB study population

2014 ◽  
Vol 21 (2) ◽  
pp. 180-188 ◽  
Author(s):  
Kesav Raghavan ◽  
Brian C Healy ◽  
Robert L Carruthers ◽  
Tanuja Chitnis
Keyword(s):  
Median Time ◽  
Trial Design ◽  
Age Of Onset ◽  
Clinical Trial Design ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Interval Censored ◽  
Study Population ◽  
Size Estimates

Background: The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts. Objective: The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression. Methods: We studied PPMS ( n = 73) and relapsing-onset MS (ROMS) patients ( n = 1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women’s Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression. Results: The PP group had a 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4±9.6; RO: 32.7±9.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS ( p < 0.001). Median time from onset to EDSS 6.0 was faster in PPMS ( p < 0.001). PPMS patients progressed faster to EDSS 3 ( p < 0.001) and from EDSS 3 to 6 ( p < 0.001). Median time to sustained progression in the PP group was 4.85 years (95% CI 2.83–8.35), significantly faster than the RO group ( p < 0.001). Conclusions: Our modern PPMS cohort is demographically similar to previously studied cohorts. PPMS is associated with faster disability accrual than ROMS. Current real-world observations of time to sustained progression will inform design of new clinical trials for PPMS.

Abstract W P65: Clevidipine Outperforms Other Agents in Emergent Acute Hypertension Treatment in Ischemic Stroke Pre-rt-PA

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Scott S Brehaut ◽  
Angelina M Roche
Keyword(s):  
Ischemic Stroke ◽  
Median Time ◽  
Pressure Control ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Hypertension Treatment ◽  
Stroke Patients ◽  
First Line ◽  
Acute Hypertension ◽  
Study Population

Hypothesis: Minimizing Acute Hypertension Treatment (AHT) time in rt-PA candidates is one means to reduce door to needle times. We have used nicardipine, labetalol and clevidipine at our institution for treatment of ischemic stroke patients in the ED. We assessed the hypothesis that if one agent could be identified that safely outperformed others, door to blood pressure control times could be improved in patients otherwise eligible for rt-PA. Methods: We evaluated all ischemic stroke ED patients receiving rt-PA at our institution from 1/1/07 - 1/31/14; data from ischemic stroke patients requiring AHT prior to administration of rt-PA were analyzed by agent. Results: Two hundred thirty two patients received rt-PA; 32 (14%) required AHT. Diagnoses: Unspecified Cerebral Occlusion, 21 (9%); Embolic Ischemic Stroke, 8 (3%); Thrombotic Ischemic Stroke, 1 (<1%); Vertebral Artery Occlusion Ischemic Stroke, 1 (<1%); Carotid Artery Occlusion Ischemic Stroke, 1 (<1%). Data were analyzed by agent. Five patients were excluded due to limited BP documentation; 12 patients received labetalol, 10 patients received clevidipine, and 2 patients received nicardipine. Three additional patients failed labetalol and were switched to clevidipine. Median time from drug initiation to BP goal (MTG) and median elapsed times from door to rt-PA administration (MET) were calculated. MTG and MET were: Labetalol: 43 minutes (range 5 to 83) and 97.5 minutes (range 57 to 127); Clevidipine: 16 minutes (range 6 to 24) and 54 minutes (range 50 to 120); Nicardipine: 30.5 minutes (range 5 to 56) and 113 minutes (range 102 to 124). Clevidipine Rescued MTG: 11 minutes (range 10 to 30). AHT volume administered, median (range): Labetalol 15 ml (5-40); Nicardipine 30.4 ml (16-44.8); and Clevidipine 1.8 ml (0.7-8.6). Conclusions: In conclusion we found of AHT drugs prescribed in this study population, clevidipine demonstrated the shortest median time-to-BP control, the shortest median door-to-rt-PA administration and the lowest administered volume. On the basis of these data, clevidipine is now first line AHT for rt-PA candidates at our institution. The study is ongoing.

scholarly journals Universal method for robust detection of circadian state from gene expression

2018 ◽  
Vol 115 (39) ◽  
pp. E9247-E9256 ◽  
Author(s):  
Rosemary Braun ◽  
William L. Kath ◽  
Marta Iwanaszko ◽  
Elzbieta Kula-Eversole ◽  
Sabra M. Abbott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Universal Method ◽  
Biological Processes ◽  
Accurate Assessment ◽  
Delivery Time ◽  
Vast Array ◽  
Robust Detection ◽  
Circadian Time ◽  
Study Population ◽  
Transcriptional Biomarkers

Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burdensome to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here, we introduce TimeSignature, an algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using distinct microarrays and further validate it against a new set of samples profiled by RNA-sequencing. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2 h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique among expression-based predictors and addresses a major challenge in the development of generalizable, clinically useful tests.

Immune checkpoint inhibitor (ICI)-related pneumonitis among patients with lung cancer admitted to an Oncology Hospitalist Service: Treatment patterns and hospitalization outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21054-e21054
Author(s):  
Hadeel Neamat Sahar ◽  
Jeffrey Aldrich ◽  
Christine B. Peterson ◽  
Norman Brito-Dellan ◽  
Maggie Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mortality Rate ◽  
Median Time ◽  
Immune Checkpoint ◽  
Readmission Rate ◽  
Treatment Patterns ◽  
Comprehensive Cancer Center ◽  
Study Population ◽  
The Mean ◽  
Grade 3

e21054 Background: Immune checkpoint inhibitors (ICI) have gained success in the treatment of multiple malignancies including lung cancer. However, immune-related adverse events (irAE) are common with pneumonitis being one of the most fatal having a 10% mortality rate. As such, early identification and treatment of irAEs are important. We describe the treatment patterns and hospitalization outcomes of patients with lung cancer with grade ≥3 ICI-related pneumonitis (ICI-P) admitted to an oncology hospitalist service at a comprehensive cancer center. Methods: We performed a retrospective review of patients with lung cancer admitted to our oncology hospitalist service with a suspicion of ICI-P between January 1, 2019 and November 30, 2019. ICI-P was confirmed if the patient received irAE-specific management, or if there was multidisciplinary consensus among treating providers. Descriptive statistics were utilized. Here we present the demographic and clinical characteristics of the study population as well as hospitalization outcomes. Results: We identified 49 patients with lung cancer who received at least one dose of ICI before being admitted with a suspicion of ICI-P. The mean age was 67y, with 63% being male and 86% having a diagnosis of non-small cell lung cancer. The most common ICI received by patients was pembrolizumab (67%). 84% were on active ICI treatment at the time of hospitalization and the median time from the 1st ICI dose to hospitalization was 3.5 months. Pulmonology was consulted in 88% of patients. Only 63% (n=31) of those admitted with a suspicion of ICI-P were confirmed to have ICI-P. The mean time to first ICI-P directed treatment was 2.2 days from admission with all 31 patients receiving corticosteroids. 23% required infliximab and 10% required IVIG. Patients with confirmed ICI-P had a median length of stay of 8 days, with 19% requiring ICU stay. The ICI-P inpatient mortality rate was 32%. Of those discharged alive (n=21), 90% were discharged on oral corticosteroids. GI and PJP prophylaxis were prescribed for 95% and 81% of the discharged patients, respectively. The 30-day readmission rate for this subgroup was 29%. 86% were seen by their oncologist within a median time of 8 days from discharge. Conclusions: Studies have shown that patients with grade ≥3 ICI-related pneumonitis (i.e. requiring hospitalization) have high mortality rates and this was consistent with our findings. Treatment for ICI-related pneumonitis was started >2 days from admission in our study population. A high index of suspicion is necessary to expedite work-up, and a multidisciplinary approach is key to confirm diagnosis and promptly initiate treatment. Readmission rate was high. Care coordination and strategies for safe transitions of care at discharge should be ensured to improve the overall outcome.

scholarly journals Adherence and Associated Factors of Treatment Regimen in Drug-Susceptible Tuberculosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Sungho Bea ◽  
Hyesung Lee ◽  
Ju Hwan Kim ◽  
Seung Hun Jang ◽  
Hyunjin Son ◽  
...  
Keyword(s):  
Median Time ◽  
Healthcare Providers ◽  
Healthcare Database ◽  
Factors Associated ◽  
Kaplan Meier ◽  
History Of ◽  
Study Population ◽  
Triple Regimen ◽  
Key Aspects

Background: Adherence to tuberculosis (TB) drugs is one of the key aspects of global TB control, yet there is a lack of epidemiological evidence on the factors influencing adherence to TB drugs. Thus, this study aimed to explore the adherence and factors associated with adherence among TB patients in South Korea.Methods: We conducted a cohort study using a sampled national healthcare database from 2017 to 2018. Our study population included incident TB patients initiating quadruple or triple regimen who were available for follow-up for 180-days. Adherence was evaluated using the proportion of days covered (PDC): 1) adherent group: patients with PDC ≥80%; 2) non-adherent group: patients with PDC &lt;80%. Kaplan-Meier analysis was conducted to calculate the median time-to-discontinuation in the study population. We calculated the adjusted odds ratios (aOR) with 95% confidence intervals (CI) to assess factors associated with adherence to TB drugs using logistic regression.Results: Of 987 patients, 558 (56.5%) were adherent and 429 (43.5%) were non-adherent, with the overall mean PDC of 68.87% (standard deviation, 33.37%). The median time-to-discontinuation was 113 days (interquartile range 96–136) in the study population. Patients initiating quadruple regimen were more likely to adhere in comparison to the triple regimen (aOR 4.14; 95% CI 2.78–6.17), while those aged ≥65 years (aOR 0.53; 95% CI 0.35–0.81), with a history of dementia (aOR 0.53; 95% CI 0.34–0.85), and with history of diabetes mellitus (aOR 0.70; 95% CI 0.52–0.96) were less likely to adhere to the drug.Conclusion: Approximately 45% of TB patients were non-adherent to the drug, which is a major concern for the treatment outcome. We call for intensified attention from the authorities and healthcare providers to reinforce patients’ adherence to the prescribed TB drugs.

scholarly journals Nest ornaments and feather composition form an extended phenotype syndrome in a wild bird

2020 ◽  
Vol 74 (11) ◽  
Author(s):  
Pauliina Järvinen ◽  
Jon E. Brommer
Keyword(s):  
Individual Variation ◽  
Bird Species ◽  
The Other ◽  
Correlated Response ◽  
Nest Construction ◽  
Extended Phenotype ◽  
Lining Material ◽  
Study Population ◽  
Avian Nest ◽  
Blue Tits

Abstract Many species throughout the animal kingdom construct nests for reproduction. A nest is an extended phenotype—a non-bodily attribute—of the individual building it. In some bird species, including our study population of blue tits (Cyanistes caeruleus), conspicuous feathers or other material are placed on top of the nest. These so-called nest ornaments do not contribute to nest insulation, but are hypothesised to have a signalling function. Here, we apply the concept of behavioural syndromes, with focus on between-individual variation (repeatability) and between-individual correlations, to the study of avian nest construction. We find that nest ornamentation is a moderately repeatable trait in female blue tits, which suggests it is an extended phenotype of the female. Furthermore, the tendency to ornament the nest covaries across females with another aspect of her extended phenotype, the composition of the nest lining material, and these two traits thus form an extended phenotype syndrome. Assuming the correlation is reflected on a genetic level, it implies that nest ornamentation and composition of the nest lining do not evolve in isolation; one aspect may be an evolutionary by-product of selection on the other aspect and their overall flexibility to respond to change is reduced. Significance statement The avian nest is an extended phenotype (a non-bodily attribute) of its builder with potentially multiple functions in terms of insulation and signalling. In particular, many bird species’ nests contain nest ornaments, feathers or other materials that are placed on top of the nest and that stand out from the nest material due to their colour and/or size. We quantified between-individual variation (repeatability) of nest ornamentation behaviour in a wild population of blue tits and between-individual covariation (syndrome) of nest ornamentation to other features of nest construction. We find that nest ornamentation is a repeatable trait limited to females in our study population. The tendency to ornament the nest covaries across females with another aspect of her extended nest phenotype, the composition of the nest lining material. These correlated traits thus form an extended phenotype syndrome. It hence becomes crucial to recognise that a study of a single aspect of nest construction in isolation captures only a part of the complexity, as one aspect may have evolved as a correlated response of selection on the other aspect. Moreover, such a syndrome implies limited flexibility in the range of adaptive response.

The challenge of accounting for individual differences in folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Benjamin C. Ruisch ◽  
Rajen A. Anderson ◽  
David A. Pizarro
Keyword(s):  
Individual Differences ◽  
Individual Variation ◽  
Political Ideologies ◽  
Economic Beliefs ◽  
Existing Data

AbstractWe argue that existing data on folk-economic beliefs (FEBs) present challenges to Boyer & Petersen's model. Specifically, the widespread individual variation in endorsement of FEBs casts doubt on the claim that humans are evolutionarily predisposed towards particular economic beliefs. Additionally, the authors' model cannot account for the systematic covariance between certain FEBs, such as those observed in distinct political ideologies.

Inter-individual variation shapes the human microbiome

2019 ◽  
Vol 42 ◽  
Author(s):  
Emily F. Wissel ◽  
Leigh K. Smith
Keyword(s):  
Individual Differences ◽  
Individual Variation ◽  
Human Microbiome ◽  
Individual Variability ◽  
Microbiota Composition ◽  
Target Article ◽  
Microbiome Research

Abstract The target article suggests inter-individual variability is a weakness of microbiota-gut-brain (MGB) research, but we discuss why it is actually a strength. We comment on how accounting for individual differences can help researchers systematically understand the observed variance in microbiota composition, interpret null findings, and potentially improve the efficacy of therapeutic treatments in future clinical microbiome research.

Cell morphology, volume, and surface area determinations from multilevel contouring within HVEM micrographs of serial sections and whole-cell mounts

1987 ◽  
Vol 45 ◽  
pp. 588-589
Author(s):  
M. Marko ◽  
A. Leith ◽  
D. Parsons
Keyword(s):  
Surface Area ◽  
Electron Micrographs ◽  
Cell Morphology ◽  
Individual Variation ◽  
Serial Section ◽  
Stereo Pair ◽  
Complex Structures ◽  
Serial Sections ◽  
Surface Areas ◽  
Computer Based

The use of serial sections and computer-based 3-D reconstruction techniques affords an opportunity not only to visualize the shape and distribution of the structures being studied, but also to determine their volumes and surface areas. Up until now, this has been done using serial ultrathin sections.The serial-section approach differs from the stereo logical methods of Weibel in that it is based on the Information from a set of single, complete cells (or organelles) rather than on a random 2-dimensional sampling of a population of cells. Because of this, it can more easily provide absolute values of volume and surface area, especially for highly-complex structures. It also allows study of individual variation among the cells, and study of structures which occur only infrequently.We have developed a system for 3-D reconstruction of objects from stereo-pair electron micrographs of thick specimens.

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