Preterm birth and stillbirth during COVID-19 pandemic in Bihor County/Romania.

Background: International studies have reported conflicting data about the effects of COVID-19 pandemic policy measures on maternal and neonatal health. A major impact was reported on stillbirth and prematurity. The published literature suggests that the economic setting influenced the effects of imposed mitigation measures with a more severe effect in low-income countries. Objectives: Our objective is to compare pregnancy outcomes at the only tertiary Maternity Hospital in Bihor County-Romania before and during the COVID-19 pandemic. This study aims to observe and document differences in perinatal outcomes across these periods, without inferring direct causation related to the pandemic or its associated restrictions. Materials and methods: We used data from the registries of Public Health Services Bihor to conduct a retrospective cohort analysis of preterm births and stillbirths during the COVID-19 pandemic in Bihor County, Romania. Pregnancy outcomes were compared between the pandemic period (March 2020-February 2022) to the corresponding historical pre-COVID-19 period (March 2018-February 2020). Maternal socio-demographic variables and neonatal characteristics of these periods were also examined. Results: The COVID-19 pandemic period was associated with an increase in the stillbirth rate (RR: 1.53, 95% CI, 1.05-2.23). Preterm birth was significantly impacted during this period and showed changes when analyzing gestational age (RR: 0.88, 95% CI, 0.79-0.96) or birth weight (RR: 0.91, 95% CI, 0.82-1.00). The main cause of stillbirth was intrauterine asphyxia due to placental causes (67.6%) or cord pathology (12.6%), the most frequently encountered maternal pathology was cardiovascular (28.3%) or infectious (21.7%). Our study revealed no significant changes in terms of maternal and neonatal characteristics during the two-year pandemic period. Conclusions: Lockdown restrictions in Bihor County, Romania were associated with an increase in stillbirths, whilst preterm birth rate decreased. This raises concerns about whether pandemic policy measures may have led to a failure in identifying and offering proper care for pregnant women who were more likely to experience an antepartum loss. Further studies across the globe are needed in order to integrate comparable data that will help develop adequate protocols and policies for protecting maternal and child health during the next pandemic that will follow.

Association of Fortification with Human Milk versus Bovine Milk-Based Fortifiers on Short-Term Outcomes in Preterm Infants-A Meta-Analysis.

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Development and validation of a chemiluminescent western blot assay for glanders (Burkholderia mallei) serodetection.

Glanders, caused by Burkholderia mallei, is a zoonotic disease of equids. Serologic testing for glanders is required by disease-free countries before international movement of equids. The World Organisation for Animal Health Terrestrial Manual recommends the complement fixation test (CFT) for clearance of individual animals for movement, but the CFT is prone to false-positive results. A colorimetric western blot (WB) assay was developed and validated to resolve false-positive CFT results; however, that assay is relatively time-consuming, and the interpretation is subjective. We present here a procedurally similar chemiluminescent WB assay that performs comparably to the validated colorimetric WB assay and offers noticeable benefits of decreased time-to-result and greater ease of interpretation.

Successful expansion and cryopreservation of human natural killer cell line NK-92 for clinical manufacturing.

Natural killer (NK) cells have recently shown renewed promise as therapeutic cells for use in treating hematologic cancer indications. Despite this promise, NK cell manufacturing workflows remain largely manual, open, and disconnected, and depend on feeders, as well as outdated unit operations or processes, often utilizing research-grade reagents. Successful scale-up of NK cells critically depends on the availability and performance of nutrient-rich expansion media and cryopreservation conditions that are conducive to high cell viability and recovery post-thaw. In this paper we used Cytiva hardware and media to expand the NK92 cell line in a model process that is suitable for GMP and clinical manufacturing of NK cells. We tested a range of cryopreservation factors including cooling rate, a range of DMSO-containing and DMSO-free cryoprotectants, ice nucleation, and cell density. Higher post-thaw recovery was seen in cryobags over cryovials cooled in identical conditions, and cooling rates of 1°C/min or 2°C/min optimal for cryopreservation in DMSO-containing and DMSO-free cryoprotectants respectively. Higher cell densities of 5x107 cells/ml gave higher post-thaw viability than those cryopreserved at either 1x106 or 5x106 cells/ml. This enabled us to automate, close and connect unit operations within the workflow while demonstrating superior expansion and cryopreservation of NK92 cells. Cellular outputs and performance were conducive to clinical dosing regimens, serving as a proof-of-concept for future clinical and commercial manufacturing.

Epithelial Immune Cell Response to Initial Soft Contact Lens Wear in the Human Corneal and Conjunctival Epithelium.

Purpose: The purpose of this study was to assess the immediate ocular immune response to soft contact lens (CL) wear by examining presumed epithelial immune cell (EIC) density and morphology at the central, peripheral, limbal cornea, and conjunctiva. Methods: Fifty-four participants naïve to CL wear (mean age = 24.8 ± 9.8 years, 44% female participants), were examined using in vivo confocal microscopy at baseline and after 2 hours of CL wear (1-Day ACUVUE MOIST). Images were captured at the central, temporal far peripheral and limbal cornea, and bulbar conjunctiva. EIC density was counted manually and morphology was graded. Differences in EIC parameters pre- and post-CL wear were examined using a generalized estimating equation model with appropriate post hoc analyses. Results: After 2 hours of soft CL wear, there was a significant increase in EIC density in all regions other than the central cornea (all P < 0.001). Cell body size was significantly larger, and a higher proportion of participants exhibited EIC with long dendrites after lens wear at the central and peripheral cornea (both P < 0.001). There was a significant increase in the number of participants displaying EIC with thick dendrites at the peripheral (P = 0.04) and limbal cornea (P < 0.001) after lens wear. Conclusions: EICs were primarily recruited to the peripheral regions, whereas the central cornea shows no significant recruitment after short-term CL wear. Both central and peripheral corneas exhibited an enhanced antigen capture capacity, whereas migratory capacity was increased in the peripheral corneal regions suggesting EIC activation following a short period of CL wear.

Sex differences in socioemotional behavior and changes in ventral hippocampal transcription across aging in C57Bl/6J mice.

Socioemotional health is positively correlated with improved cognitive and physical aging. Despite known sex differences in socioemotional behaviors and the trajectory of aging, the interactive effects between sex and aging on socioemotional outcomes are poorly understood. We performed the most comprehensive assessment of sex differences in socioemotional behaviors in C57Bl/6J mice across aging to date. Compared to males, females exhibited decreased anxiety-like behavior and social preference but increased social recognition. With age, anxiety-like behavior, cued threat memory generalization, and social preference increased in both sexes. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed transcriptional neuropathology markers in the ventral hippocampus and found age-related changes in genes related to activated microglia, angiogenesis, and cytokines. Sex differences emerged in the timing, direction, and magnitude of these changes, independent of reproductive senescence in aged females. Interestingly, female-specific upregulation of autophagy-related genes correlated with age-related behavioral changes selectively in females. These novel findings reveal critical sex differences in trajectories of ventral hippocampal aging that may contribute to sex- and age-related differences in socioemotional outcomes.

Comparison of Illumina and Oxford Nanopore Technology for genome analysis of Francisella tularensis, Bacillus anthracis, and Brucella suis.

BACKGROUND: Bacterial epidemiology needs to understand the spread and dissemination of strains in a One Health context. This is important for highly pathogenic bacteria such as Bacillus anthracis, Brucella species, and Francisella tularensis. Whole genome sequencing (WGS) has paved the way for genetic marker detection and high-resolution genotyping. While such tasks are established for Illumina short-read sequencing, Oxford Nanopore Technology (ONT) long-read sequencing has yet to be evaluated for such highly pathogenic bacteria with little genomic variations between strains. In this study, three independent sequencing runs were performed using Illumina, ONT flow cell version 9.4.1, and 10.4 for six strains of each of Ba. anthracis, Br. suis and F. tularensis. Data from ONT sequencing alone, Illumina sequencing alone and two hybrid assembly approaches were compared. RESULTS: As previously shown, ONT produces ultra-long reads, while Illumina produces short reads with higher sequencing accuracy. Flow cell version 10.4 improved sequencing accuracy over version 9.4.1. The correct (sub-)species were inferred from all tested technologies, individually. Moreover, the sets of genetic markers for virulence, were almost identical for the respective species. The long reads of ONT allowed to assemble not only chromosomes of all species to near closure, but also virulence plasmids of Ba. anthracis. Assemblies based on nanopore data alone, Illumina data alone, and both hybrid assemblies correctly detected canonical (sub-)clades for Ba. anthracis and F. tularensis as well as multilocus sequence types for Br. suis. For F. tularensis, high-resolution genotyping using core-genome MLST (cgMLST) and core-genome Single-Nucleotide-Polymorphism (cgSNP) typing produced highly comparable results between data from Illumina and both ONT flow cell versions. For Ba. anthracis, only data from flow cell version 10.4 produced similar results to Illumina for both high-resolution typing methods. However, for Br. suis, high-resolution genotyping yielded larger differences comparing Illumina data to data from both ONT flow cell versions. CONCLUSIONS: In summary, combining data from ONT and Illumina for high-resolution genotyping might be feasible for F. tularensis and Ba. anthracis, but not yet for Br. suis. The ongoing improvement of nanopore technology and subsequent data analysis may facilitate high-resolution genotyping for all bacteria with highly stable genomes in future.

When Should Healthcare Workers With Coronavirus Disease 2019 (COVID-19) Return to Work? An Analysis of Follow-up Antigen Test Results After a Positive COVID Test.

A high percentage of healthcare workers (HCWs) who had met the Centers for Disease Control and Prevention criteria for returning to work 5 days after symptom onset remained positive for their return-to-work COVID-19 antigen test, suggesting continued infectiousness. Boosted HCWs were more likely to be antigen positive on their return-to-work test compared to unvaccinated HCWs, which merits further research.

Deepening Our Understanding of COVID-19 Vaccine Decision-Making amongst Healthcare Workers in Southwest Virginia, USA Using Exploratory and Confirmatory Factor Analysis.

Vaccine hesitancy amongst healthcare workers (HCWs) has been a major challenge throughout the COVID-19 pandemic. While many studies have identified HCW characteristics and specific attitudes associated with COVID-19 vaccine hesitancy, researchers are still working towards developing a holistic understanding of the psychological constructs that influence COVID-19 vaccine decision-making in this population. Between 15 March and 29 March 2021, we distributed an online survey assessing individual characteristics and vaccine-related perceptions to employees of a not-for-profit healthcare system in Southwest Virginia (N = 2459). We then performed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to describe patterns of vaccine-related thought amongst HCWs and identify latent psychometric constructs involved in vaccine decision-making. The goodness of model fit was assessed using the Tucker-Lewis Index (TLI), the Comparative Fit Index (CFI), and the Root Mean Square Error of Approximation (RMSEA). Internal consistency and reliability of each factor were assessed using Cronbach's alpha. EFA identified four latent psychometric constructs: Lack of trust in the COVID-19 vaccine; Anti-science sentiment; Adverse side-effects; and Situational risk assessment. The goodness of EFA model fit was adequate (TLI > 0.90, RMSEA ≤ 0.08) with acceptable internal consistency and reliability for three of four factors (Cronbach's alpha > 0.70). The CFA model also had adequate goodness of fit (CFI > 0.90, RMSEA ≤ 0.08). We believe the psychometric constructs identified in this study can provide a useful framework for interventions to improve vaccine uptake amongst this critical population.

When should healthcare workers with COVID-19 return to work? An analysis of follow-up antigen test results after a positive COVID test

BackgroundUnder CDCs guidance for mitigating healthcare worker (HCW) staffing shortages, COVID-positive HCW may return to work as early as five days after their initial positive test without a negative antigen test, if symptoms are improving. Recent studies suggest a robust correlation between a positive COVID-19 antigen test and infectiousness. MethodsFrom January to June 2022, HCW employed by a large health system who tested positive for COVID on a PCR test were instructed to isolate and return for a rapid antigen test on day 5 or later if they had been fever-free for 24 hours and their symptoms were improving. We conducted chi-squared tests and a multivariate logistic regression to assess the association between demographic characteristics, vaccination status, and days from the initial positive PCR test on RTW antigen test results. ResultsCompared to day 5, HCW had a lower odds of a positive antigen result on day 7 (OR: 0.39, p<0.0001) and after at least 8 days (OR: 0.16, p<0.0001). Unexpectedly, a positive antigen result was more likely among HCW who were vaccinated (OR: 1.41, p <0.05), boosted for more than 90 days prior (OR: 2.21, p<0.0001), and boosted within 90 days (OR: 2.08, p < 0.01) compared to not being vaccinated. ConclusionsOur findings suggest that HCW returning to work before day 7 following a positive PCR test may still be infectious and future guidelines addressing contingency staffing should reflect these findings in order to minimize possible transmission in the healthcare setting. The finding that boosted individuals had over twice the odds of returning positive on the follow up antigen test compared to unvaccinated HCWs merits additional research.

Examining drivers of coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare workers.

OBJECTIVE: To assess characteristics and perceptions associated with vaccine hesitancy among healthcare workers to increase coronavirus disease 2019 (COVID-19) vaccine uptake in this population. DESIGN: Cross-sectional quantitative survey. SETTING: A not-for-profit healthcare system in southwestern Virginia. PARTICIPANTS: A convenience sample of 2,720 employees of a not-for-profit healthcare system. METHODS: Between March 15 and 29, 2021, we conducted an Internet-based survey. Our questionnaire assessed sociodemographic and work-related characteristics, vaccine experience and intentions, agreement with vaccine-related perceptions, the most important reasons for getting or not getting vaccinated, and trusted sources of information about COVID-19. We used χ2 analyses to assess the relationship between vaccine hesitancy and both HCW characteristics and vaccine-related perceptions. RESULTS: Overall, 18% of respondents were classified as vaccine hesitant. Characteristics significantly associated with hesitancy included Black race, younger age, not having a high-risk household member, and prior personal experience with COVID-19 illness. Vaccine hesitancy was also significantly associated with many vaccine-related perceptions, including concerns about short-term and long-term side effects and a belief that the vaccines are not effective. Among vaccine-acceptant participants, wanting to protect others and wanting to help end the pandemic were the most common reasons for getting vaccinated. Personal physicians were cited most frequently as trusted sources of information about COVID-19 among both vaccine-hesitant and vaccine-acceptant respondents. CONCLUSIONS: Educational interventions to decrease vaccine hesitancy among healthcare workers should focus on alleviating safety concerns, emphasizing vaccine efficacy, and appealing to a sense of duty. Such interventions should target younger adult audiences. Personal physicians may also be an effective avenue for reducing hesitancy among their patients through patient-centered discussions.

Predictive factors of radioiodine therapy failure in Graves' Disease: A meta-analysis.

BACKGROUND: I-131 therapy is a common treatment modality for adults with Graves' Disease (GD). Utilizing meta-analysis, we examined patient specific factors that predict I-131 therapy failure. METHODS: Literature search followed PRISMA. Comprehensive Meta-analysis (version 3.0) was used. Mantel-Haenszel test with accompanying risk ratio and confidence intervals evaluated categorical variables. Continuous data was analyzed using inverse variance testing yielding mean difference or standardized mean difference. Decision tree algorithms identified variables of high discriminative performance. RESULTS: 4822 collective patients across 18 studies were included. Male sex (RR = 1.23, 95%CI = 1.08-1.41, p = 0.002), I-131 therapy 6 months after GD diagnosis (RR = 2.10, 95%CI = 1.45-3.04, p < 0.001) and history of anti-thyroid drugs (RR = 2.05, 95%CI = 1.49-2.81, p < 0.001) increased the risk of I-131 therapy failure. Elevated free thyroxine, 24-h radioactive iodine uptake scan ≥60.26% and thyroid volume ≥35.77 mL were also associated with failure. CONCLUSION: Patient characteristics can predict the likelihood of I-131 therapy failure in GD. Definitive surgical treatment may be a reasonable option for those patients.

Breast papillomas in the United States: single institution data on underrepresented minorities with a multi-institutional update on incidence.

PURPOSE: To assess the percentage of papillomas from all biopsies performed, comparing differences in patient age and race at a single institution. To assess trends in biopsied papillomas at institutions throughout the United States (US). METHODS: This is a HIPPA-compliant IRB-approved single-institution (Southern1) retrospective review to assess race and age of all-modality-biopsied non-malignant papillomas as a percentage of all biopsies (percentage papillomas calculated as papilloma biopsies/all biopsies) from January 2012 to December 2019. To assess national variation, several academic or large referral centers were contacted to provide data regarding papilloma percentages, biopsy modalities, and trends in case numbers. Trends were estimated using the method of analysis of variance (ANOVA). Comparisons of differences in trends were assessed. RESULTS: Southern1 institution demonstrated a significant association between race and percentage of papillomas (p < 0.0001). After adjustment for multiple comparisons with Bonferroni correction at 5% type I family error, the percentage of biopsied papillomas in Black and Asian patients remained significantly higher than in White patients (p < 0.0001 and p = 0.0032, respectively) using a Chi-square test. The regional variation in percentage of papillomas was found to be 3-9%. Southern1 institution showed a 7-year significant trend of increase in percentage of papillomas. Other institutions showed a decreasing trend (p < 0.05). CONCLUSION: Black and Asian women had significantly higher papilloma percentages compared to white patients in our single institution review. This institution also showed a statistically significant trend of increasing percentage papillomas from 2012 to 2019. Multi-institutional survey found regional variation in percentage papillomas, ranging from 3% to 9%.

Specialization of a mobile, apex predator affects trophic coupling among adjacent habitats.

Mobile, apex predators are commonly assumed to stabilize food webs through trophic coupling across spatially distinct habitats. The assumption that trophic coupling is common remains largely untested, despite evidence that individual behaviors might limit trophic coupling. We used stable isotope data from common bottlenose dolphins across the Gulf of Mexico to determine if these apex predators coupled estuarine and adjacent, nearshore marine habitats. δ13C values differed among the sites, likely driven by environmental factors that varied at each site, such as freshwater input and seagrass cover. Within most sites, δ13C values differed such that dolphins sampled in the upper reaches of embayments had values indicative of estuarine habitats while those sampled outside or in lower reaches of embayments had values indicative of marine habitats. δ15N values were more similar among and within sites than δ13C values. Data from multiple tissues within individuals corroborated that most dolphins consistently used a narrow range of habitats but fed at similar trophic levels in estuarine and marine habitats. Because these dolphins exhibited individual habitat specialization, they likely do not contribute to trophic coupling between estuarine and adjacent marine habitats at a regional scale, suggesting that not all mobile, apex predators trophically couple adjacent habitats.

Whole-Genome Sequencing for Tracing the Genetic Diversity of Brucella abortus and Brucella melitensis Isolated from Livestock in Egypt.

Brucellosis is a highly contagious zoonosis that occurs worldwide. Whole-genome sequencing (WGS) has become a widely accepted molecular typing method for outbreak tracing and genomic epidemiology of brucellosis. Twenty-nine Brucella spp. (eight B. abortus biovar 1 and 21 B. melitensis biovar 3) were isolated from lymph nodes, milk, and fetal abomasal contents of infected cattle, buffaloes, sheep, and goats originating from nine districts in Egypt. The isolates were identified by microbiological methods and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Differentiation and genotyping were confirmed using multiplex PCR. Illumina MiSeq® was used to sequence the 29 Brucella isolates. Using MLST typing, ST11 and ST1 were identified among B. melitensis and B. abortus, respectively. Brucella abortus and B. melitensis isolates were divided into two main clusters (clusters 1 and 2) containing two and nine distinct genotypes by core-genome SNP analysis, respectively. The genotypes were irregularly distributed over time and space in the study area. Both Egyptian B. abortus and B. melitensis isolates proved to be genomically unique upon comparison with publicly available sequencing from strains of neighboring Mediterranean, African, and Asian countries. The antimicrobial resistance mechanism caused by mutations in rpoB, gyrA, and gyrB genes associated with rifampicin and ciprofloxacin resistance were identified. To the best of our knowledge, this is the first study investigating the epidemiology of Brucella isolates from livestock belonging to different localities in Egypt based on whole genome analysis.

Pulmonary Vein Thrombosis in COVID-19.

Research on COVID-19, the cause of a rapidly worsening pandemic, has led to the observation of laboratory derangements such as a propensity towards a hypercoagulable state. However, there are currently no reports on the incidence of pulmonary venous thrombosis in the setting of COVID-19. We report a case in which follow-up chest CT scans revealed an expansile filling defect in a branch of the right inferior pulmonary vein, which is consistent with pulmonary venous thrombosis. Our objective was to provide insight into an uncommon sequela of COVID-19 and consequently garner increased clinical suspicion for pulmonary VTE during hospitalization.

Molecular Typing of Burkholderia mallei Isolates from Equids with Glanders, India.

We collected 10 Burkholderia mallei isolates from equids in 9 districts in India during glanders outbreaks in 2013-2016. Multilocus variable-number tandem-repeat analysis showed 7 outbreak area-related genotypes. The study highlights the utility of this analysis for epidemiologically tracing of specific B. mallei isolates during outbreaks.

A Whole-Genome-Based Gene-by-Gene Typing System for Standardized High-Resolution Strain Typing of Bacillus anthracis.

Whole-genome sequencing (WGS) has been established for bacterial subtyping and is regularly used to study pathogen transmission, to investigate outbreaks, and to perform routine surveillance. Core-genome multilocus sequence typing (cgMLST) is a bacterial subtyping method that uses WGS data to provide a high-resolution strain characterization. This study aimed at developing a novel cgMLST scheme for Bacillus anthracis, a notorious pathogen that causes anthrax in livestock and humans worldwide. The scheme comprises 3,803 genes that were conserved in 57 B. anthracis genomes spanning the whole phylogeny. The scheme has been evaluated and applied to 584 genomes from 50 countries. On average, 99.5% of the cgMLST targets were detected. The cgMLST results confirmed the classical canonical single-nucleotide-polymorphism (SNP) grouping of B. anthracis into major clades and subclades. Genetic distances calculated based on cgMLST were comparable to distances from whole-genome-based SNP analysis with similar phylogenetic topology and comparable discriminatory power. Additionally, the application of the cgMLST scheme to anthrax outbreaks from Germany and Italy led to a definition of a cutoff threshold of five allele differences to trace epidemiologically linked strains for cluster typing and transmission analysis. Finally, the association of two clusters of B. anthracis with human cases of injectional anthrax in four European countries was confirmed using cgMLST. In summary, this study presents a novel cgMLST scheme that provides high-resolution strain genotyping for B. anthracis. This scheme can be used in parallel with SNP typing methods to facilitate rapid and harmonized interlaboratory comparisons, essential for global surveillance and outbreak analysis. The scheme is publicly available for application by users, including those with little bioinformatics knowledge.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

OBJECTIVE: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.