Introduction
Adverse drug reactions related to drug–drug interactions cause harm to patients. There is a body of research on signal detection for drug interactions in collections of individual case ...reports, but limited use in regular pharmacovigilance.
Objective
The aim of this study was to evaluate the feasibility of signal detection of drug–drug interactions in collections of individual case reports of suspected adverse drug reactions.
Methods
This study was conducted in VigiBase, the WHO global database of individual case safety reports. The data lock point was 31 August 2016, which provided 13.6 million reports for analysis after deduplication. Statistical signal detection was performed using a previously developed predictive model for possible drug interactions. The model accounts for an interaction disproportionality measure, expressed suspicion of an interaction by the reporter, potential for interaction through cytochrome P450 activity of drugs, and reported information indicative of unexpected therapeutic response or altered therapeutic effect. Triage filters focused the preliminary signal assessment on combinations relating to serious adverse events with case series of no more than 30 reports from at least two countries, with at least one report during the previous 2 years. Additional filters sought to eliminate already known drug interactions through text mining of standard literature sources. Preliminary signal assessment was performed by a multidisciplinary group of pharmacovigilance professionals from Uppsala Monitoring Centre and collaborating organizations, whereas in-depth signal assessment was performed by experienced pharmacovigilance assessors.
Results
We performed preliminary signal assessment for 407 unique drug pairs. Of these, 157 drug pairs were considered already known to interact, whereas 232 were closed after preliminary assessment for other reasons. Ten drug pairs were subjected to in-depth signal assessment and an additional eight were decided to be kept under review awaiting additional reports. The triage filters had a major impact in focusing our preliminary signal assessment on just 14% of the statistical signals generated by the predictive model for drug interactions. In-depth assessment led to three signals communicated with the broader pharmacovigilance community, six closed signals and one to be kept under review.
Conclusion
This study shows that signals of adverse drug interactions can be detected through broad statistical screening of individual case reports. It further shows that signal assessment related to possible drug interactions requires more detailed information on the temporal relationship between different drugs and the adverse event. Future research may consider whether interaction signal detection should be performed not for individual adverse event terms but for pairs of drugs across a spectrum of adverse events.
Acetic acid bacteria (AAB) are microorganisms widely distributed in nature. Although this group is involved in the spoilage of some foods, AAB are of great industrial interest, and their ...functionality is still poorly understood. AAB convert ethanol, sugars and polyols into various organic acids, aldehydes and ketones
oxidative fermentation. These metabolites are produced during a succession of biochemical reactions in various fermented foods and beverages, such as vinegar, kombucha, water kefir, lambic and cocoa. Furthermore, important products such as gluconic acid and ascorbic acid precursors can be produced industrially from their metabolism. The development of new AAB-fermented fruit drinks with healthy and functional properties is an interesting niche for research and the food industry to explore, as it can meet the needs of a wide range of consumers. Exopolysaccharides such as levan and bacterial cellulose have unique properties, but they need to be produced on a larger scale to expand their applications in this area. This work emphasizes the importance and applications of AAB during the fermentation of various foods, their role in the development of new beverages as well as numerous applications of levan and bacterial cellulose.
The aim of this study was to isolate
Aspergillus
section
Nigri
from onion samples bought in supermarkets and to analyze the fungal isolates by means of molecular data in order to differentiate
A
.
...niger
and
A
.
welwitschiae
species from the other non-toxigenic species of black aspergilli, and detect genes involved in the biosynthesis of ochratoxin A and fumonisin B
2
.
Aspergillus
section
Nigri
were found in 98% (94/96) of the onion samples. Based on the results of multiplex PCR (performed on 500 randomly selected strains), 97.4% of the
Aspergillus
section
Nigri
strains were recognized as
A
.
niger/A
.
welwitschiae
. Around half of them were subjected to partial sequencing of the
CaM
gene to distinguish one from the other. A total of 97.9% of the isolates were identified as
A
.
welwitschiae
and only 2.1% as
A
.
niger
. The
fum8
gene, involved in fumonisin B
2
biosynthesis, was found in 36% of
A
.
welwitschiae
isolates, but
radH
and
pks
genes, involved in ochratoxin A biosynthesis, were found in only 2.8%. The presence/absence of
fum8
gene in the
A
.
welwitschiae
genome is closely associated with ability/inability of the isolates to produce fumonisin in vitro. Based on these results, we suggest that in-depth studies are conducted to investigate the presence of fumonisins in onion bulbs.
The garlic contains sulfur bioactive compounds responsible for medicinal properties. The decrease of these compounds due to inadequate storage conditions reduces the beneficial properties and favors ...infection by microorganisms. Several studies have shown high frequency of garlic infected with
Aspergillus
section
Nigri
that potentially produce mycotoxin. Garlic samples were collected in markets of Brazil and a total of 32 samples (of 36) had the fungal infection with predominant genus
Aspergillus
(50.3%),
Penicillium
(34.7%), and
Fusarium
(11%). A total of 63% (649/1031) of infection with
Aspergillus
section
Nigri
, of which 60 isolates were selected for analysis of genetic variability that resulted in 4 clusters. Representatives of clusters were identified by the calmodulin gene. Isolates from cluster I were subdivided into A-I and identified as
A. niger
(16 isolates) and the isolates of clusters B-I, II, and III were identified as
A. welwitschiae
(43 isolates). Besides, an isolate of the IV-cluster was identified by
A. luchuensis
. Further, we used the multiplex PCR to verify genotypes of 59 isolates, and none of these had OTA production-associated genotype. Moreover, 19
A. welwitschiae
and 15
A. niger
were FB
2
production-associated genotype. Our study is the first report to the incidence of garlic infection in Brazil and to show that
A. welwitschiae
causes most of these infections.
The subject of this review is to discuss some aspects related to the use of biopolymeric matrices as carriers for plant-growth promoting bacteria (PGPB) in agricultural systems as a possible ...technological solution for the establishment of agricultural production practices that result in fewer adverse impacts on the environment, reporting some promising and interesting results on the topic. Results from the encapsulation of different PGPB on alginate, starch, chitosan, and gelatin matrices are discussed, systematizing some advances made in this area of knowledge in recent years. Encapsulation of these bacteria has been shown to be an effective method for protecting them from unsuitable environments, and these new products that can act as biofertilizers and biopesticides play an important role in the establishment of a sustainable and modern agriculture. These new products are technological solutions for replacing deleterious chemical fertilizers and pesticides, maintaining soil fertility and stability, and improving crop productivity and food security. Finally, in the near future, scale-up studies will have to provide new information about the large-scale production of these materials as well as their application in the field under different biotic and abiotic stress conditions.
The completeness of adverse event (AE) reports, crucial for assessing putative causal relationships, is measured using the vigiGrade completeness score in VigiBase, the World Health Organization ...global database of reported potential AEs. Malaysian reports have surpassed the global average score (approximately 0.44), achieving a 5-year average of 0.79 (SD 0.23) as of 2019 and approaching the benchmark for well-documented reports (0.80). However, the contributing factors to this relatively high report completeness score remain unexplored.
This study aims to explore the main drivers influencing the completeness of Malaysian AE reports in VigiBase over a 15-year period using vigiGrade. A secondary objective was to understand the strategic measures taken by the Malaysian authorities leading to enhanced report completeness across different time frames.
We analyzed 132,738 Malaysian reports (2005-2019) recorded in VigiBase up to February 2021 split into historical International Drug Information System (INTDIS; n=63,943, 48.17% in 2005-2016) and newer E2B (n=68,795, 51.83% in 2015-2019) format subsets. For machine learning analyses, we performed a 2-stage feature selection followed by a random forest classifier to identify the top features predicting well-documented reports. We subsequently applied tree Shapley additive explanations to examine the magnitude, prevalence, and direction of feature effects. In addition, we conducted time-series analyses to evaluate chronological trends and potential influences of key interventions on reporting quality.
Among the analyzed reports, 42.84% (56,877/132,738) were well documented, with an increase of 65.37% (53,929/82,497) since 2015. Over two-thirds (46,186/68,795, 67.14%) of the Malaysian E2B reports were well documented compared to INTDIS reports at 16.72% (10,691/63,943). For INTDIS reports, higher pharmacovigilance center staffing was the primary feature positively associated with being well documented. In recent E2B reports, the top positive features included reaction abated upon drug dechallenge, reaction onset or drug use duration of <1 week, dosing interval of <1 day, reports from public specialist hospitals, reports by pharmacists, and reaction duration between 1 and 6 days. In contrast, reports from product registration holders and other health care professionals and reactions involving product substitution issues negatively affected the quality of E2B reports. Multifaceted strategies and interventions comprising policy changes, continuity of education, and human resource development laid the groundwork for AE reporting in Malaysia, whereas advancements in technological infrastructure, pharmacovigilance databases, and reporting tools concurred with increases in both the quantity and quality of AE reports.
Through interpretable machine learning and time-series analyses, this study identified key features that positively or negatively influence the completeness of Malaysian AE reports and unveiled how Malaysia has developed its pharmacovigilance capacity via multifaceted strategies and interventions. These findings will guide future work in enhancing pharmacovigilance and public health.
A novel fungal species, Aspergillus labruscus sp. nov., has been found in Brazil during an investigation of the fungal species present on the surface of grape berries (Vitis labrusca L.) for use in ...the production of concentrated grape juice. It seems to be associated to V. labrusca, and has never been recovered from Vitis vinifera. This new species belonging to Aspergillus subgenus Circumdati section Nigri is described here using morphological characters, extrolite profiling, partial sequence data from the BenA and CaM genes, and internal transcribed spacer sequences of ribosomal DNA. Phenotypic and molecular data enabled this novel species to be clearly distinguished from other black aspergilli. A. labruscus sp. nov. is uniseriate, has yellow mycelium, poor sporulation on CYA at 25 °C, abundant salmon to pink sclerotia and rough conidia. Neoxaline and secalonic acid D were consistently produced by isolates in this taxon. The type strain of A. labruscus sp. nov. is CCT 7800 (T) = ITAL 22.223 (T) = IBT 33586 (T).
Abstract
Background
Signals of adverse drug reactions (ADRs) form the basis of some regulatory risk-minimization actions in pharmacovigilance. Reviews of limited scope have highlighted that such ...signals are mostly supported by reports of ADRs or multiple types of evidence. The time that elapses between a report of a suspected ADR and the communication of a signal has not been systematically characterized. Neither has the features of reports of suspected ADRs that authors used to support putative causal relationships, although difficulties with establishing causal relationships between medicinal products and adverse events have been highlighted. The objectives of this study will be to describe the evidence underpinning signals in pharmacovigilance, the features of reports of ADRs supporting signals, and the time that it takes to communicate a signal.
Methods
We shall retrieve records from PubMed, EMBASE, Web of Science, and PsycINFO (from inception onwards), without language/design restrictions, and apply backward citation screening. We shall hand-search the websites of 35 regulatory agencies/authorities, restricted publications from the Uppsala Monitoring Centre, and drug bulletins. Signals will be requested from the competent stakeholder, if absent from websites. We shall use VigiBase, the World Health Organization’s Global Individual Case Safety Report database, to determine the dates on which ADRs were reported. We shall manage records using EndNote (v. 8.2); one reviewer will screen titles/abstracts and full texts, a second will cross-validate the findings, and a third will arbitrate disagreements. Data will be charted via the Systematic Reviews Data Repository, following the same procedures as for data retrieval. Evidence will be categorized according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Features of reports of ADRs will be coded. Tables will display frequencies of types of evidence and features of reports of ADRs. We shall use plots or pictograms (if appropriate) to represent the time from the first report of a suspected ADR to a signal.
Discussion
We expect the findings from this review will allow a better understanding of global patterns of similarities or differences in terms of supporting evidence and timing of communications and identify relevant research questions for future systematic reviews.
Systematic review registration
osf.io/a4xns
Some species from Aspergillus section Nigri are morphologically very similar and altogether have been called A. niger aggregate. Although the species included in this group are morphologically very ...similar, they differ in their ability to produce mycotoxins and other metabolites and their taxonomical status has evolved continuously. Among them, A. niger and A. welwitschiae are ochratoxin A and fumonisin B2 producers and their detection and/or identification is of crucial importance for food safety. The aim of this study was the development of a real-time PCR-based method for simultaneous discrimination of A. niger and A. welwitschiae from other species of the A. niger aggregate isolated from coffee beans. One primer pair and a hybridization probe specific for detection of A. niger and A. welwitschiae strains were designed based on the BenA gene sequences, and used in a Real-time PCR assay for the rapid discrimination between both these species from all others of the A. niger aggregate. The Real-time PCR assay was shown to be 100% efficient in discriminating the 73 isolates of A. niger/A. welwitschiae from the other A. niger aggregate species analyzed as a negative control. This result testifies to the use of this technique as a good tool in the rapid detection of these important toxigenic species.
•A real-time PCR assay for A. niger/A. welwitschiae detection was proposed.•A. niger was the most common Aspergillus niger aggregate in coffee beans.•A. welwitschiae, A. luchuensis, A. neoniger and A. tubingensis were also found.
Background: Rhinomanometry, acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) are popular methods for nasal patency evaluation. The aim of the present study was to compare these three ...methods with the reported nasal symptoms to determine the best diagnostic tool to assess nasal obstruction. Methods: 101 subjects were evaluated using PNIF, 4-phase rhinomanometry (4PR), AR, Visual Analogue Scale for nasal obstruction (VAS-NO) and Sino-Nasal Outcome Test (SNOT-22). Correlations among PNIF, 4PR, AR, VAS-NO and SNOT-22 were obtained. Results: VAS-NO and SNOT-22 were moderately correlated with each other (r = 0.54, p < 0.001). 4PR was moderately correlated with PNIF (r = −0.31, p = 0.0016) and AR (r = −0.5, p < 0.001). VAS-NO was mildly correlated with PNIF (r = −0.29, p = 0.0034). SNOT-22 was moderately correlated with PNIF (r = −0.31, p = 0.0017). After dividing the population into symptomatic and asymptomatic subjects, based on their VAS-NO score, the former showed significantly lower PNIF values (p = 0.009) and higher 4PR values (p = 0.013) compared to the latter ones. Conclusion: PNIF and 4PR showed a significant moderate correlation with each other, but PNIF showed a significant correlation (weak-moderate) with the reported nasal symptom scores.
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