Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously ...unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria in African children.
We used paediatric safety data from a multi-site, multi-country clinical study conducted in seven African countries (Burkina Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique). Each site compared three out of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) or chlorproguanil/dapsone and artesunate (CD+A). We examine two pharmacovigilance signal detection methods, namely proportional reporting ratio and Bayesian Confidence Propagation Neural Network on the clinical safety dataset.
Among the 4,116 children (6-59 months old) enrolled and followed up for 28 days post treatment, a total of 6,238 adverse events were reported resulting into 346 drug-event combinations. Nine signals were generated both by proportional reporting ratio and Bayesian Confidence Propagation Neural Network. A review of the manufacturer package leaflets, an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD) and further by therapeutic area experts reduced the number of signals to five. The ranking of some drug-adverse reaction pairs on the basis of their signal index differed between the two methods.
Our two data mining methods were equally able to generate suspected signals using the pooled safety data from a phase IIIb/IV clinical trial. This analysis demonstrated the possibility of utilising clinical studies safety data for key pharmacovigilance activities like signal detection and evaluation. This approach can be applied to complement the spontaneous reporting systems which are limited by under reporting.
Paragangliome der A. carotis Erhart, Philipp; Körfer, Daniel; Hoffmann-Wieker, Carola ...
Gefässchirurgie,
11/2022, Volume:
27, Issue:
7
Journal Article
Peer reviewed
Open access
Zusammenfassung
Paragangliome im Kopf-Hals-Bereich sind seltene Tumoren und treten sowohl sporadisch als auch hereditär auf. Sie können Systemerkrankungen darstellen und sollten interdisziplinär ...abgeklärt werden. Nach internistischen, radiologischen und genetischen Gesichtspunkten lassen sich Niedrig-/und Hochrisikopatienten identifizieren. Klinische Herausforderungen sind eine mögliche Metastasierung, multilokuläre Manifestationen und Rezidive. Hereditäre Paragangliome können im Rahmen einer Disposition zusammen mit weiteren Tumorerkrankungen auftreten. Der vorliegende Artikel soll relevante Aspekte zu Paragangliomen der A. carotis zusammenfassen und einen praktikablen Algorithmus zu Diagnostik, Therapie und Nachsorge liefern.
Colletes hederae Schmidt & Westrich, 1993 is a cryptic bee species from the C. succinctus species-group. The previous occurrence and spreading of this species were predominantly in south-western ...Europe. To determine if the species was spreading in Slovak territory, Hedera helix was monitored from autumn 2015. The ivy-bee was first recorded in Slovakia during autumn 2017. This species is widespread inside and around Bratislava; however, it was not recorded under this study in any sites located eastwards. In the Czech Republic, it was not recorded in the south-east part of the country in 2017–2019. In 2020, the occurrence of this species was confirmed in many localities in the south of the country and strong populations were discovered, especially in the towns Znojmo and Mikulov. The populations likely originated from neighbouring Austria, where this species was discovered in 2006 and the localities are usually less than 100 km away from Czech and Slovak localities. A further survey could map a route of the northwards spread of this species.
Molecular epidemiological data on Group A
(GAS) infection in Africa is scarce. We characterized the
types and
-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and ...2018. To reduce the potential for strain mistyping, we used a newly published primer for
-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.
To present a new approach for estimating the "true prevalence" of malaria and apply it to datasets from Peru, Vietnam, and Cambodia.
Bayesian models were developed for estimating both the malaria ...prevalence using different diagnostic tests (microscopy, PCR & ELISA), without the need of a gold standard, and the tests' characteristics. Several sources of information, i.e. data, expert opinions and other sources of knowledge can be integrated into the model. This approach resulting in an optimal and harmonized estimate of malaria infection prevalence, with no conflict between the different sources of information, was tested on data from Peru, Vietnam and Cambodia.
Malaria sero-prevalence was relatively low in all sites, with ELISA showing the highest estimates. The sensitivity of microscopy and ELISA were statistically lower in Vietnam than in the other sites. Similarly, the specificities of microscopy, ELISA and PCR were significantly lower in Vietnam than in the other sites. In Vietnam and Peru, microscopy was closer to the "true" estimate than the other 2 tests while as expected ELISA, with its lower specificity, usually overestimated the prevalence.
Bayesian methods are useful for analyzing prevalence results when no gold standard diagnostic test is available. Though some results are expected, e.g. PCR more sensitive than microscopy, a standardized and context-independent quantification of the diagnostic tests' characteristics (sensitivity and specificity) and the underlying malaria prevalence may be useful for comparing different sites. Indeed, the use of a single diagnostic technique could strongly bias the prevalence estimation. This limitation can be circumvented by using a Bayesian framework taking into account the imperfect characteristics of the currently available diagnostic tests. As discussed in the paper, this approach may further support global malaria burden estimation initiatives.
Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to ...identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10
), rs5104 in APOA4 (P = 1.79 × 10
) and rs4241819 in KLKB1 (P = 5.6 × 10
). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10
). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10
). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.
: Coccidioidomycosis or Valley Fever is a fungal disease that occurs primarily in the southwestern United States. Of the estimated 150,000 U. S. coccidioidomycosis infections per year, approximately ...60% occur in Arizona, making this state the focal point for investigation of the disease. In this manuscript, we describe the epidemiology of coccidioidomycosis reported in Arizona over the last decade, hypotheses for the findings, and Arizona's response to the rising epidemic. Coccidioidomycosis surveillance data in Arizona consist of basic demographics of all laboratory and physician‐diagnosed cases, the reporting of which has been mandated by law since 1997. The rate of reported coccidioidomycosis has more than quadrupled over the last decade from 21 cases per 100,000 population in 1997 to 91 cases per 100,000 in 2006 (P < 0.001). Case rates in older age groups (≥65 years old) have more than doubled since 2000 (P < 0.001). These data demonstrate the rising coccidioidomycosis epidemic in Arizona, especially among the elderly. The increase in the numbers of reported cases can be partially explained by the institution of mandatory laboratory reporting in 1997, but the cause of the persistent rise after 1999 is unknown. Further investigation of coccidioidomycosis will not only assist with the development of public health interventions to control this disease in Arizona and the southwestern United States, but will also provide important information to prepare for a bioterrorism event caused by this select agent.
A considerable share of greenhouse gas emissions, especially N₂O, is caused by agriculture, part of which can be attributed to indirect soil emissions via leaching and runoff. Countries have to ...report their annual emissions, which are usually calculated by using the default value of 0.3 for FracLEACH, a factor that represents the fraction of nitrogen losses compared to total nitrogen inputs and sources. In our study we used 22 lysimeters, covering a wide range of soils, climatic conditions and management practices in Austria, to evaluate nitrogen losses through leaching and to calculate FracLEACH. The terms of the nitrogen mass balance of the lysimeters were directly measured for several years. Both grassland and arable land plots gave significantly smaller values of FracLEACHthan the default value. For grassland, FracLEACHvalues of only 0.02 were found which varied very little over the entire observation period. For arable sites, FracLEACHvalues were higher (around 0.25) and showed significant variability between years due to variations in crop rotation, fertilization rates, and yields.
Schmidt & Westrich, 1993 is a cryptic bee species from the
species-group. The previous occurrence and spreading of this species were predominantly in south-western Europe. To determine if the species ...was spreading in Slovak territory,
was monitored from autumn 2015. The ivy-bee was first recorded in Slovakia during autumn 2017. This species is widespread inside and around Bratislava; however, it was not recorded under this study in any sites located eastwards. In the Czech Republic, it was not recorded in the south-east part of the country in 2017-2019. In 2020, the occurrence of this species was confirmed in many localities in the south of the country and strong populations were discovered, especially in the towns Znojmo and Mikulov. The populations likely originated from neighbouring Austria, where this species was discovered in 2006 and the localities are usually less than 100 km away from Czech and Slovak localities. A further survey could map a route of the northwards spread of this species.
Background
The
B
inational
B
order
I
nfectious
D
isease
S
urveillance program began surveillance for severe acute respiratory infections (
SARI
) on the
US
–Mexico border in 2009. Here, we describe ...patients in
S
outhern
A
rizona.
Methods
Patients admitted to five acute care hospitals that met the
SARI
case definition (temperature ≥37·8°C or reported fever or chills with history of cough, sore throat, or shortness of breath in a hospitalized person) were enrolled. Staff completed a standard form and collected a nasopharyngeal swab which was tested for selected respiratory viruses by reverse transcription polymerase chain reaction.
Results
From October 2010–September 2014, we enrolled 332
SARI
patients. Fifty‐two percent were male and 48% were white non‐Hispanic. The median age was 63 years (47% ≥65 years and 5·2% <5 years). During hospitalization, 51 of 230 (22%) patients required intubation, 120 of 297 (40%) were admitted to intensive care unit, and 28 of 278 (10%) died. Influenza vaccination was 56%. Of 309 cases tested, 49 (16%) were positive for influenza viruses, 25 (8·1%) for human metapneumovirus, 20 (6·5%) for parainfluenza viruses, 16 (5·2%) for coronavirus, 11 (3·6%) for respiratory syncytial virus, 10 (3·2%) for rhinovirus, 4 (1·3%) for rhinovirus/enterovirus, 3 (1·0%) for enteroviruses, and 3 (1·0%) for adenovirus. Among the 49 influenza‐positive specimens, 76% were influenza A (19 H3N2, 17 H1N1pdm09, and 1 not subtyped), and 24% were influenza B.
Conclusion
Influenza viruses were a frequent cause of
SARI
in hospitalized patients in Southern Arizona. Monitoring respiratory illness in border populations will help better understand the etiologies. Improving influenza vaccination coverage may help prevent some
SARI
cases.
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