Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register

Objectives

Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim of this study was to develop an application to identify instances of Adverse Drug Events (ADEs) from free text psychiatric EHRs.

Methods

We used the GATE Natural Language Processing (NLP) software to mine instances of ADEs from free text content within the Clinical Record Interactive Search (CRIS) system, a de-identified psychiatric case register developed at the South London and Maudsley NHS Foundation Trust, UK. The tool was built around a set of four movement disorders (extrapyramidal side effects [EPSEs]) related to antipsychotic therapy and rules were then generalised such that the tool could be applied to additional ADEs. We report the frequencies of recorded EPSEs in patients diagnosed with a Severe Mental Illness (SMI) and then report performance in identifying eight other unrelated ADEs.

Results

The tool identified EPSEs with >0.85 precision and >0.86 recall during testing. Akathisia was found to be the most prevalent EPSE overall and occurred in the Asian ethnic group with a frequency of 8.13%. The tool performed well when applied to most of the non-EPSEs but least well when applied to rare conditions such as myocarditis, a condition that appears frequently in the text as a side effect warning to patients.

Conclusions

The developed tool allows us to accurately identify instances of a potential ADE from psychiatric EHRs. As such, we were able to study the prevalence of ADEs within subgroups of patients stratified by SMI diagnosis, gender, age and ethnicity. In addition we demonstrated the generalisability of the application to other ADE types by producing a high precision rate on a non-EPSE related set of ADE containing documents.

Availability

The application can be found at http://git.brc.iop.kcl.ac.uk/rmallah/dystoniaml.     

Severity of Depression,Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort

Background

Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association.

Methods

We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases.

Findings

Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD.

Conclusion

This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress.     

In situ measurements of bioluminescence response of Gonyaulax spinifera to various mechanical stimuli

A conspicuous bioluminescence during nighttime was reported in an aquaculture farm in the Cochin estuary due to Gonyaulax spinifera bloom on March 20, 2020. In situ measurements on bioluminescence was carried out during nighttime to quantify the response of G. spinifera to various mechanical stimuli. The bioluminescence intensity (BI) was measured using Glowtracka, an advanced single channel sensor, attached to a Conductivity–Temperature–Depth Profiler. In steady environment, without any external stimuli, the bioluminescence generated due to the movement of fishes and shrimps in the water column was not detected by the sensor. However, stimuli such as a hand splash, oar and swimming movements, and a mixer could generate measurable bioluminescence responses. An abundance of?~?2.7?×?10⁶ cells L^?1 of G. spinifera with exceptionally high chlorophyll a of 25 mg m^?3 was recorded. The BI in response to hand splash was recorded as high as 1.6?×?10¹¹ photons cm^?2 s^?1. Similarly, BI of?~?1–6?×?10¹⁰ photons cm^?2 s^?1 with a cumulative bioluminescence of?~?2.51?×?10¹² photons cm^?2 (for 35 s) was recorded when there is a mixer with a constant force of 494 N/800 rpm min^?1. The response of G. spinifera was spontaneous with no time lapse between application of stimuli and the bioluminescence response. Interestingly, in natural environment, application of stimulus for longer time periods (10 min) does not lower the bioluminescence intensity due to the replenishment of water thrusted in by the mixer from surrounding areas. We also demonstrated that the bioluminescence intensity decreases with increase in distance from the source of stimuli (mixer) (av. 1.84?×?10¹⁰ photons cm^?2 s^?1 at 0.2 m to av. 0.05?×?10¹⁰ photons cm^?2 s^?1 at 1 m). The BI was highest in the periphery of the turbulent wake generated by the stimuli (av. 3.1?×?10¹⁰ photons cm^?2 s^?1) compared to the center (av. 1.8?×?10¹⁰ photons cm^?2 s^?1). When the stimuli was applied vertically down, the BI decreased from 0.2 m (0.3?×?10¹⁰ photons cm^?2 s^?1) to 0.5 m (0.10?×?10¹⁰ photons cm^?2 s^?1). Our study demonstrates that the BI of G. spinifera increases with increase in mechanical stimuli and decreases with increase in distance from the stimuli.

     

Comparative role of animal manure and vegetable waste induced compost for polluted soil restoration and maize growth

Soil amendment with two types of composts: animal manure (AC) and vegetable waste (VC) induced composts have potential to alleviate Cd toxicity to maize in contaminated soil. Therefore, Cd mobility in waste water irrigated soil can be addressed through eco-friendly and cost effective organic soil amendments AC and VC that eventually reduces its translocation from polluted soil to maize plant tissues. The comparative effectiveness of AC and VC at 3% rate were evaluated on Cd solubility, its accumulation in maize tissues, translocation from root to shoot, chlorophyll contents, plant biomass, yield and soil properties (pH, NPK, OM). Results revealed that the addition of organic soil amendments significantly minimized Cd mobility and leachability in soil by 58.6% and 47%, respectively in VC-amended soil over control. While, the reduction was observed by 61.7% and 57%, respectively when AC was added at 3% over control. Comparing the control soil, Cd uptake effectively reduced via plants shoots and roots by 50%, 46% respectively when VC was added in polluted soil. However, Cd uptake was decreased in maize shoot and roots by 58% and 52.4% in AC amended soil at 3% rate, respectively. Additionally, NPK contents were significantly improved in polluted soil as well as in plant tissues in both composts amended soil Comparative to control, the addition of composts significantly improved the maize dry biomass and chlorophyll contents at 3% rate. Thus, present study confirmed that the addition of animal manure derived compost (AC) at 3% rate performed well and might be consider the suitable approach relative to vegetable compost for maize growth in polluted soil.     

Biological control of strawberry crown rot,root rot and grey mould by the beneficial fungus Aureobasidium pullulans

Utilization of biocontrol agents is a sustainable approach to reduce plant diseases caused by fungal pathogens. In the present study, we tested the effect of the candidate biocontrol fungus Aureobasidium pullulans (De Bary) G. Armaud on strawberry under in vitro and in vivo conditions to control crown rot, root rot and grey mould caused by Phytophthora cactorum (Lebert and Cohn) and Botrytis cinerea Pers, respectively. A dual plate confrontation assay showed that mycelial growth of P. cactorum and B. cinerea was reduced by 33–48% when challenged by A. pullulans as compared with control treatments. Likewise, detached leaf and fruit assays showed that A. pullulans significantly reduced necrotic lesion size on leaves and disease severity on fruits caused by P. cactorum and B. cinerea. In addition, greenhouse experiments with whole plants revealed enhanced biocontrol efficacy against root rot and grey mould when treated with A. pullulans either in combination with the pathogen or pre-treated with A. pullulans followed by inoculation of the pathogens. Our results demonstrate that A. pullulans is an effective biocontrol agent to control strawberry diseases caused by fungal pathogens and can be an effective alternative to chemical-based fungicides.

     

Flacourtia indica fruit extract modulated antioxidant gene expression,prevented oxidative stress and ameliorated kidney dysfunction in isoprenaline administered rats

This study evaluated the effect of Flacourtia indica fruit extract against isoprenaline (ISO) induced renal damage in rats. This investigation showed that ISO administration in rats increased the level oxidative stress biomarkers such as malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation product (APOP) in kidneys followed by a decrease in antioxidant enzymes functions. Flacourtia indica fruit extract, which is rich in strong antioxidants, also reduced the MDA, NO and APOP level in kidney of ISO administered rats. Inflammation and necrosis was also visible in kidney section of ISO administered rats which was significantly prevented by atenolol and Flacourtia indica fruit extract. Moreover, atenolol and Flacourtia indica fruit extract also modulated the genes expressions related to inflammation and oxidative stress in kidneys. The beneficial effects could be attributed to the presence of a number of phenolic antioxidants. This study suggests that Flacourtia indica fruit extract may prevent kidney dysfunction in ISO administered rats, probably by preventing oxidative stress and inflammation.     

Drought induced programmed cell death and associated changes in antioxidants, proteases, and lipid peroxidation in wheat leaves

Two wheat (Triticum aestivum L.) genotypes with varying degree of drought tolerance were used to analyze programmed cell death (PCD) and related biochemical changes under drought stress. Drought induced PCD in leaves, as evident by internucleosomal nDNA fragmentation, was observed in sensitive genotype Nesser. Drought tolerant genotype (FD-83) showed higher peroxidase, superoxide dismutase, and catalase activities and ascorbate content under drought stress compared to sensitive genotype. Total phenolic content increased whereas lipid peroxidation remained un-changed under drought in FD-83. In contrast, drought enhanced the proteases and ascorbate peroxidase activities and lipid peroxidation (MDA content) in Nesser.     

Inhibition of Protein Synthesis Alters Protein Degradation through Activation of Protein Kinase B (AKT)

The homeostasis of protein metabolism is maintained and regulated by the rates of protein biosynthesis and degradation in living systems. Alterations of protein degradation may regulate protein biosynthesis through a feedback mechanism. Whether a change in protein biosynthesis modulates protein degradation has not been reported. In this study, we found that inhibition of protein biosynthesis induced phosphorylation/activation of AKT and led to phosphorylation of AKT target substrates, including FoxO1, GSK3α/β, p70S6K, AS160, and the E3 ubiquitin ligase MDM2. Phosphorylation of ribosomal protein S6 was also modulated by inhibition of protein biosynthesis. The AKT phosphorylation/activation was mediated mainly through the PI3K pathway because it was blocked by the PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002. The activated AKT phosphorylated MDM2 at Ser¹⁶⁶ and promoted degradation of the tumor suppressor p53. These findings suggest that inhibition of protein biosynthesis can alter degradation of some proteins through activation of AKT. This study reveals a novel regulation of protein degradation and calls for caution in blocking protein biosynthesis to study the half-life of proteins.     

Synthesis of 2-methoxybenzoylhydrazone and evaluation of their antileishmanial activity

Compounds 1–25 showed varying degree of antileishmanial activities with IC₅₀ values ranging between 1.95 and 88.56 μM. Compounds 2, 10, and 11 (IC₅₀ = 3.29 ± 0.07 μM, 1.95 ± 0.04 μM, and 2.49 ± 0.03 μM, respectively) were found to be more active than standard pentamidine (IC₅₀ = 5.09 ± 0.04 μM). Compounds 7 (IC₅₀ = 7.64 ± 0.1 μM), 8 (IC₅₀ = 13.17 ± 0.46 μM), 18 (IC₅₀ = 13.15 ± 0.02 μM), and 24 (IC₅₀ = 15.65 ± 0.41 μM) exhibited good activities. Compounds 1, 3, 4, 5, 9, 12, 15, 18, and 19 were found to be moderately active. Compounds 13, 14, 16, 17, 20–25 showed weak activities with IC₅₀ values ranging between 57 and 88 μM.