Morphological and electrophysiological characterization of a novel displaced astrocyte in the mouse retina.

Astrocytes throughout the central nervous system are heterogeneous in both structure and function. This diversity leads to tissue-specific specialization where morphology is adapted to the surrounding neuronal circuitry, as seen in Bergman glia of the cerebellum and Müller glia of the retina. Because morphology can be a differentiating factor for cellular classification, we recently developed a mouse where glial-fibrillary acidic protein (GFAP)-expressing cells stochastically label for full membranous morphology. Here we utilize this tool to investigate whether morphological and electrophysiological features separate types of mouse retinal astrocytes. In this work, we report on a novel glial population found in the inner plexiform layer and ganglion cell layer which expresses the canonical astrocyte markers GFAP, S100ß, connexin-43, Sox2 and Sox9. Apart from their retinal layer localization, these cells are unique in their radial distribution. They are notably absent from the mid-retina but are heavily concentrated near the optic nerve head, and to a lesser degree the peripheral retina. Additionally, their morphology is distinct from both nerve fiber layer astrocytes and Müller glia, appearing more similar to amacrine cells. Despite this structural similarity, these cells lack protein expression of common neuronal markers. Additionally, they do not exhibit action potentials, but rather resemble astrocytes and Müller glia in their small amplitude, graded depolarization to both light onset and offset. Their structure, protein expression, physiology, and intercellular connections suggest that these cells are astrocytic, displaced from their counterparts in the nerve fiber layer. As such, we refer to these cells as displaced retinal astrocytes.

Improving usual care outcomes in major depression in youth by targeting memory specificity: A randomized controlled trial of adjunct computerized memory specificity training (c-MeST).

OBJECTIVE: Extending on previous findings that computerized MeST (c-MeST) improves memory specificity and depressive symptoms in Major Depressive Disorder (MDD) in adults, this study aimed to assess the effects of c-MeST in youth with MDD on memory specificity and depression in addition to other treatment. METHODS: Participants aged 15-25 (N = 359, 76 % female; M age = 19.2, SD = 3.1), receiving predominantly psychological therapy or counseling (85 %) and/or antidepressants (52 %) were randomized to usual care and c-MeST or usual care. Cognitive and clinical outcomes were assessed at baseline and at one, three, and six-month follow-ups. RESULTS: The usual care and c-MeST group reported higher memory specificity at one-month (d = 0.42, p = .022), but not at three or six months (d's < 0.15, p's > 0.05). The rate of MDE was numerically lower in the c-MeST group at each follow-up time-point, but group was not a statistically significant predictor at one month (64 % usual care and c-MeST vs. 68 % usual care, OR = 0.81, p = .606), three months (67 % usual care and c-MeST vs. 72 % usual care, OR = 0.64, p = .327) or six months (55 % usual care and c-MeST vs. 68 % usual care, OR = 0.56, p = .266). The usual care and c-MeST group did report lower depressive symptoms at one month (d = 0.42, p = .023) and six-months (d = 0.84, p = .001), but not three-months (d = 0.13, p > .05). CONCLUSIONS: c-MeST may reduce symptoms in youth with MDD when provided alongside other treatments. However, there are significant limitations to this inference, including high attrition in the study and a need for more data on the acceptability of the intervention.

Water-soluble microencapsulation using gum Arabic and skim milk enhances viability and efficacy of Pediococcus acidilactici probiotic strains for application in broiler chickens.

Objective: This study aimed to develop and evaluate the effectiveness of a water-soluble microencapsulation method for probiotic strains using gum Arabic (GA) and skim milk (SKM) over a three-month storage period following processing. Methods: Four strains of Pediococcus acidilactici (BYF26, BYF20, BF9, and BF14) that were typical lactic acid bacteria (LAB) isolated from the chicken gut were mixed with different ratios of gum Arabic (GA) and skim milk (SKM) as coating agents before spray drying at an inlet temperature 140°C. After processing, the survivability and probiotic qualities of the strains were assessed from two weeks to three months of storage at varied temperatures, and de-encapsulation was performed to confirm the soluble properties. Finally, the antibacterial activity of the probiotics was assessed under simulated gastrointestinal conditions. Results: As shown by scanning electron microscopy, spray-drying produced a spherical, white-yellow powder. The encapsulation efficacy (EE percent) was greatest for a coating containing a combination of 30% gum Arabic: 30% skim milk (w/v) (GA:SKM30) compared to lower concentrations of the two ingredients (p<0.05). Coating with GA:SKM30 (w/v) significantly enhanced (p<0.05) BYF26 survival under simulated gastrointestinal conditions (pH 2.5-3) and maintained higher survival rates compared to non-encapsulated cells under an artificial intestinal juices (AIJ) condition of pH 6. De-encapsulation tests indicated that the encapsulated powder dissolved in water while keeping viable cell counts within the effective range of 106 for 6 hours. In addition, following three months storage at 4°C, microencapsulation of BYF26 in GA:SKM30 maintained both the number of viable cells (p<0.05) and the preparation's antibacterial efficacy against pathogenic bacteria, specifically strains of Salmonella. Conclusion: Our prototype water-soluble probiotic microencapsulation GA:SKM30 effectively maintains LAB characteristics and survival rates, demonstrating its potential for use in preserving probiotic strains that can be used in chickens and potentially in other livestock.

A right to health-based approach to dental caries: towards a comprehensive control strategy.

BACKGROUND: Health is a matter of human rights and dental caries is the most common non-communicable disease (NCD) globally. Consequently, dental caries is a matter of human rights and its control, particularly prevention, must be a priority. Although largely preventable, this is too often neglected, both in the literature of human rights- and health law, and in dental research. The right to oral health has recently been acknowledged by the World Health Organization (WHO), but it is insufficiently clear what this right entails. SUMMARY: This article introduces a right to health-based narrative in the context of dental caries. The right to health is stipulated in human rights treaties, including the International Covenant on Economic, Social and Cultural Rights (ICESCR) and the Convention on the Rights of the Child (CRC). States that are Parties to these treaties, which are virtually all States globally, are mandated to ensure the enjoyment of individuals' right to the highest attainable standard of health, including oral health. KEY MESSAGES: Dental caries is a matter of human rights. States have binding obligations to address dental caries: they require the regulation of the healthcare system, i.e. the traditional focus on operative care, but also put the regulation of other risk factors on an equal footing, such as the regulation of the living environment and access to fluoride. A right to health-based approach to dental caries thus offers a comprehensive approach to dental caries control, particularly prevention.

Reducing the harms of alcohol: nutritional interventions and functional alcohol alternatives.

The health risks and harm associated with regular alcohol consumption are well documented. In a recent WHO statement published in The Lancet Public Health alcohol consumption has been estimated to contribute worldwide to 3 million deaths in 2016 while also being responsible for 5·1% of the global burden of disease and injury. The total elimination of alcohol consumption, which has been long imbedded in human culture and society, is not practical and prohibition policies have proved historically ineffective. However, valuable strategies to reduce alcohol harms are already available and improved alternative approaches are currently being developed. Here, we will review and discuss recent advances on two main types of approaches, that is nutritional interventions and functional alcohol alternatives.

Sensitivity analysis of paediatric knee kinematics to the graft surgical parameters during anterior cruciate ligament reconstruction: A sequentially linked neuromusculoskeletal-finite element analysis.

BACKGROUND AND OBJECTIVE: Incidence of paediatric anterior cruciate ligament (ACL) rupture has increased substantially over recent decades. Following ACL rupture, ACL reconstruction (ACLR) surgery is typically performed to restore passive knee stability. This surgery involves replacing the failed ACL with a graft, however, surgeons must select from range of surgical parameters (e.g., type, size, insertion, and pre-tension) with no robust evidence guiding these decisions. This study presents a systemmatic computational approach to study effects of surgical parameter variation on kinematics of paediatric knees. METHODS: This study used sequentially-linked neuromusculoskeletal (NMSK) finite element (FE) models of three paediatric knees to estimate the: (i) sensitivity of post-operative knee kinematics to four surgical parameters (type, size, insertion, and pre-tension) through multi-input multi-output sensitivity analysis; (ii) influence of motion and loading conditions throughout stance phase of walking gait on sensitivity indices; and (iii) influence of subject-specific anatomy (i.e., knee size) on sensitivivty indices. A previously validated FE model of the intact knee for each subject served as a reference against which ACLR knee kinematics were compared. RESULTS: Sensitivity analyses revealed significant influences of surgical parameters on ACLR knee kinematics, albeit without discernible trend favouring any one parameter. Graft size and pre-tension were primary drivers of variation in knee translations and rotations, however, their effects fluctuated across stance indicating motion and loading conditions affect system sensitivity to surgical parameters. Importantly, the sensitivity of knee kinematics to surgical parameter varied across subjects, indicating geometry (i.e., knee size) influenced system sensitivity. Notably, alterations in graft parameters yielded substantial effects on kinematics (normalized root-mean-square-error > 10 %) compared to intact knee models, indicating surgical parameters vary post-operative knee kinematics. CONCLUSIONS: Overall, this initial study highlights the importance of surgical parameter selection on post-operative kinematics in the paediatric ACLR knee, and provides evidence of the need for personalized surgical planning to ultimately enhance patient outcomes.

Corrigendum: Study protocol for a randomized controlled trial of the RASPERA project: recalling and anticipating specific positive events to boost resilience in adolescents.

[This corrects the article DOI: 10.3389/fpubh.2023.1216988.].

Corrigendum: Study protocol for a randomized controlled trial of the RASPERA project: recalling and anticipating specific positive events to boost resilience in adolescents.

[This corrects the article DOI: 10.3389/fpubh.2023.1216988.].

Technical and clinical considerations of a physical liver phantom for CT radiomics analysis.

OBJECTIVE: This study identifies key characteristics to help build a physical liver computed tomography (CT) phantom for radiomics harmonization; particularly, the higher-order texture metrics. MATERIALS AND METHODS: CT scans of a radiomics phantom comprising of 18 novel 3D printed inserts with varying size, shape, and material combinations were acquired on a 64-slice CT scanner (Brilliance 64, Philips Healthcare). The images were acquired at 120 kV, 250 mAs, CTDIvol of 16.36 mGy, 2 mm slice thickness, and iterative noise-reduction reconstruction (iDose, Philips Healthcare, Andover, MA). Radiomics analysis was performed using the Cancer Imaging Phenomics Toolkit (CaPTk), following automated segmentation of 3D regions of interest (ROI) of the 18 inserts. The findings were compared to three additional ROI obtained of an anthropomorphic liver phantom, a patient liver CT scan, and a water phantom, at comparable imaging settings. Percentage difference in radiomic metrics values between phantom and tissue was used to assess the biological equivalency and <10% was used to claim equivalent. RESULTS: The HU for all 18 ROI from the phantom ranged from -30 to 120 which is within clinically observed HU range of the liver, showing that our phantom material (T3-6B) is representative of biological CT tissue densities (liver) with >50% radiomic features having <10% difference from liver tissue. Based on the assessment of the Neighborhood Gray Tone Difference Matrix (NGTDM) metrics it is evident that the water phantom ROI show extreme values compared to the ROIs from the phantom. This result may further reinforce the difference between a structureless quantity such as water HU values and tissue HU values found in liver. CONCLUSION: The 3-D printed patterns of the constructed radiomics phantom cover a wide span of liver tissue textures seen in CT images. Using our results, texture metrics can be selectively harmonized to establish clinically relevant and reliable radiomics panels.

Identification of allergens from Aspergillus fumigatus-Potential association with lung damage in asthma.

BACKGROUND: Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. METHODS: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti-human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. RESULTS: Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus-sensitized people with asthma, 23 non-fungal-sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose-bisphosphate aldolase class II (FBA2) (33%), NAD-dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. CONCLUSION: In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.

Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials.

BACKGROUND: Antidrug antibodies to TNF inhibitors might affect clinical outcomes. Proactive therapeutic drug monitoring allows for early detection of antidrug antibodies and might reduce negative clinical consequences. We aimed to explore how antidrug antibodies to the TNF inhibitor infliximab influence treatment outcomes, and to assess the effect of proactive therapeutic drug monitoring. METHODS: This was a predefined exploratory analysis of data from the randomised, controlled NOR-DRUM trials. The trials were conducted in rheumatology, gastroenterology, and dermatology departments at 21 Norwegian hospitals. Adult patients (aged 18-75 years) with immune-mediated inflammatory diseases were randomly assigned to proactive therapeutic drug monitoring or standard infliximab dosing in the NOR-DRUM A trial (30-week follow-up) and the NOR-DRUM B trial (52-week follow-up). Antidrug antibodies were assessed with a drug-sensitive assay before each infusion. The outcomes of remission (at week 30), disease worsening (during 52 weeks), infusion reactions, and infliximab discontinuation were assessed according to the presence of antidrug antibodies and use of therapeutic drug monitoring. FINDINGS: Between March 1, 2017, and Dec 12, 2019, 616 patients were included in the NOR-DRUM trials, of whom 615 had at least one serum infliximab and antidrug antibody assessment and were included in the present analyses. Mean age was 45 years (IQR 32-56), 305 (50%) patients were women, and 310 (50%) patients were men. Antidrug antibodies were detected in 147 (24%) patients. Remission at week 30 occurred in 25 (35%) of 72 patients with antidrug antibodies and 180 (54%) of 335 without antidrug antibodies (risk ratio 0·62 [95% CI 0·45-0·86]; p=0·0037). In patients with antidrug antibodies compared with patients without antidrug antibodies, higher rates were found for: disease worsening over 52 weeks (0·76 per person-year vs 0· 35 per person-year, hazard ratio [HR] 2·02 [95% CI 1·33-3·07]; p=0·0009), infusion reactions (0·16 per person-year vs 0·03 per person-year, HR 17·02 [6·98-41·47]; p<0·0001), and infliximab discontinuation (1·00 per person-year vs 0·20 per person-year, HR 6·64 [4·84-9·11]; p<0·0001). These associations were more pronounced in patients with high concentrations of antidrug antibodies than in those with low concentrations of antidrug antibodies. Independent of antibody status, therapeutic drug monitoring was associated with a lower risk of disease worsening (HR 0·41 [0·29-0·59]; p=0·0001) or an infusion reaction (HR 0·30 [0·12-0·73]; p=0·0076), and was associated with an increase in the rate of infliximab discontinuation (HR 1·37 [1·02-1·83]; p=0·037). INTERPRETATION: In patients where antidrug antibodies were detected, remission was less likely to be reached and sustained, and infusion reaction or discontinuation of infliximab was more likely. Timely detection of antidrug antibodies by proactive therapeutic drug monitoring facilitated treatment decisions that reduced the negative consequences, both regarding infliximab effectiveness and safety. This highlights the role of proactive therapeutic drug monitoring in optimising infliximab therapy. FUNDING: Inter-regional KLINBEFORSK grants and South-Eastern Norway Regional Health Authority grants.

Is Immunotherapy Beneficial in Patients with Oncogene-Addicted Non-Small Cell Lung Cancers? A Narrative Review.

Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody-drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as "oncogene-addiction". These "driver alterations" are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC.

Giant Response and Selectivity of Hansen Solubility Parameters-Based Graphene-SBS Co-Polymer Matrix Composite Room Temperature Sensor to Organic Vapours.

A styrene-butadiene-styrene co-polymer matrix nanocomposite filled with graphene nanoplatelets was studied to prepare chemiresistive volatile organic compounds (VOCs) room temperature sensors with considerable response and selectivity. Nanofiller concentration was estimated from the electrical conductivity percolation behaviour of the nanocomposite. Fabricated sensors provided selective relative responses to representative VOCs differing by orders of magnitude. Maximum observed average relative responses upon exposure to saturated vapours of the tested VOCs were ca. 23% for ethanol, 1600% for acetone, and the giant values were 9 × 106% for n-heptane and 10 × 106% for toluene. The insensitivity of the sensor to the direct saturated water vapour exposure was verified. Although high humidity decreases the sensor's response, it paradoxically enhances the resolution between hydrocarbons and polar organics. The non-trivial sensing mechanism is explained using the Hansen solubility parameters (HSP), enabling a rational design of new sensors; thus, the HSP-based class of sensors is outlined.

Sagittal plane knee kinematics can be measured during activities of daily living following total knee arthroplasty with two IMU.

Knee function is rarely measured objectively during functional tasks following total knee arthroplasty. Inertial measurement units (IMU) can measure knee kinematics and range of motion (ROM) during dynamic activities and offer an easy-to-use system for knee function assessment post total knee arthroplasty. However, IMU must be validated against gold standard three-dimensional optical motion capture systems (OMC) across a range of tasks if they are to see widespread uptake. We computed knee rotations and ROM from commercial IMU sensor measurements during walking, squatting, sit-to-stand, stair ascent, and stair descent in 21 patients one-year post total knee arthroplasty using two methods: direct computation using segment orientations (r_IMU), and an IMU-driven iCloud-based interactive lower limb model (m_IMU). This cross-sectional study compared computed knee angles and ROM to a gold-standard OMC and inverse kinematics method using Pearson's correlation coefficient (R) and root-mean-square-differences (RMSD). The r_IMU and m_IMU methods estimated sagittal plane knee angles with excellent correlation (>0.95) compared to OMC for walking, squatting, sit-to-stand, and stair-ascent, and very good correlation (>0.90) for stair descent. For squatting, sit-to-stand, and walking, the mean RMSD for r_IMU and m_IMU compared to OMC were <4 degrees, < 5 degrees, and <6 degrees, respectively but higher for stair ascent and descent (~12 degrees). Frontal and transverse plane knee kinematics estimated using r_IMU and m_IMU showed poor to moderate correlation compared to OMC. There were no differences in ROM measurements during squatting, sit-to-stand, and walking across the two methods. Thus, IMUs can measure sagittal plane knee angles and ROM with high accuracy for a variety of tasks and may be a useful in-clinic tool for objective assessment of knee function following total knee arthroplasty.

Real-World evidence revelations: The potential of patient support programmes to provide data on medication usage.

Patient Support Programmes (PSPs) are used by the pharmaceutical industry to provide education and support to consumers to overcome the challenges they face managing their condition and treatment. Whilst there is an increasing number of PSPs, limited information is available on whether these programmes contribute to safety signals. PSPs do not have a scientific hypothesis, nor are they governed by a protocol. However, by their nature, PSPs inevitably generate adverse event (AE) reports. The main goal of the research was to gather all Novartis-initiated PSPs for sacubitril/valsartan, followed by research in the company safety database to identify all AE reports emanating from these PSPs. Core data sheets (CDS) were reviewed to assess if these PSPs contributed to any new, regulatory-authority approved, validated signals. Overall, AEs entered into the safety database from PSPs confirmed no contribution to CDS updates. Detailed review of real-world data revealed tablet splitting or taking one higher dose tablet a day instead of twice daily. This research, and subsequent analyses, revealed that PSPs did not impact safety label changes for sacubitril/valsartan. It revealed an important finding concerning drug utilisation i.e. splitting of sacubitril/valsartan tablets to reduce cost. This finding suggests that PSPs may contribute important real-world data on patterns of medication usage. There remains a paucity of literature available on this topic, hence further research is required to assess if it would be worth designing PSPs for collecting data on drug utilisation and (lack of) efficacy. Such information from PSPs could be important for all stakeholders.

Investigating the role of imaging factors in the variability of CT-based texture analysis metrics.

OBJECTIVE: This study assesses the robustness of first-order radiomic texture features namely interquartile range (IQR), coefficient of variation (CV) and standard deviation (SD) derived from computed tomography (CT) images by varying dose, reconstruction algorithms and slice thickness using scans of a uniform water phantom, a commercial anthropomorphic liver phantom, and a human liver in-vivo. MATERIALS AND METHODS: Scans were acquired on a 16 cm detector GE Revolution Apex Edition CT scanner with variations across three different nominal slice thicknesses: 0.625, 1.25, and 2.5 mm, three different dose levels: CTDIvol of 13.86 mGy for the standard dose, 40% reduced dose and 60% reduced dose and two different reconstruction algorithms: a deep learning image reconstruction (DLIR-high) algorithm and a hybrid iterative reconstruction (IR) algorithm ASiR-V50% (AV50) were explored, varying one at a time. To assess the effect of non-linear modifications of images by AV50 and DLIR-high, images of the water phantom were also reconstructed using filtered back projection (FBP). Quantitative measures of IQR, CV and SD were extracted from twelve pre-selected, circular (1 cm diameter) regions of interest (ROIs) capturing different texture patterns across all scans. RESULTS: Across all scans, imaging, and reconstruction settings, CV, IQR and SD were observed to increase with reduction in dose and slice thickness. An exception to this observation was found when using FBP reconstruction. Lower values of CV, IQR and SD were observed in DLIR-high reconstructions compared to AV50 and FBP. The Poisson statistics were more stringently noted in FBP than DLIR-high and AV50, due to the non-linear nature of the latter two algorithms. CONCLUSION: Variation in image noise due to dose reduction algorithms, tube current, and slice thickness show a consistent trend across phantom and patient scans. Prospective evaluation across multiple centers, scanners and imaging protocols is needed for establishing quality assurance standards of radiomics.

Rising use of diagnostic imaging in Australia: An analysis of Medicare-funded radiology services between 2000 and 2021.

INTRODUCTION: The use of diagnostic imaging services is increasing worldwide. This has important impacts on healthcare resource allocation and potential risks to the population. This study aimed to quantify trends in medical imaging in Australia over the past two decades. METHODS: Data were extracted from the Australian Medicare Benefits Schedule (MBS) between 2000 and 2021. Simple linear regression analyses were performed to assess changes in absolute utilisation and utilisation rate per 100,000 population of total imaging services as well as by each imaging modality. Logistic regression analysis was performed to assess changes in total imaging services as a proportion of total Medicare services over time. Chi-squared test was used to assess for change in modality composition of imaging services. RESULTS: There were 436,255,500 imaging studies performed between 2000 and 2021. The absolute utilisation of total imaging services increased annually by an average of 864,404 (95% CI: 808,235-920,573, p < 0.001). For each consecutive year, the proportion of total Medicare services attributed to total imaging services increased by 0.01% (95% CI: 0.01-0.01, p < 0.01). There was also a statistically significant increase in the utilisation rates of imaging services per 100,000 population for each imaging modality. The number of imaging services per radiologist increased on average by 74 (95% CI: 26-122, p < 0.05) annually. CONCLUSION: The utilisation of diagnostic imaging services has increased in Australia between 2000 and 2021, outpacing the population growth, total healthcare services, and the radiologist workforce.

A Risk-Based Approach for Safety Case Follow-up of Adverse Event Reports in Pharmacovigilance.

This study presents an analysis of follow-up attempts for adverse event (AE) reports, shedding light on the characteristics of a risk-based approach to Individual Case Safety Report (ICSR) follow-up by Marketing Authorization Holders (MAH). The analysis primarily focuses on Spontaneous Reports (SR), reports from Patient Support Programs (PSPs), and literature, utilizing data from safety reports sourced from the European Economic Area (EEA) during the pre-pandemic period. Through descriptive statistics, we examine response rates spanning 1 year and compare various types of cases based on distinct ICSR features, including serious vs non-serious, listed vs unlisted, suspected vs not-suspected, SR vs PSP vs literature, as well as comparisons between different product categories (innovator, biological, generics, and combinations). The objective of this report is to stimulate further dialogue within the industry and regulatory authorities regarding the adoption of a risk-based approach to ICSR follow-up procedures.

Feasibility of a cannabidiol-dominant cannabis-based medicinal product for the treatment of long COVID symptoms: A single-arm open-label feasibility trial.

AIMS: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID. METHODS: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg δ-9-tetrahydrocannabinol/mL) per day orally. Monthly patient-reported outcome measures of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep and oxygen saturation were assessed using wearable technology. RESULTS: Twelve (1 male, 11 female) individuals diagnosed with long COVID were recruited into the trial. All participants adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of patient-reported outcome measures and daily self-report. CONCLUSION: The study drug was safe and well-tolerated, demonstrating feasibility of CBD-dominant cannabis-based medicinal products in individuals diagnosed with long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.