Profile of adverse drug reactions reported via the Continuum+ platform: Results from three-year regional follow-up.

In 2017, the Continuum+ platform was launched to provide a monitoring solution to home-based cancer care patients: AKO@dom monitoring. This platform also offers the follow-up of adverse drug reactions (ADRs) via direct notification to regional centers of pharmacovigilance (RCPVs). According to previous studies, the AKO@dom monitoring has successfully maintained treatment at the maximum effective dosage, managing ADRs and patient satisfaction. However, on the pharmacovigilance side, opinions are more divided. Due to the launch of the AKO@dom-PICTO experimentation in December 2021, in which our RCPV takes part, and to provide more data on pharmacovigilance, we decided to conduct a descriptive analysis of cases reported to our RCPV via the Continuum+ platform between 2019 and 2022. During these three years, we analyzed 1070 events, corresponding to 37 patients. Patients were primarily women (74.8%) aged around seventy with breast cancer. The most used drugs were tyrosine kinase inhibitors: palbociclib (29.7%), axitinib (16.2%), and cabozantinib (13.2%). Patients had an average of 8 ADRs, including one serious and/or unexpected ADR. Although the Continuum+ platform makes it possible to considerably limit under-reporting in pharmacovigilance, it has shortcomings. The lack of medical elements and context in notifications is a massive problem for analyzing pharmacovigilance reports. Improved access to the platform's medical information for RCPVs and pharmacovigilance training for healthcare professionals would make Continuum+ a helpful tool in pharmacovigilance.

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

In vivo depiction of cortical bone vascularization with ultra-high resolution-CT and deep learning algorithm reconstruction using osteoid osteoma as a model.

PURPOSE: The purpose of this study was to evaluate the ability to depict in vivo bone vascularization using ultra-high-resolution (UHR) computed tomography (CT) with deep learning reconstruction (DLR) and hybrid iterative reconstruction algorithm, compared to simulated conventional CT, using osteoid osteoma as a model. MATERIALS AND METHODS: Patients with histopathologically proven cortical osteoid osteoma who underwent UHR-CT between October 2019 and October 2022 were retrospectively included. Images were acquired with a 1024 × 1024 matrix and reconstructed with DLR and hybrid iterative reconstruction algorithm. To simulate conventional CT, images with a 512 × 512 matrix were also reconstructed. Two radiologists (R1, R2) independently evaluated the number of blood vessels entering the nidus and crossing the bone cortex, as well as vessel identification and image quality with a 5-point scale. Standard deviation (SD) of attenuation in the adjacent muscle and that of air were used as image noise and recorded. RESULTS: Thirteen patients with 13 osteoid osteomas were included. There were 11 men and two women with a mean age of 21.8 ± 9.1 (SD) years. For both readers, UHR-CT with DLR depicted more nidus vessels (11.5 ± 4.3 [SD] (R1) and 11.9 ± 4.6 [SD] (R2)) and cortical vessels (4 ± 3.8 [SD] and 4.3 ± 4.1 [SD], respectively) than UHR-CT with hybrid iterative reconstruction (10.5 ± 4.3 [SD] and 10.4 ± 4.6 [SD], and 4.1 ± 3.8 [SD] and 4.3 ± 3.8 [SD], respectively) and simulated conventional CT (5.3 ± 2.2 [SD] and 6.4 ± 2.5 [SD], 2 ± 1.2 [SD] and 2.4 ± 1.6 [SD], respectively) (P < 0.05). UHR-CT with DLR provided less image noise than simulated conventional CT and UHR-CT with hybrid iterative reconstruction (P < 0.05). UHR-CT with DLR received the greatest score and simulated conventional CT the lowest score for vessel identification and image quality. CONCLUSION: UHR-CT with DLR shows less noise than UHR-CT with hybrid iterative reconstruction and significantly improves cortical bone vascularization depiction compared to simulated conventional CT.

Increasing Collagen to Bioink Drives Mesenchymal Stromal Cells-Chondrogenesis from Hyaline to Calcified Layers.

The bioextrusion of mesenchymal stromal cells (MSCs) directly seeded in a bioink enables the production of three-dimensional (3D) constructs, promoting their chondrogenic differentiation. Our study aimed to evaluate the effect of different type I collagen concentrations in the bioink on MSCs' chondrogenic differentiation. We printed 3D constructs using an alginate, gelatin, and fibrinogen-based bioink cellularized with MSCs, with four different quantities of type I collagen addition (0.0, 0.5, 1.0, and 5.0 mg per bioink syringe). We assessed the influence of the bioprinting process, the bioink composition, and the growth factor (TGF-ꞵ1) on the MSCs' survival rate. We confirmed the biocompatibility of the process and the bioinks' cytocompatibility. We evaluated the chondrogenic effects of TGF-ꞵ1 and collagen addition on the MSCs' chondrogenic properties through macroscopic observation, shrinking ratio, reverse transcription polymerase chain reaction, glycosaminoglycan synthesis, histology, and type II collagen immunohistochemistry. The bioink containing 0.5 mg of collagen produces the richest hyaline-like extracellular matrix, presenting itself as a promising tool to recreate the superficial layer of hyaline cartilage. The bioink containing 5.0 mg of collagen enhances the synthesis of a calcified matrix, making it a good candidate for mimicking the calcified cartilaginous layer. Type I collagen thus allows the dose-dependent design of specific hyaline cartilage layers.

Computed Tomography Bone Imaging: Pushing the Boundaries in Clinical Practice.

Bone microarchitecture has several clinical implications over and above estimating bone strength. Computed tomography (CT) analysis mainly uses high-resolution peripheral quantitative CT and micro-CT, research imaging techniques, most often limited to peripheral skeleton assessment. Ultra-high-resolution (UHR) CT and photon-counting detector CT, two commercially available techniques, provide images that can approach the spatial resolution of the trabeculae, bringing bone microarchitecture analysis into clinical practice and improving depiction of bone vascularization, tumor matrix, and cortical and periosteal bone. This review presents bone microarchitecture anatomy, principles of analysis, reference measurements, and an update on the performance and potential clinical applications of these new CT techniques. We also share our clinical experience and technical considerations using an UHR-CT device.

Non-medical use of baclofen: A case series and review of the literature.

BACKGROUND: Baclofen is widely used for spastic disorders and, most recently, for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study aims to assess the motives, diversion sources, and routes of administration associated with the non-medical use of baclofen and examine health problems related to the non-medical use of baclofen. METHODS: Spontaneous reports of baclofen abuse reported to the addictovigilance centre of East France were analysed. A literature search was conducted using PubMed®, Web of Sciences®, and Google Scholar® databases. Both investigations were performed in February 2021 without a time limit. RESULTS: Forty-six cases were analysed (33 from the literature review and 13 from the addictovigilance base). Baclofen's non-medical use mainly affected male subjects with addictive history, but issues of primary abuse in subjects without any substance abuse history were also observed. Euphoria search was the most common reason for misuse. The route of administration included oral, snorting, and sublingual use. Some cases involving illegal sources were also observed. Most patients misusing baclofen presented severe complications, mainly represented by neurological and respiratory disturbances. Physical and psychological dependence on baclofen was observed in three persons. CONCLUSIONS: Although baclofen abuse remains relatively infrequent or (most likely) underestimated, this study helped confirm baclofen's intrinsic abuse potential and make visible the baclofen-abuse-related health visible harms. Careful consideration and benefit-risk analysis should be employed when prescribing baclofen, and emergency departments should be aware of baclofen dangers in abuse situations.

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis. METHODS: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated. RESULTS: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions. CONCLUSIONS: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis. CLINICAL TRIAL REGISTRATION: NCT02250729.

COVID-19 Vaccination and the Incidence of De Novo or Recurrent Rheumatoid Arthritis: A French and International (VigiBase) Signal Detection Study.

COVID-19 vaccination is critical in frequently immunocompromised patients with rheumatoid arthritis (RA). However, there is a question about the risk of RA flares following vaccination. Our study intended to find out about cases of new RA or flare-ups in people who already had RA that were reported in French and international pharmacovigilance databases after COVID-19 vaccination. We performed a "case-noncase" method in the international pharmacovigilance database VigiBase to identify the risk of RA following COVID-19 vaccination compared with other nonlive vaccines. Using the French Pharmacovigilance Database (FPVD), a descriptive analysis was carried out for RA cases after COVID-19 immunization and a multivariate logistic regression analysis was conducted to compare variables in the new-onset vs. flare-up groups. In 2021, 2,387 cases of RA were reported from 2,817,902 adverse drug reactions associated with COVID-19 vaccines recorded in VigiBase. The reporting odds ratio of RA onset with COVID-19 vaccines compared with the other nonlive vaccines was 0.66 (P < 0.0001). The FPVD reported 161 cases of RA with COVID-19 vaccines, including 77 new-onset RA and 84 cases of RA flare-up. In 88 cases (84.7%), RA occurred after the first dose. The mean time between vaccination and disease onset was 14 ± 21 days, and the delay was significantly shorter in the flare-up group. We do not show a higher risk of RA after COVID-19 vaccination compared with other nonlive vaccines in adults. De novo RA was more likely to happen quickly, be more severe, and have a worse outcome than flares in patients with RA.

Radiological evolution of progestogen-induced meningioma: A monocentric retrospective study.

Cyproterone acetate (CPA) is known to induce meningioma, and recently, nomegestrol acetate (NMA) and chlormadinone acetate (CMA) were also involved. Progestagen-induced meningioma management starts with progestogen discontinuation and is either interventional (surgery and/or radiotherapy) or conservative (clinical and MRI radiological follow-up). We performed a retrospective volumetric radiological outcomSe study of progestogen-induced meningiomas diagnosed in our hospital. We analysed progestogen-related meningiomas diagnosed until 30 June 2021, with at least one diagnostic and one follow-up MRI results. Meningioma volumes were centrally retrospectively measured using a T1-weighted 3D millimeter sequence with gadolinium injection on a postprocessing console. We analysed 98 meningiomas of 38 females and one transgender (male-to-female), of which 25 (64.1%) had taken CPA, seven (17.9%) NMA, three (7.7%) CMA, and four (10.2%) several progestogens. Eleven patients (24 meningiomas) underwent interventional management, seven patients had meningiomas followed by conservative or interventional management, and 21 patients (51 meningiomas) had only conservative management. Of these 21 patients, 17 had discontinued their progestogen less than 6 months before, of which 14 (82.3%) had decreased or stable meningioma(s) during a 24-month median follow-up (3 to 75) period. Overall, four of the 39 patients experienced meningioma progression (three during conservative treatment and one after surgery), including two patients who had continued NMA or CMA treatment several years after diagnosis. Our study confirms a generally favourable outcome of progestogen-related meningioma after conservative treatment, especially for CPA. It also underlines the need for progestogen discontinuation at meningioma diagnosis.

Drug-induced radiation recall reactions and non-anticancer drugs: A descriptive analysis from VigiBase®.

Radiation recall reactions are inflammatory reactions confined to previously irradiated tissues, often of drug-induced etiology, particularly with anticancer therapies. Other drugs, in particular COVID-19 vaccines, may also be involved. To describe radiation recall reactions under non-anticancer drugs more precisely, we extracted the cases of radiation recall reactions associated with non-anticancer drugs from WHO pharmacovigilance database VigiBase®. We performed two analyses from this extraction: a global analysis and an analysis focusing on vaccination-related issues. We extracted 120 cases corresponding to 269 drugs, of which 130 were non-anticancer (22 vaccines). Among the non-anticancer drugs, tozinameran was the most reported treatment (4.46% of cases), followed by levofloxacin (2.97%) and folinic acid (2.60%), dexamethasone (2.23), and ChAdOx1 nCoV-19 vaccine and prednisone (1.86% each). Among vaccines, tozinameran (54.55% of cases) was the most reported, followed by ChAdOx1 nCoV-19 (22.73%), HPV and inactivated influenza vaccine (9.09% each), and elasomeran (4.55%). Our study first describes the occurrence of radiation recall reactions during non-anticancer treatment. It also highlights a potential safety signal with COVID-19 vaccines.

Imaging in Hip Arthroplasty Management Part 2: Postoperative Diagnostic Imaging Strategy.

Hip arthroplasty (HA) is a frequently used procedure with high success rates, but 7% to 27% of the patients complain of persistent postsurgical pain 1 to 4 years post-operation. HA complications depend on the post-operative delay, the type of material used, the patient's characteristics, and the surgical approach. Radiographs are still the first imaging modality used for routine follow-up, in asymptomatic and painful cases. CT and MRI used to suffer from metallic artifacts but are nowadays central in HA complications diagnosis, both having their advantages and drawbacks. Additionally, there is no consensus on the optimal imaging workup for HA complication diagnosis, which may have an impact on patient management. After a brief reminder about the different types of prostheses, this article reviews their normal and pathologic appearance, according to each imaging modality, keeping in mind that few abnormalities might be present, not anyone requiring treatment, depending on the clinical scenario. A diagnostic imaging workup is also discussed, to aid the therapist in his imaging studies prescription and the radiologist in their practical aspects.

Rat synovial tissue and blood rapamycin pharmacokinetics after intra-articular injection of free solution or nanoparticles vs free rapamycin intravenous shot.

Intra-articular (IA) injection of a chondroprotective candidate may delay the osteoarthritis (OA) course, but its rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics (PK) of IA rapamycin injected as sustained release in nanoparticles (NPs) versus a free rapamycin suspension in the rat knee compared to an intravenous (IV) free rapamycin shot taken as a reference. Rats received either a single IV injection of free rapamycin (10 µM) or an IA of free or NPs-loaded rapamycin. After sequential exsanguination (15, 30, 60, 180, 360 min, D1, and D7), knee synovial tissue (ST) and cartilage histology were performed. Blood and ST concentrations (LC-MS/MS), PK parameters (area under the curve: AUC; mean residence time: MRT; elimination half-life: T1/2), and IA biocompatibility were assessed. AUCIV was significantly higher for IV than for both IA injections (AUCIA free and AUCIA NPs), with 4248 vs 28 and 74 µg.min.L-1. For ST parameters, we observed a significant difference between AUCIA free and AUCIA NPs with 3735 and 10513 µg.min.L-1 correspondingly. Articular T1/2 and MRT were higher after NPs than after free rapamycin injection: 57.8 and 5.0 h for T1/2 and 80.6 and 5.5 h for MRT, respectively. Histological analysis revealed no chondral injuries and slight transient synovitis only 3 h after the administration of NPs. In the rat knee, rapamycin-loaded NPs delivery via a single IA injection is biocompatible and prolongs synovium joint residency, diminishes blood levels, and reduces detrimental systemic exposure.

Adverse effects of gender-affirming hormonal therapy in transgender persons: Assessing reports in the French pharmacovigilance database.

Limited data are available on adverse drug reactions (ADRs) of gender-affirming hormone therapy (HT), mainly due to the lack of population-based studies with adequate controls, thus making spontaneous reporting systems a valuable tool to detect potential side reactions. In this nationwide retrospective study, we aimed to analyze ADRs related to gender-affirming HT reported in the French pharmacovigilance database (FPVD). We requested all the individual case safety reports related to gender-affirming HT recorded in the FPVD before May 27, 2020. We excluded previously published cases and those where gender-affirming HT was not the suspected drug. A total of 28 reports of ADRs were identified. Six concerned transgender men (21-40 years) and 22 transgender women (22-68 years). In transgender men taking testosterone enanthate, all reported ADRs were cardiovascular events, with pulmonary embolism in 50% of cases. Median time to onset (TTO) was 34 months. In transgender women, antiandrogens, mainly cyproterone acetate, were involved in 68% of cases, and estrogens in 77% of cases, mostly in association with progestin or cyproterone acetate. Meningiomas were the principal ADRs, followed by cardiovascular events, with a median TTO of 5.3 months. Our data show a previously unreported, non-negligible proportion of cases indicating cardiovascular ADRs in transgender men younger than 40 years. In transgender women, cardiovascular events were the second most frequent ADR. Further research is necessary to identify risk factors that might help to the individualization of treatment strategies. There is a necessity to increase awareness, implement preventive and education measures.

Gastroenterological safety of IL-17 inhibitors: a systematic literature review.

INTRODUCTION: Interleukin 17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of many chronic immune-mediated disorders. Interleukin 17 inhibitors provide an excellent treatment option for patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. However, Interleukin 17 inhibitors have been suspected of worsening or triggering new-onset inflammatory bowel disease. AREAS COVERED: A literature search was conducted until March 2021 to investigate reporting prevalence, and characteristics of all gastroenterological adverse events in patients treated with Interleukin 17 inhibitors. One hundred and six clinical randomized trials were included, involving 40,053 patients. Inflammatory bowel disease cases were reported in 0.4% of patients exposed to Interleukin 17 inhibitors. The most frequent other gastrointestinal adverse events were diarrhea (2.5%), nausea or vomiting (0.7%), and gastroenteritis (0.2%). Sixty-one uncontrolled or retrospective studies were included, involving 16,791 patients. Sixty (0.36%) inflammatory bowel disease cases were reported, 0.6% of patients reported other gastrointestinal adverse events. EXPERT OPINION: Interleukin 17 inhibitors are safe and effective in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Low incidence rate of developing new-onset inflammatory bowel disease or exacerbating preexisting inflammatory bowel disease with anti-IL-17 agents has been reported. Clinicians should be aware of the possibility of these concerns when considering this therapy.

Rapamycin-loaded Poly(lactic-co-glycolic) acid nanoparticles: Preparation, characterization, and in vitro toxicity study for potential intra-articular injection.

Osteoarthritis (OA) is the most common degenerative joint disease. Rapamycin is a potential candidate for OA treatment by increasing the autophagy process implicated in its physiopathology. To optimize Rapamycin profit and avoid systemic side effects, intra-articular (i.a.) administration appeared helpful. However, Rapamycin's highly hydrophobic nature and low bioavailability made it challenging to develop purpose-made drug delivery systems to overcome these limitations. We developed Rapamycin-loaded nanoparticles (NPs) using poly (lactic-co-glycolic acid) by emulsion/evaporation method. We evaluated these NPs' cytocompatibility towards cartilage (chondrocytes) and synovial membrane cells (synoviocytes) for a potential i.a. administration. The in vitro characterization of Rapamycin-loaded NPs had shown a suitable profile for an i.a. administration. In vitro biocompatibility of NPs was highlighted to 10 µM of Rapamycin for both synoviocytes and chondrocytes, but significant toxicity was observed with higher concentrations. Besides, synoviocytes are more sensitive to Rapamycin-loaded NPs than chondrocytes. Finally, we observed in vitro that an adapted formulated Rapamycin-loaded NPs could be safe at suitable i.a. injection concentrations. The toxic effect of Rapamycin encapsulated in these NPs on both articular cells was dose-dependent. After Rapamycin-loaded NPs i.a. administration, local retention, in situ safety, and systemic release should be evaluated with experimental in vivo models.

Outcome Improvement Between the First Two Waves of the Coronavirus Disease 2019 Pandemic in a Single Tertiary-Care Hospital in Belgium.

OBJECTIVES: To compare patient management and outcome during the first and second waves of the coronavirus 2019 pandemic. DESIGN: Single-center prospective cohort study. SETTING: Tertiary-care University Hospital. PATIENTS: All adult patients admitted in either the first (from March 15 to May 15, 2020) or second (from October 1 to November 30, 2020) wave of coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was 30-day mortality. During the second wave of the coronavirus disease 2019 pandemic, 33 patients (4.8%) were transferred due to overcrowding and excluded from analysis. There were 341 (first wave of the coronavirus disease 2019 pandemic) and 695 (second wave of the coronavirus disease 2019 pandemic) coronavirus disease 2019 patients admitted to the hospital, with median age first wave of the coronavirus disease 2019 pandemic as 68 (57-80) and second wave of the coronavirus disease 2019 pandemic as 71 (60-80) (p = 0.15), and similar admission severity. For the first wave of the coronavirus disease 2019 pandemic versus second wave of the coronavirus disease 2019 pandemic, 30-day mortality was 74/341 (22%) and 98/662 (15%) (p = 0.007). In the ward, 11/341 (3.2%) and 404/662 (61%) received dexamethasone (p < 0.001); 6/341 (2%) and 79/662 (12%) received high-flow nasal oxygen (p < 0.0001); 2/341 (0.6%) and 88/662 (13.3%) received remdesivir (p < 0.0001); 249/341 (73%) and 0/662 (0%) received hydroxychloroquine (p < 0.0001); and 87/341 (26%) and 128/662 (19%) (p = 0.024) patients were transferred to ICU. On ICU admission, median Sequential Organ Failure Assessment was 6 (3-7) and 4 (3-6) (p = 0.02). High-flow nasal oxygen was given to 16/87 (18%) and 102/128 (80%) (p < 0.001); 69/87 (79%) and 56/128 (44%) received mechanical ventilation (p < 0.001) with durations 17 days (10-26 d) and 10 days (5-17 d) (p = 0.01). Median ICU length of stay was 14 days (5-27 d) and 6 days (3-11 d) (p < 0.001). Finally, 16/87 (18%) and 8/128 (6%) received renal replacement therapy (p = 0.0055); and 64/87 (74%) and 51/128 (40%) needed vasopressor support (p < 0.001). CONCLUSIONS: The main therapeutic changes between the first wave of the coronavirus disease 2019 pandemic and the second wave of the coronavirus disease 2019 pandemic were use of steroids, unrestrictive use of high-flow nasal oxygen for hypoxemic patients, and transfer of patients to other geographic areas in the case of ICU overcrowding. These changes were associated with a decrease in 30-day mortality, ICU admission, and organ support.

IL-17 Inhibitors and Inflammatory Bowel Diseases: A Postmarketing Study in Vigibase.

Several gastrointestinal symptoms and chronic inflammatory bowel diseases (IBDs) have been reported after therapy with IL-17 inhibitors. To date, however, no study has shown a clear association between these drugs and IBD onset. We searched on Vigibase, the worldwide pharmacovigilance database, to investigate reporting prevalence, characteristics, and prognosis of all gastroenterological adverse events in patients treated with IL-17 inhibitors. In total, 1,129 gastrointestinal Individual Case Safety Reports (ICSRs) were identified, including 850 IBD (42.5% Crohn's disease, 31.9% ulcerative colitis, and 25.6% undifferentiated IBD) and 279 colitis (mainly undifferentiated colitis (79.2%), and microscopic colitis (10.4%)). ICSRs were associated with secukinumab (SEC, 83.6%) or ixekizumab (IXE, 16.3%), whereas only one colitis occurred with brodalumab (0.1%). Most IBD and colitis cases were detected within 6 months from therapy start in both the SEC (68.8% and 73.5%) and IXE groups (100% and 66.7%). Patients' outcomes were reported in 428 ICSRs (37.9%). Complete or ongoing recovery from symptoms was detected in about two-thirds of patients experiencing IBD (59.5%) or colitis (64.2%), whereas in the other cases, there was no recovery (33.9% and 29.5%) or there were sequelae (5.4% and 4.2%). Fatal events occurred in four patients (1.2%) in the IBD group (3 after SEC and on1e with IXE) and two SEC-treated subjects in the colitis group (2.1%). Treatment with IL-17 inhibitors is associated with a relevant number of exacerbations and new onset of IBD and colitis. Careful evaluation of gastrointestinal symptoms and the monitoring of intestinal inflammatory biomarkers should be recommended before prescribing these drugs.

Drug adulteration of sexual enhancement supplements: a worldwide insidious public health threat.

Worldwide, the consumption of dietary supplements for the enhancement of sexual performance is common. Consumers are generally fond of these products because they often want to avoid drugs, preferring "natural" than "chemical" solutions. This is challenging, as many of these supplements labelled "herbal" or "natural" are actually adulterated with drugs, mainly phosphodiesterase-5 inhibitors. This phenomenon is facilitated by fewer demanding regulations for marketing supplements. Thus, consumers may be widely exposed to serious adverse events, such as acute liver injury, kidney failure, pulmonary embolism, stroke or even death. We aim to warn physicians about this issue. This multidisciplinary review simultaneously deals with clinical consequences of this phenomenon, analytical toxicology and regulation. Indeed, after outlining this worldwide issue and highlighting that a drug-adulterated dietary supplement is actually a falsified drug, we discuss its main contributing factors. Then, we describe some examples of adverse events of which a case of sildenafil-tadalafil-induced ischaemic stroke that benefited medical care in our hospital. Furthermore, we present some means to avoid adulteration and discuss their limitations that may be explained by the heterogeneity of the regulation of dietary supplements between countries. Doing so, we point out the requirement of a global harmonization of this regulation for an efficient eradication of this public health threat. Meanwhile, dietary supplements should be considered adulterated until proven otherwise. Thus, we encourage physicians to investigate these products in the drug histories of their patients, especially when clinical conditions cannot be explained by classical aetiologies.