Conversion of waste poly(vinyl chloride) to branched polyethylene mediated by silylium ions.

Full dechlorination of poly(vinyl chloride) (PVC) in a controlled manner to yield useful polymeric and chlorinated products is of great interest for the processing of PVC waste. Forming polyethylene (PE) without corrosive by-products would allow for a pre-treatment of PE wastes that are often contaminated with PVC. Herein, full dechlorination of PVC has been achieved via generation of silylium ions in situ, to furnish PE products. Complete dechlorination of PVC can be achieved in 2 hours, yielding organic polymer that has similar spectroscopic and thermal signatures of branched PE, with no observable chlorine. The degree of branching can be tuned between 31 and 57 branches per 1000 carbons, with melting temperatures ranging from 51 to 93 °C. This method is applicable to not only pure PVC, but also commercial PVC products. Depending on if the PVC products are separated from plasticizers, different melting points of the resulting PE are observed. PVC dechlorination in the presence of PE waste is also shown. This is the first report of being able to cleanly convert PVC waste to PE in high yields and tune the thermal properties of the PE product, highlighting the remarkable control that silylium ion mediated transformations enables compared to past chemical methods.

Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks.

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy. METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale (ratings range from "much worse" to "much better") at two or more consecutive time points within 12 hours after the first administration of the trial agent. Key secondary end points, assessed in a time-to-event analysis, were a reduction in attack severity (an improved rating on the Patient Global Impression of Severity [PGI-S] scale, with ratings ranging from "none" to "very severe") at two or more consecutive time points within 12 hours and complete attack resolution (a rating of "none" on the PGI-S scale) within 24 hours. RESULTS: A total of 136 participants were assigned to one of six trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief with the 300-mg dose and the 600-mg dose was faster than with placebo (P<0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively. The time to reduction in the attack severity with the 300-mg dose and the 600-mg dose was faster than with placebo (P = 0.004 and P = 0.003), with median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12). The time to complete resolution was faster with the 300-mg and 600-mg doses than with placebo (P = 0.002 and P<0.001). The percentage of attacks with complete resolution within 24 hours was 42.5% with the 300-mg dose, 49.5% with the 600-mg dose, and 27.4% with placebo. Sebetralstat and placebo had similar safety profiles; no serious adverse events related to the trial agents were reported. CONCLUSIONS: Oral sebetralstat provided faster times to the beginning of symptom relief, reduction in attack severity, and complete attack resolution than placebo. (Funded by KalVista Pharmaceuticals; KONFIDENT ClinicalTrials.gov number, NCT05259917; EudraCT number, 2021-001226-21.).

Hereditary angioedema with normal C1-inhibitor: Clinical and genetic characterization of 15 Portuguese unrelated families.

BACKGROUND: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease with similar phenotype to HAE-C1-INH but different genetic background. Currently, 6 subtypes are recognized, based on the underlying mutations. Several aspects need further clarification. OBJECTIVE: To assess clinical features of patients with genetically characterized HAE-nC1-INH from the North of Portugal. METHODS: Retrospective assessment of clinical data from all patients with HAE-nC1-INH followed at a HAE Reference Center. RESULTS: A total of 41 patients were identified, 4 with no family history. The FXII mutation Thr328Lys (38 carriers) was the most prevalent. There were 3 new potentially disease-causing variants linked to HAE-nC1-INH identified (c.529+4A>G:FXII; Cys248*:Kininogen-1; and Arg261His:Plasminogen). The HAE-FXII cohort included 82% females and 71.8% symptomatic patients. Penetrance rate was significantly higher in females (81.3% vs 28.6%; P = .012). A hormonal influence was observed in 96.2% of the symptomatic females, although 62.5% remained symptomatic after oral estrogen withdrawal. Trauma and dental procedures were frequent triggers (82.6% and 45.5%, respectively). Main locations were facial (described by 96%), lips (82.1%), and eyelids (64.3%). One patient reported erythema marginatum as prodrome. Plasma-derived C1-INH was effective as short-term prophylaxis in all treated patients, but only in 80% as on-demand treatment. Icatibant was effectively used on demand in 9 patients, but with relapses in 5 (57%). CONCLUSION: We described a large Portuguese series of patients with HAE-nC1-INH genetically characterized. Differences with others may contribute to improve current unmet needs and raise awareness of this rare disease. We highlighted the identification of 3 new variants (additional molecular studies are ongoing) and the report of erythema marginatum in HAE-nC1-INH.

Dietary parameters in patients with drug allergy: Assessing dietary inflammatory index.

BACKGROUND: Research on the increasing incidence of allergic diseases evidenced the role of diet as a potential key factor. Diet can modulate the low-grade systemic inflammation related to obesity and several diseases. There are no published data on drug allergy. AIM: To investigate a potential association between diet, including dietary inflammatory index (DII), and drug allergy. Also, to evaluate correlations between diet and obesity, inflammatory and metabolic parameters in patients with drug allergy. METHODS: Ninety consecutive patients studied for suspected drug allergy were evaluated in terms of dietary parameters, anthropometric measurements, bioimpedance and biochemical analysis. DII was calculated based on information collected from a food frequency questionnaire. RESULTS: After diagnostic work-up, 39 patients had confirmed drug allergy and 45 excluded, representing the study group and the control group, respectively. The majority (79%) were female, with mean age of 39.58±13.3 years. The 84 subjects revealed an anti-inflammatory diet pattern. No significative difference was found in DII scores between drug allergic patients and controls (-3.37±0.95 vs -3.39±0.86, p = 0.985). However, the patients with drug allergy revealed higher obesity and inflammatory parameters. A significative negative correlation was found between DII and adiponectin levels, in the control group (r = -0.311, p = 0.040). In the patient group, a significative positive correlation was observed between DII and triglycerides (r = 0.359, p = 0.032). No other correlations were found between DII and the assessed parameters. Patients with drug allergy presented a significative higher intake of mono-unsaturated fatty-acids comparing to controls (19.8±3.7 vs 17.8 ± 4.0, p = 0.021). No other statistically significant differences were achieved in dietary parameters, between patients and controls. CONCLUSION: The population assessed in this study revealed an anti-inflammatory diet profile. Although we have found in a previous work that the same patients with drug allergy revealed higher obesity and inflammatory parameters, the DII did not allow to distinguish between patients with drug allergy or controls. The DII scores correlated with triglycerides levels in the drug allergy patients and inversely with adiponectin levels in the control group. Larger studies are needed to clarify the potential role of the diet in drug allergy and its outcomes.

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication.

Reported cases of anaphylaxis following COVID-19 vaccination raised concerns about the safety of these vaccines, namely in patients suffering from clonal mast cell (MC) disorders-a heterogenous group of disorders in which patients may be prone to anaphylaxis caused by vaccination. This study aimed to assess the safety of COVID-19 vaccines in patients with clonal MC disorders. We performed an ambidirectional cohort study with 30 clonal MC disorder patients (n = 26 in the prospective arm and n = 4 in the retrospective arm), that were submitted to COVID-19 vaccination. Among these, 11 (37%) were males, and median age at vaccination date was 41 years (range: 5y to 76y). One patient had prior history of anaphylaxis following vaccination. Those in the prospective arm received a premedication protocol including H1- and H2-antihistamines and montelukast, while those in the retrospective arm did not premedicate. Overall, patients received a total of 81 doses, 73 under premedication and 8 without premedication. No MC activation symptoms were reported. COVID-19 vaccination seems to be safe in patients with clonal mast cell disorders, including those with prior anaphylaxis following vaccination. Robust premedication protocols may allow for vaccination in ambulatory settings.

Patterns of dosage regimen instructions regarding topical medicines: how is the information perceived by patients?

BACKGROUND: The communication of dosage regimen instructions by physicians is of utmost importance on treatment adherence. Few studies until now have approached the topical treatment adherence subject. OBJECTIVE: This study aims the characterization of dosage regimen instructions given by physicians and the assessment of chronic dermatological patients' perception regarding these instructions. METHODS: Two instruments one for physicians (PHYSDOSAGE) and one for patients (PATIENTDOSAGE) were developed and applied in a cross-sectional, descriptive and exploratory study to two independent samples composed by 91 physicians and 43 patients. RESULTS: Most of physicians reported to provide dosage regimen instructions. When cross checking information from both studied samples, physicians and patients, it was concluded that physicians reported to provide more frequently oral and written treatment instructions, e.g. electronic prescription, than patients reported having received it. Also, physicians claimed to often provide information about the duration of treatment and the frequency of topical medicines' application, which was not acknowledged by patients. CONCLUSIONS: Contradictory results were found between the physicians' information input and the patients' perception about dosage regimen instructions provided during the consultation. These findings could negatively influence the treatment adherence and the clinical outcomes. Thus, it is of paramount importance the implementation of strategies to improve optimal communication of dosage regimen instructions for topical medicines.

Obesity markers in patients with drug allergy and body fat as a predictor.

BACKGROUND: Obesity is a chronic low-grade inflammation state associated with several diseases. OBJECTIVE: To investigate a potential link between drug allergy and obesity, exploring whether the association depends on the type (immediate vs nonimmediate) or the severity of the reaction. METHODS: Anthropometric measurements, bioimpedance, and biochemical analysis, including serum adipokines, were performed in 90 consecutive adult patients studied for suspected drug allergy. Logistic regression models were developed to identify predictors of drug allergy. RESULTS: A total of 84 patients completed the diagnostic workup (78.6% women; mean age 39.58 ± 13.3 years). Drug allergy was confirmed in 39 patients and excluded in 45 (controls). Regarding body mass index, 42.2% had normal weight and 55.3% were overweight/obese. A total of 58% of women and 41% of men fulfilled the criteria for central obesity. Patients with drug allergy exhibited considerably higher body mass index, waist and hip circumferences, waist-hip ratio, fat mass, body fat percentage (BFP), trunk fat mass, leptin levels, and leptin-adiponectin ratio than controls. Similar results were obtained in the subgroup with immediate reactions, compared with the nonimmediate or unknown reactions. The higher the BFP and the number of reactions, the greater the odds of drug allergy (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.14 and OR, 2.82; 95% CI, 1.31-6.10, respectively). An immediate reaction was also a predictor of drug allergy (OR, 3.81; 95% CI, 1.30-11.14, P = .02), compared with nonimmediate or unknown reactions. In patients with drug allergy, BFP was a predictor of having an immediate reaction (OR, 1.12; 95% CI, 1.02-1.24, P = .02). CONCLUSION: Our study illustrates, for the first time, evidence of a link between obesity and drug allergy, particularly immediate reactions. The BFP emerged as a potential predictor of drug allergy.

Psychological profiles of patients with suspected drug allergy.

BACKGROUND: Several studies demonstrate an important association between allergic diseases and patients' psychological characteristics. OBJECTIVE: To evaluate any differences in the psychological characteristics of patients studied for suspected drug allergy in comparison with healthy controls. A secondary aim was to assess differences between patients with confirmed versus excluded drug allergy, with respect to the clinical aspects. METHODS: The psychological characteristics of 115 consecutive patients >16 years-old, studied for suspected drug allergy were assessed. They were compared with healthy controls. Four validated questionnaires were used to evaluate anxiety, depression, alexithymia, and personality type. RESULTS: Eighty-eight patients completed the evaluation: 34 had confirmed drug allergy and 33 excluded. Forty-eight healthy subjects filled the 4 questionnaires. Increased neuroticism was associated with increased odds of belonging to the excluded drug allergy group (odds ratio [OR], 1.374; 95% confidence interval [CI], 1.173-1.609). Increased neuroticism (OR, 1.244; 95% CI, 1.065-1.453) and increased anxiety (OR, 1.210; 95% CI, 1.084-1.351) were associated with increased odds of confirmed drug allergy. However, higher extraversion decreased this likelihood (OR, 0.755; 95% CI, 0.643-0.888). The odds of having confirmed drug allergy was reduced by 79.7% (OR, 0.203; 95% CI, 0.060-0.694) for patients with 2 suspected drugs and by 84.6% (OR, 0.154; 95% CI, 0.029-0.809) for those with ≥3 in comparison to those with only one. Patients with moderate to severe reactions were more likely to have confirmed drug allergy (OR, 4.295; 95% CI, 1.105-16.693) than those with milder manifestations. CONCLUSION: Our results highlight that patients with drug allergy have a distinctive psychological profile. Psychological assessment may help to identify patients that would benefit from a targeted intervention.

Overview of Drug Allergy: From Immunogenetic Basis to Practice.

Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.

A terapêutica farmacológica consiste, frequentemente, num equilíbrio entre os efeitos benéficos e prejudiciais dos fármacos. As reações alérgicas a fármacos são reações adversas mediadas por mecanismos imunológicos e não relacionadas com as ações farmacológicas do fármaco. Podem ser classificadas quer com base na apresentação clínica, quer no mecanismo imunológico subjacente. Embora pouco comuns, as reações alérgicas a fármacos são imprevisíveis, podendo ser graves e potencialmente fatais. O objetivo da presente revisão da literatura foi disponibilizar aos clínicos de diversas áreas médicas uma ferramenta de trabalho para uma melhor abordagem dos seus doentes com suspeita de alergia a fármacos. Foi conduzida de forma não sistemática e procura descrever a complexidade das reações alérgicas a fármacos, desde a fisiopatologia à heterogeneidade da apresentação clínica. Foi dado especial destaque aos fármacos mais frequentemente envolvidos, à classificação das reações e aos fatores de risco. Apesar de todos os avanços nesta área desafiante e complexa da alergologia e imunologia clínica, a alergia a fármacos não está ainda completamente compreendida e estabelecida. A farmacogenética trouxe um contributo excecional, embora apenas para um número muito limitado de fármacos esteja definida uma associação farmacogenética. São necessários estudos adicionais que permitam obter respostas mais diretas na abordagem de cada caso individual de alergia a fármacos.

Type B adverse drug reactions reported by an immunoallergology department.

OBJECTIVE: Characterization of the adverse drug reactions (ADR) reported by the immunoallergology department (IAD), Centro Hospitalar de São João (Porto), to the Northern Pharmacovigilance Centre (NPC). METHODS: An observational, descriptive and retrospective study was conducted, based in a spontaneous report system. Participants were all the patients from the IAD, with suspected ADR, reported to NPC by specialists after the study was completed. RESULTS: Studied population had a median age of 41 years, with the predominance of the female gender (73.2%). Allergic rhinitis and asthma were the most frequent comorbidities. All studied ADR were type B, 89.6% were serious, 86.4% unexpected and 2.6% associated with drugs that presented less than 2 years in the market. The most represented drug classes were the non-steroidal anti-inflammatory drugs (NSAIDs) (52.6%) and antibiotics (25.2%). Skin symptoms represented 61.2% of the reported complaints. About 52.9% of these ADR occurred in less than one hour after intake. The most frequent ADR treatment at the time of the reaction was drug interruption (86.2%), followed by the prescription of anti-histamines (42.2%). CONCLUSIONS: Reported ADR to NPC by the Drug Alert Unit were mainly serious, unexpected, associated with NSAIDs and antibiotics and related with marketing authorization medicines older than two years. These results could be very useful to develop strategies to prevent the clinical and economic consequences of ADR.

Type B adverse drug reactions reported by an immunoallergology department

Objective: Characterization of the adverse drug reactions (ADR) reported by the immunoallergology department (IAD), Centro Hospitalar de São João (Porto), to the Northern Pharmacovigilance Centre (NPC). Methods: An observational, descriptive and retrospective study was conducted, based in a spontaneous report system. Participants were all the patients from the IAD, with suspected ADR, reported to NPC by specialists after the study was completed. Results: Studied population had a median age of 41 years, with the predominance of the female gender (73.2%). Allergic rhinitis and asthma were the most frequent comorbidities. All studied ADR were type B, 89.6% were serious, 86.4% unexpected and 2.6% associated with drugs that presented less than 2 years in the market. The most represented drug classes were the non-steroidal anti-inflammatory drugs (NSAIDs) (52.6%) and antibiotics (25.2%). Skin symptoms represented 61.2% of the reported complaints. About 52.9% of these ADR occurred in less than one hour after intake. The most frequent ADR treatment at the time of the reaction was drug interruption (86.2%), followed by the prescription of anti-histamines (42.2%). Conclusions: Reported ADR to NPC by the Drug Alert Unitwere mainly serious, unexpected, associated with NSAIDs and antibiotics and related with marketing authorization medicines older than two years. These results could be very useful to develop strategiesto prevent the clinical and economic consequences of ADR (AU)

No disponible

[One-week variation of cotton dust and endotoxin levels in a cotton mill. Relation with the daily variation of the expiratory flow rates]. / Níveis de empoeiramento e endotoxinas numa fiação de algodão. Relação com a variação diária dos débitos expiratórios.

UNLABELLED: The prevalence of respiratory occupational diseases in the textile industry depends on environmental factors such cotton dust (CTD) levels and gram negative bacteria endotoxin (EDX) contamination. OBJECTIVE: To assess the environmental conditions (CTD and EDX) during one week in a cotton mill with respect to FEV1 variation throughout the work shift. POPULATION AND METHODS: 47 cotton mill workers (24F, 23M); average age: 42 +/- 11 years; average exposure to cotton dust: 22.5 +/- 9.4 years; Asthma: 15 (32%), Byssinosis: 11 (23%) and Asymptomatics: 21 (45%); a past history of respiratory symptoms: 13.1 +/- 11.7 years. Clinical evaluation, skin prick tests, a metacholine challenge, lung function tests and a work-place evaluation were performed. FEV1 Shift-variation (Delta-Shift) = end-shift FEV1 - start-shift FEV1, was calculated during one week. CTD and EDX levels were measured daily for each work place throughout this week and everyday during different operation tasks (work, cleaning, maintenance). The average values of CTD and EDX were calculated according to the time spent on each of these tasks for every worker who was exposed. RESULTS: Great variability of the environment conditions was observed throughout the week with the highest levels of CTD and EDX on Friday, even in comparison with Monday (CTD = 1.01 +/- 0.31 mg/m3 vs 0.68 +/- 0.65 mg/m3; p < 0.0005 e EDX = 33.1 +/- 8.9 ng/m3 vs 20.8 +/- 9.4 ng/m3; p < 0.0001). The shift variation was -129 +/- 97 ml for all the workers. The workers with asthma had the greatest reduction in expiratory flow rates, highest BHR and Delta-Shift but there were no differences in the levels of CTD and EDX among the three groups. Delta-Shift showed an association with the levels of EDX, specially in individuals with BHR but not with CTD levels. CONCLUSION: The environmental conditions that textile workers are exposed to, varies throughout the week and are associated with variations in flow rates and so lung function tests should be performed in a serial manner for the evaluation of respiratory occupational disease. The highest levels of EDX were recorded on Friday and this confirms the low reliability of the diagnostic criteria of byssinosis and points to the necessity of more objective measures.