Intoxicación no intencionada por anticatarrales: medicamentos poco útiles y potencialmente tóxicos / Unintentional poisoning by cough and cold medications: Drugs with little usefulness and potential toxicity

Introducción: El uso de medicamentos para aliviar los síntomas del «resfriado común» en los niños es muy frecuente. A la falta de evidencia científica que avale su utilidad se suma la potencial toxicidad, habiéndose descrito intoxicaciones graves e incluso letales. El objetivo de este estudio es describir las características clínico-epidemiológicas de los pacientes atendidos en un servicio de urgencias pediátricas por sospecha de intoxicación no intencionada por anticatarrales. Material y métodos: Estudio analítico-observacional de los pacientes con edad inferior a 18 años atendidos en un servicio de urgencias pediátricas por sospecha de intoxicación no intencionada por un medicamento anticatarral, entre julio-2012 y junio-2020. Se clasificó la gravedad según el Poisoning Severity Score (PSS): PSS-0=sin toxicidad; PSS-1=toxicidad leve; PSS-2=moderada; PSS-3=grave; PSS-4=letal. Si la intoxicación se produjo en el transcurso de un tratamiento con el medicamento, se determinó si la edad del paciente estaba incluida en las indicaciones terapéuticas según ficha técnica. Resultados: Se recogieron 63 casos. Los medicamentos implicados fueron: anticongestivos y mucolíticos (31; 49,2%), antitusígenos (26; 41,2%), broncodilatadores orales (6; 9,5%). Se clasificaron según gravedad en: PSS-0=40 (63,5%), PSS-1=21 (33,3%), PSS-2=1 (1,6%) y PSS-3=1 (1,6%). En 29 pacientes (46%) existía antecedente de uso terapéutico; de estos, en 15 casos (51,7%) la edad del paciente era inferior a la recomendada en ficha técnica. En 14 pacientes (22,2%) la intoxicación se produjo por error en la dosis administrada por los cuidadores. Conclusión: Aunque la evidencia científica no recomienda medicamentos anticatarrales en niños, se siguen produciendo intoxicaciones no intencionadas por estos fármacos, en ocasiones moderadas o graves. (AU)

Introduction: The use of medications to relieve the symptoms of the “common cold” in children is very frequent. In addition to the lack of scientific evidence supporting its usefulness, there is evidence of potential toxicity, and serious and even fatal cases of intoxication have been described. The objective was to describe the clinical and epidemiological characteristics of the patients treated in a paediatric emergency department for suspected unintentional intoxication by a cold medicine. Material and methods: Observational and analytical study of patients aged less than 18 years managed in a paediatric emergency department for suspected unintentional poisoning by a cold medicine between July 2012 and June 2020. We classified severity according to the Poisoning Severity Score (PSS): PSS-0=no toxicity; PSS-1=mild toxicity; PSS-2=moderate; PSS-3=severe; PSS-4=lethal. If the intoxication occurred while the patient was in active treatment with the drug, we determined whether the patient's age was in the applicable range established in the therapeutic indications provided in the summary of product characteristics. Results: The study included data for 63 cases. The drugs involved were decongestants and mucolytics (31; 49.2%), antitussives (26; 41.2%) and oral bronchodilators (6; 9.5%). The distribution by severity was 40 cases with PSS-0 (63.5%), 21 with PSS-1 (33.3%), 1 with PSS-2 (1.6%) and 1 with PSS-3 (1.6%). In 29 patients (46.0%) there was a history of therapeutic use; in 15 of these cases (51.7%) the age was lower than recommended in the summary of product characteristics. In 14 patients (22.2%) the intoxication was due to administration of the wrong dose by caregivers. Conclusion: Although scientific evidence does not support the use of cold medicines in children, unintentional intoxications by these drugs keep happening, in some cases causing moderate or severe symptoms. (AU)

[Acute Drug Poisoning among Adolescents Using Over-the-counter Drugs: Current Status].

We discuss the current status of, and possible countermeasures for, acute drug poisoning among adolescents using OTC drugs. In the last 10 years, 36 patients aged <20 years who overdosed on OTC drugs were examined for the type of drug ingested, its active ingredients in cases of lethal dose intake, and the relevant place of purchase. Patients aged <20 years accounted for 30% of all the cases. The ingestion of multi-ingredient common-cold medication was the highest at 23%, and no ingestion of any first-class OTC drugs was observed. Caffeine accounted for 54% of the cases of lethal dose intake. At 80%, the most common method of drug purchase was from drugstores and other OTC vendors. In recent years, the number of adolescents patients who take lethal doses of OTC drugs has been increasing, and new measures are needed to avoid such cases. School pharmacists and vendors play a major role in reducing the incidences of drug poisoning. As drugs can be easily purchased over the counter, increasing the vendors' awareness of the problem throughout society may be the quickest way to reduce the incidences of acute drug poisoning among adolescents.

Effects of Cold-Light Bleaching on Enamel Surface and Adhesion of Streptococcus mutans.

Tooth bleaching is becoming increasingly popular among patients with tooth staining, but the safety of bleaching agents on tooth structure has been questioned. Primarily thriving on the biofilm formation on enamel surface, Streptococcus mutans has been recognized as a major cariogenic bacterial species. The present study is aimed at investigating how cold-light bleaching would change enamel roughness and adhesion of Streptococcus mutans. Human premolars were divided into 72 enamel slices and allocated into 3 groups: (1) control, (2) cold-light bleaching with 35% hydrogen peroxide (Beyond™), and (3) 35% hydrogen peroxide (Beyond™) alone. Biofilms of Streptococcus mutans were cultivated on enamel slices in 5% CO2 (v/v) at 37°C for 1 day or 3 days. Enamel surfaces and biofilms were observed using scanning electron microscope (SEM). Atomic force microscopy (AFM) was applied to quantify the roughness of enamel surface, and the amounts of biofilms were measured by optical density of scattered biofilm and confocal laser scanning microscopy (CLSM). Cold-light bleaching significantly increased (p < 0.05) surface roughness of enamel compared to controls, but significantly inhibited (p < 0.05) adhesion of Streptococcus mutans on enamel in the bacterial cultures of both 1 day and 3 days. In conclusion, cold-light bleaching could roughen enamel surface but inhibit Streptococcus mutans adhesion at the preliminary stage after the bleaching treatment.

Trends in adverse events and related health-care facility utilization from cough and cold medication exposures in children.

INTRODUCTION: Initial research following regulatory changes addressing the pediatric safety of cough and cold medications (CCMs) demonstrated decreases in adverse events (AEs). Using a national multi-source surveillance system, we studied subsequent CCM-related AE case rate trends and associated health-care facility (HCF) evaluation in children. METHODS: Data were collected from 2009 to 2016. Case eligibility included: age <12 years; exposure to an over-the-counter product containing ≥1 CCM pharmaceutical ingredient; ≥1 significant AE that occurred in the United States. RESULTS: About 4756 (72.6%) cases were determined at least potentially related to an index ingredient. Accidental unsupervised ingestions (AUIs; 3134; 65.9%) were the most common case type. Nearly half of AE cases involved children 2 to <4 years old (2,159; 45.4%). The AE case rate did not change significantly over time (p = 0.22). The proportion of AE cases resulting in HCF admission increased from 32.4% (207) in 2009 to 43.4% (238) in 2016 (p < 0.01). Exposures to diphenhydramine (1,305; 67.3%) and/or dextromethorphan (591; 30.5%) were involved in the majority of HCF admissions. CONCLUSIONS: The proportion of AE cases resulting in HCF admission increased from 2009 to 2016. Efforts to prevent AUIs such as packaging innovation and engineering controls, particularly for diphenhydramine and dextromethorphan-containing products, should be pursued.

HLA genotypes and cold medicine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications: a systematic review and meta-analysis.

Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To assess the risks of CM-induced SJS/TEN with SOC, systematic review and meta-analysis were employed. Studies investigating associations between HLA genotypes and CM-induced SJS/TEN with SOC were systematically searched in PubMed, Scopus and the Cochrane Library. Overall odds ratios (ORs) with 95% CIs were calculated using a random-effects model to determine these associations. An initial search of the databases identified 24,011 articles, of which 6 studies met the inclusion criteria. In total from all studies, associations between 81 different HLA genotypes and CM-induced SJS/TEN with SOC (i.e., 22 different HLA-A genotypes, 40 different HLA-B genotypes and 19 different HLA-C genotypes) were investigated. Risk factors to develop SJS/TEN with SOC in patients who used CM were identified from our meta-analysis. HLA-A*0206 (OR = 3.90; 95% CI = 1.96-7.77), HLA-A*3303 (OR = 2.28; 95% CI = 1.31-3.97), HLA-B*4403 (OR = 3.27; 95% CI = 1.52-7.03) and HLA-C*0501 (OR = 2.55; 95% CI = 1.19-5.44) were associated with CM-induced SJS/TEN with SOC. With our results demonstrating a significant association between using of CMs and the severe ADR, a genetic testing can be helpful. However, the CMs are commonly used as an over-the-counter drug in practically almost of people in populations worldwide, the genetic screening prior to use of the CMs might not be cost-effective. Nonetheless, for people with a family history of developing the ADRs with a possible involvement of CMs, a genetic screening may be beneficial.

Educating international students about medication access and usage in the US: A pilot project.

OBJECTIVE: To (1) describe an educational program for international students about medication access and use, (2) assess perspectives on the session Participants: A College of Pharmacy and Office of International Affairs at a large, public university presented on the U.S. pharmacy system during biannual international student orientation. Methods: During seven, 20-minute presentations, a facilitator discussed the role of pharmacists, defined terms, and reviewed processes. Anonymous, voluntary post-presentation surveys were analyzed to identify common themes. Results: An 86% response rate was achieved (n = 1496). Majority of students (98%) found this workshop helpful; a majority felt comfortable filling a prescription (96%) or asking the pharmacist a question (97%). More than 95% understood key terms. Common themes included health insurance and cost. Conclusions: This educational model equipped international students with knowledge to navigate the U.S. medication use system. Other universities may apply the program to prepare international visitors to access and safely use medications.

Robust Chromatographic Methods for the Analysis of Two Quaternary Mixtures Containing Paracetamol, Codeine, Guaifenesin and Pseudoephedrine or Phenylephrine in their Dosage Forms.

Two simple validated and highly selective methods for analysis of paracetamol, codeine, guaifenesin and pseudoephedrine or phenylephrine quaternary mixtures were developed. The first method is a high performance liquid chromatography with diode array detection method where separation was successful using Agilent C18 (150 × 4.6 mm) column, gradient elution of phosphate buffer pH 3, methanol and acetonitrile and diode-array detection at 210 nm. The second method is a HPTLC method followed by densitometric measurement of the spots at 257 nm. Separation was carried out on Merck HPTLC aluminum sheets of silica gel using methylene chloride: methanol: glacial acetic acid: ammonia (17.8: 1.68: 0.4: 0.12, v/v) mobile phase. The methods were applied successfully for analysis of both quaternary mixtures in laboratory-prepared tablets and also validated in regards to linearity, precision, accuracy, sensitivity and stability.

Development and validation of a generic RP-HPLC PDA method for the simultaneous separation and quantification of active ingredients in cold and cough medicines.

A novel generic reverse phase high performance liquid chromatography (RP-HPLC) method is developed and validated for simultaneous determination of seven pharmaceutically active ingredients, namely, acetaminophen, dextromethorphan, doxylamine, phenylephrine, guaifenesin, caffeine and aspirin. All seven ingredients were quantified in soft gel, syrup and tablet formulations of the over-the-counter US-marketed products, as per the guidelines of the International Conference on Harmonization. The separation was achieved in a 16 min run time on an Agilent Zorbax Phenyl column using a gradient method with two mobile phases. Mobile phase A was 0.15% trifluoro acetic acid in purified water and while mobile phase B was a mixture of acetonitrile and methanol (750:250 v/v) with 0.02% trifluoro acetic acid. The flow rate was 1.0 mL min-1 and injection volume was 10 µL. Detection was performed at 280 nm using a photodiode array detector. As part of the method validation, specificity, linearity, precision and recovery parameters were verified. The concentration and area relationships were linear (R2 > 0.999), over the concentration ranges 20-120 µg mL-1 for acetaminophen, 75-450 µg mL-1 for dextromethorphan, 31.25-187.5 µg mL-1 for doxylamine, 25-150 µg mL-1 for phenylephrine, 25-150 µg mL-1 for aspirin, 6.5-39 µg mL-1 for caffeine and 12-72 µg mL-1 for guaifenesin. The relative standard deviations for precision and intermediate precision were <1.5%. The proposed RP-HPLC generic method is applicable for routine analysis of cold and cough over-the-counter products.

Non-prescription cold and flu medication-induced transient myopia with uveal effusion: case report.

BACKGROUND: To report a case of non-prescription cold and flu medication-induced transient myopia with uveal effusion. CASE PRESENTATION: Bilateral high intraocular pressure, shallow anterior chambers, uveal effusion, and a myopic shift were encountered in a 39-year-old Chinese male 1 night after taking a non-prescription flu medicine three times than the recommended dose. Ultrasound biomicroscopy (UBM) showed bilateral ciliochoroidal effusions, disappearance of the ciliary sulcus, closure of the angle of the anterior chamber, and anterior displacement of the lens-iris diaphragm. Treatment with aqueous suppressants was given. Within a week, the uncorrected vision restored, and the myopia had disappeared. UBM revealed major resolution of the ciliochoroidal effusions in both eyes, deepening of the anterior chamber, return of the lens-iris diaphragm to a more posterior position. CONCLUSIONS: Overdose of non-prescription cold and flu medication may cause bilateral uveal effusions inducing acute angle-closure glaucoma and acute myopia.

Availability of drug at convenient stores is not associated with an increased incidence of their poisoning.

PURPOSE: In late 2012, South Korea revised the Pharmaceutical Affairs Act to make selected medications including acetaminophen, ibuprofen, and cold medications available in nonpharmacy outlets, including the 24-hour convenient stores (CVS). The objective of this study was to identify whether the characteristics and trend of self-poisonings associated with these medications were altered after the legislative change. METHODS: A retrospective study was performed using national data from the Emergency Department (ED)-based Injury In-depth Surveillance database. The patients diagnosed with poisoning were sorted from 2011 to 2016 and included in the study. As the Act was implemented from 2013, the demographic characteristics and clinical outcomes were compared before and after January 2013. A piecewise regression analysis was performed to determine the association between the monthly use of acetaminophen, medication for cold, and nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of total poisonings before and after the January 2013. RESULTS: Among 1 536 277 patients included in the database, 17 523 patients diagnosed with poisoning were enrolled. After the legislative change, the etiology of poisoning did not change, although the frequency of hospitalization from ED was significantly increased. The monthly trend for poisoning due to acetaminophen, cold medications, and NSAIDs showed no significant slope change between before and after the legislative change. The proportional use of acetaminophen and cold medications was significantly decreased, while that of NSAIDs was unchanged before and after the legislative change. CONCLUSIONS: The change in the Pharmaceutical Affairs Act was not associated with any change in the monthly frequency of medication-related poisoning.

Baloxavir marboxil: un potente inhibidor de la endonucleasa cap-dependiente de los virus gripales / Baloxavir marboxil: a potent cap-dependent endonuclease inhibitor of influenza viruses

Baloxavir marboxil (ácido 5-hidroxi-4-piridona-3-carboxilo) es un nuevo fármaco antiviral con especial eficacia sobre los virus gripales que actúa inhibiendo la endonuclease cap-dependiente que precisan para su replicación. Es el primer representante de los denominados inhibidores de la proteína básica 2 (PB2) gripal. Ha mostrado eficacia frente a los virus gripales A y B y la mayoría de cepas de origen animal (gripe aviar). Los ensayos clínicos realizados en pacientes sanos de entre 12 y 64 años sin patologías y no hospitalizados (gripe leve) han mostrado una reducción de la duración de la sintomatología parecida a la obtenida por oseltamivir. Sin embargo baloxavir es un inhibidor de la replicación viral mucho más potente que este fármaco. Se ha mostrado como un fármaco seguro y bien tolerado. Se administra una sola dosis de 40-80 mg las primeras 48 horas del inicio de los síntomas. En estos ensayos se han detectado cepas con sensibilidad moderada (mutantes PA/I38T) en el 2,2% de la gripe A (H1N1)pdm09 y en el 9,7% de la gripe A (H3N2). A pesar de estos datos podría ser un buen fármaco para tratar la gripe leve o moderada, precisando de ensayos en gripe grave y pacientes con patologías crónicas para establecer su verdadera utilidad clínica

Baloxavir marboxil (5-hydroxy-4-pyridone-3-carboxyl acid) is a new antiviral drug with special efficacy on influenza viruses that acts by inhibiting the cap-dependent endonuclease required for its replication. It is the first representative of the so-called inhibitors of influenza-like PB2. It has shown efficacy against influenza viruses A and B and most strains of animal origin (avian flu). Clinical trials conducted in healthy patients between 12 and 64 years without pathologies and not hospitalized (mild flu) have shown a reduction in the duration of symptoms similar to that obtained by oseltamivir. However, baloxavir is a much more potent inhibitor of viral replication than this drug. It has been shown as a safe and well tolerated drug. A single dose of 40-80 mg is administered the first 48 hours after onset of symptoms. In these trials, strains with moderate sensitivity (PA / I38T mutants) were detected in 2.2% of influenza A (H1N1) pdm09 and in 9.7% of influenza A (H3N2). Although these data could be a good drug to treat mild or moderate influenza, requiring trials in severe influenza and patients with chronic diseases to establish their true clinical utility

Over-the-Counter Medicines and Diabetes Care.

OBJECTIVES: People with diabetes turn to over-the-counter (OTC) medicines for many ailments. The focus of this brief review is the impact common OTC medicines might have on this group of patients. METHODS: Three types of OTC medicines were selected as most deserving of attention: 3 herbal agents, nonsteroidal anti-inflammatory drugs (NSAIDs) and cough/cold products. Existing literature was used to determine precautions that might be in order. RESULTS: Herbal/natural agents with the potential to impact blood sugar have been identified in various reports. In discussing 3, glucosamine and cinnamon (at doses recommended on commercial products) should have minimal impact on diabetic management, whereas St. John's wort is a concern involving potential drug interactions. For colds, of about 11 active ingredients, only decongestants (primarily oral) need be considered for their possible effects on blood sugar. Finally, NSAIDs (even at OTC doses) must be used with caution, given their cardiovascular, renal and gastrointestinal risks. Care guidelines do encourage patients to take ownership of their condition. Yet the ability to self-medicate safely is not a certainty. In spite of easy access and a reasonable level of safety, OTC medicines still can negatively impact a user. NSAIDs available without prescription continue to cause concern. CONCLUSIONS: Before the use of any medicine, a person must ensure it will be safe. A health-care provider can be asked for assistance, but that option may not always be employed. Package information is there to provide critical information in lieu of that, something the self-medicating patient will, it is hoped, embrace.

General practice consultations and use of prescription drugs after changes to school absence policy. / Legesøkning og legemiddeluttak etter innføring av nye fraværsregler.

BACKGROUND: New rules for absence with stricter requirements for documentation were introduced in upper secondary schools in the autumn of 2016. We investigated the use of general practice services and dispensing of prescription drugs among 16 ­ 18-year-olds in the autumn of 2016 and compared this with equivalent figures for the period 2013 ­ 15. MATERIAL AND METHOD: We retrieved information on consultations in general practice (GP) and dispensing of prescription drugs to 15 ­ 18-year-olds in the period 2013 ­ 16 from the Directorate of Health's system for control and payment of health reimbursements (KUHR) and the Norwegian Prescription Database respectively. The number of consultations and dispensing of drugs were compared to previous years using Poisson regression (reference year 2015). The incidence rate ratio (IRR) was used as an outcome measure. RESULTS: The number of GP consultations for 16 ­ 18-year-olds was 30 % higher in the autumn of 2016 than in the autumn of 2015 (IRR 1.30, 95 % confidence interval (CI) 1.29 ­ 1.31). In the same period, the dispensing of drugs to this age group increased by 8 % (IRR 1.08, 95 % CI 1.08 ­ 1.09). Among the diagnosis groups, respiratory tract infections had the largest increase (IRR 2.21, 95 % CI 2.17 ­ 2.25). The largest increase in drug dispensing was found for remedies for coughs and colds (IRR 1.73, 95 % CI 1.65 ­ 1.80). INTERPRETATION: The increase in consultations in general practice and dispensing of drugs to 16 ­ 18-year-olds coincided in time with the introduction of new rules for absence from school. We hold it to be highly likely that the changes were caused by the stricter rules for documentation of absence from school.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Safety Profile of Cough and Cold Medication Use in Pediatrics.

BACKGROUND AND OBJECTIVES: The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. METHODS: Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources. An expert panel determined relatedness, dose, intent, and risk factors. Case characteristics and AEs are described. RESULTS: Of the 4202 cases reviewed, 3251 (77.4%) were determined to be at least potentially related to a CCM, with accidental unsupervised ingestions (67.1%) and medication errors (13.0%) the most common exposure types. Liquid (67.3%), pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children <2 years of age (70.0%) and none involved a therapeutic dose. The overall reported AE rate was 0.573 cases per 1 million units (ie, tablets, gelatin capsules, or liquid equivalent) sold (95% confidence interval, 0.553-0.593) or 1 case per 1.75 million units. CONCLUSIONS: The rate of AEs associated with CCMs in children was low. Fatalities occurred even less frequently. No fatality involved a therapeutic dose. Accidental unsupervised ingestions were the most common exposure types and single-ingredient, pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts.

Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population.

Importance: Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). Objective: To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs. Design, Setting, and Participants: This case-control study was conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014. Main Outcomes and Measures: Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes. Results: Of 74 patients included in the analysis, 32 (43%) were male; mean (SD) age was 36.01 [15.42] years. HLA-A*66:01 (odds ratio [OR], 24.0; 95% CI, 2.79-206.0; P < .001), HLA-B*44:03 (OR, 2.71; 95% CI, 1.11-6.65; P = .04), and HLA-C*12:03 (OR, 5.6; 95% CI, 1.67-18.80; P = .006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11:01 (OR, 0.074; 95% CI, 0.004-1.26; P = .008), HLA-B*08:01 (OR, 0.15; 95% CI, 0.02-1.15; P = .048), and HLA-B*51:01 (OR, 0.23; 95% CI, 0.05-1.03; P = .045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry; 14 males and 25 females; age, 35.2 [14.4] years; and 133 controls: 66 Pardo and 61 European ancestry; 55 males and 78 females; age, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66:01 and HLA-C*12:03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66:01 was associated with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 12.2; 95% CI, 1.19-125.0; P = .03; and European: OR, 21.2; 95% CI, 0.97-465.0; P = .04). An association was observed only in the European cohort for HLA-B*44:03 (OR, 5.50; 95% CI, 1.47-20.50; P = .01) and HLA-C*12:03 (OR, 8.79; 95% CI, 1.83-42.20; P = .008). Conclusions and Relevance: This study suggests that HLA-A*66:01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44:03 and HLA-C*12:03 might be markers only in those of European ancestry. Moreover, HLA-A*11:01 might be a marker of resistance to CM-SJS/TEN with SOCs.

Mioclonías secundarias a fármaco antigripal / Myoclonus secondary to use of anti-flu drug

No disponible

Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens-Johnson syndrome with severe ocular complications.

A genome-wide association study (GWAS) for cold medicine-related Stevens-Johnson syndrome (CM-SJS) with severe ocular complications (SOC) was performed in a Japanese population. A recently developed ethnicity-specific array with genome-wide imputation that was based on the whole-genome sequences of 1070 unrelated Japanese individuals was used. Validation analysis with additional samples from Japanese individuals and replication analysis using samples from Korean individuals identified two new susceptibility loci on chromosomes 15 and 16. This study might suggest the usefulness of GWAS using the ethnicity-specific array and genome-wide imputation based on large-scale whole-genome sequences. Our findings contribute to the understanding of genetic predisposition to CM-SJS with SOC.

Tratamiento antigripal: fármacos actualmente utilizados y nuevos agentes en desarrollo / Anti-influenza treatment: drugs currently used and under development

La gripe es una enfermedad contagiosa altamente prevalente y con significativa morbimortalidad. El tratamiento disponible con fármacos antivirales, de ser administrado de forma precoz, puede reducir el riesgo de complicaciones severas; sin embargo, muchos tipos de virus desarrollan resistencia a estos fármacos, reduciendo notablemente su efectividad. Ha habido un gran interés en el desarrollo de nuevas opciones terapéuticas para combatir la enfermedad. Una gran variedad de fármacos han demostrado tener actividad antiinfluenza, pero aún no están disponibles para su uso en la clínica. Muchos de ellos tienen como objetivo componentes del virus, mientras que otros son dirigidos a elementos de la célula huésped que participan en el ciclo viral. Modular los componentes del huésped es una estrategia que minimiza el desarrollo de cepas resistentes, dado que estos no están sujetos a la variabilidad genética que tiene el virus. Por otro lado, la principal desventaja es que existe un mayor riesgo de efectos secundarios asociados al tratamiento. El objetivo de la presente revisión es describir los principales agentes farmacológicos disponibles en la actualidad, así como los nuevos fármacos en estudio con potencial beneficio en el tratamiento de la gripe

Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza