Risk Factors in Severe Anaphylaxis: Which Matters the Most, Food or Cofactors?

BACKGROUND AND OBJECTIVE: The prevalence of anaphylactic shock, the most severe manifestation of anaphylaxis, remains unknown. Risk factors and biomarkers have not been fully identified. Objective: To identify risk factors in patients who experience anaphylactic shock. METHODS: Using lipid transfer protein (LTP) allergy as a model, we compared the characteristics of patients who developed anaphylaxis and anaphylactic shock. We recorded demographics, pollen sensitization, foods ingested up to 2 hours before onset of the reaction, and the presence of cofactors. Culprit foods were identified through a compatible clinical history and positive allergology work-up (skin prick test and/or sIgE). RESULTS: We evaluated 150 reactions in 55 patients with anaphylaxis (134 reactions) and 12 with anaphylactic shock (16 reactions). Patients in the anaphylaxis group experienced twice as many reactions (mean [SD], 2.4 [2.5] for anaphylaxis vs 1.3 [1.5] for anaphylactic shock; P<.02). No relationship was found between any food group and severity of the reaction. The most frequent food involved in both groups of patients was the combination of several plant-derived foods (plant food mix), followed by peach and nuts. Indeed, in the reactions caused by plant food mix, the presence of a cofactor was observed more often than in other food groups. On the other hand, cofactors were not present in peach- and nut-related reactions. Exercise was the most frequent cofactor in all groups. CONCLUSION: In our series, the severity of the reactions was not determined by the kind of food or presence of a cofactor. Anaphylactic shock seems to be an infrequent presentation that may be associated with other individual-related factors requiring further evaluation.

Internalizing and externalizing symptoms and suicidal behaviour in young people: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults. METHOD: We conducted a systematic review of articles published until January 2017. We identified 26 883 potential papers; 1701 full-text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta-analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables. RESULTS: Finally, 41 studies were included, involving participants aged 12-26 years for a systematic review, and 24 articles were included for meta-analysis. The meta-analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65). CONCLUSION: Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.

Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics.

A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between-patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food-producing animals. Nonlinear mixed effects (NLME) have been purposely designed to characterize the sources of variability in drug disposition and response. The NLME approach can be used to explore the impact of population-associated variables on the relationship between drug administration, systemic exposure, and the levels of drug residues in tissues. The latter, while different from the method used by the US Food and Drug Administration for setting official withdrawal times (WT) can also be beneficial for estimating WT of approved animal drug products when used in an extralabel manner. Finally, NLME can also prove useful to optimize dosing schedules, or to analyze sparse data collected in situations where intensive blood collection is technically challenging, as in small animal species presenting limited blood volume such as poultry and fish.

Sexual orientation and suicidal behaviour in adolescents and young adults: systematic review and meta-analysis.

BackgroundResearch suggests that lesbian, gay and bisexual (LGB) adolescents have a higher risk of suicidal behaviours than their heterosexual peers, but little is known about specific risk factors.AimsTo assess sexual orientation as a risk factor for suicidal behaviours, and to identify other risk factors among LGB adolescents and young adults.MethodA systematic search was made of six databases up to June 2015, including a grey literature search. Population-based longitudinal studies considering non-clinical populations aged 12-26 years and assessing being LGB as a risk factor for suicidal behaviour compared with being heterosexual, or evaluating risk factors for suicidal behaviour within LGB populations, were included. Random effect models were used in meta-analysis.ResultsSexual orientation was significantly associated with suicide attempts in adolescents and youths (OR = 2.26, 95% CI 1.60-3.20). Gay or bisexual men were more likely to report suicide attempts compared with heterosexual men (OR = 2.21, 95% CI 1.21-4.04). Based on two studies, a non-significant positive association was found between depression and suicide attempts in LGB groups.ConclusionsSexual orientation is associated with a higher risk of suicide attempt in young people. Further research is needed to assess completed suicide, and specific risk factors affecting the LGB population.

Exposure to violence, a risk for suicide in youths and young adults. A meta-analysis of longitudinal studies.

OBJECTIVE: To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults. METHOD: We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment [childhood physical, sexual, emotional abuse, neglect], (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population-based case-control or cohort studies; and (3) subjects aged 12-26 years. Random models were used for meta-analyses (Reg: CRD42013005775). RESULTS: From 23 682 articles, 29 articles with 143 730 subjects for meta-analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73-2.28); for child maltreatment, 2.25 (95% CI: 1.85-2.73); for bullying, 2.39 (95% CI: 1.89-3.01); for dating violence, 1.65 (95% CI: 1.40-1.94); and for community violence, 1.48 (95% CI: 1.16-1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46-25.07). CONCLUSION: Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.

rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients.

Several studies have demonstrated that matrix metalloproteinases (MMPs) play a major role in atherosclerotic plaque disruption and lead to myocardial infarction (MI). We investigated the association between the MMP1 -1607 1G/2G (rs1799750), MMP3 -1612 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms and the risk of developing MI in a Mexican mestizo cohort. The genotype analysis was performed using the restriction fragment length polymorphism-polymerase chain reaction technique in a group of 236 patients with a history of MI and 285 healthy controls. Similar distributions of rs1799750 and rs3025058 were observed in both groups; however, the MMP9 rs3918242 T allele and the CT genotype were associated with the risk of developing MI (OR = 2.32, pC = 0.02 and OR = 2.40, pC = 0.02, respectively). Multiple logistic analysis was performed between MI patients and controls to estimate the risk, and after adjusting for identified risk factors, the CT + TT genotypes of MMP9 rs3918242 were found to be significantly associated with increased risk of developing MI than those with the CC genotype (OR = 2.88, P < 0.01). In summary, our results reveal that the rs3918242 polymorphism of the MMP9 gene plays a major role in the risk of developing MI.

Understanding the pharmacokinetics of tulathromycin: a pulmonary perspective.

Tulathromycin is approved in the United States for the treatment of respiratory disease in bovine and swine, infectious bovine keratoconjunctivitis associated with Moraxella bovis, and interdigital necrobacillosis in bovine. This macrolide highly concentrates in lung tissue and persists in the intra-airway compartment for a long time after a single administration. It also accumulates in inflammatory cells, including neutrophils and macrophages. This article reviews pharmacokinetic information about tulathromycin in different veterinary species with particular emphasis on the respiratory system.

Vertical flow constructed wetlands: kinetics of nutrient and organic matter removal.

The kinetics of organic matter and nutrient removal in a pilot vertical subsurface wetland with red ferralitic soil as substrate were evaluated. The wetland (20 m(2)) was planted with Cyperus alternifolius. The domestic wastewater that was treated in the wetland had undergone a primary treatment consisting of a septic moat and a buffer tank. From the sixth week of operation, the performance of the wetland stabilized, and a significant reduction in pollutant concentration of the effluent wastewater was obtained. Also a significant increase of dissolved oxygen (5 mg/l) was obtained. The organic matter removal efficiency was greater than 85% and the nutrient removal efficiency was greater than 75% in the vertical subsurface wetland. Nitrogen and biochemical oxygen demand (BOD) removal could be described by a first-order model. The kinetic constants were 3.64 and 3.27 d(-1) for BOD and for total nitrogen, respectively. Data on the removal of phosphorus were adapted to a second-order model. The kinetic constant was 0.96 (mg/l)(-1) d(-1). The results demonstrated the potential of vertical flow constructed wetlands to clean treated domestic wastewater before discharge into the environment.

Re-descemet membrane endothelial keratoplasty (DMEK) with preservation of the original graft after free roll in anterior chamber: A case report.

INTRODUCTION: Lamellar keratoplasties have had a great impact in the management of corneal edema due to endothelial dysfunction. Minimally invasive transplant techniques such as Descemet Membrane Endothelial Keratoplasty (DMEK) have helped to reduce the morbidity involved in performing penetrating keratoplasty in this type of patient. Even so, these are complex techniques that are not free of complications and require a long line of surgical learning and an even more demanding experience in postoperative management. CLINICAL CASE: An 89-year-old woman suffering from Fuchs endothelial dystrophy and undergoing combined cataract and DMEK surgery presented stromal edema predominantly inferior and sectoral detachment of the graft 24 h after the intervention. After re-bubbling in consultations and 4 days later, the graft was observed rolled and free in the anterior chamber. She underwent re-DMEK with preservation of the original graft after 24 h, with de-epithelialization to optimize visualization. The graft was stained with trypan blue and the posterior stroma was protected with air. The graft was reimplanted under intraocular maneuvers and with an air bubble. 24 h after surgery, the adhered graft was observed, with a great decrease in stromal edema. One month later, the patient had a clear cornea, persistent complete graft adhesion, and visual acuity of 0.9. CONCLUSION: The discovery of free roll in the anterior chamber after DMEK surgery constitutes the most complex form of graft detachment. Corneal edema as well as the arrangement of the different intraocular structures are conditions to be considered for the surgical resolution of this complication. In many cases, surgical repositioning of the graft is feasible, which means saving costs without the need to use new donor corneal tissues.

How a single perioperative delirium case can make the difference.

This report describes how postoperative delirium in an elderly man during COVID-19 pandemic led to a serious event involving a central venous catheter. Delirium is a common cause of perioperative morbidity and mortality, and is characterised by an alteration in consciousness and perception and a reduced ability to focus, sustain or shift attention. The event was analysed by a multidisciplinary committee which developed a risk stratification delirium protocol in order to prevent similar events in the future.

Pharmacokinetics of macrolides in foals.

Macrolides are used for treatment of pneumonia and extrapulmonary conditions caused by Rhodococcus equi. In foals, macrolides have an extraordinary capacity to accumulate in different lung tissue compartments. These drugs show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells from foals. This article reviews the pharmacokinetic characteristics of erythromycin, azithromycin, clarithromycin, tulathromycin, telithromycin, gamithromycin, and tilmicosin in foals, with emphasis on PELF and BAL cell concentrations.

Evaluation of regional limb perfusion with erythromycin using the saphenous, cephalic, or palmar digital veins in standing horses.

There are no reported studies evaluating the use of erythromycin for regional limb perfusion (RLP) in horses. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of erythromycin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous or palmar digital (PD) vein was used to perfuse the limb with erythromycin. Synovial samples were collected from the metacarpo/metatarso-phalangeal (MCP/MTP) joint and blood samples were collected from the jugular vein. Maximum concentration (C(max)) of erythromycin in the MCP joint using the cephalic vein was 113 mg/L. The Cmax of erythromycin in the MTP joint using the saphenous vein was 38 mg/L. Erythromycin administered using the PD vein was not detectable in the MCP/MTP joint of four of six horses. Concentrations of erythromycin achieved in the synovial fluid of the MCP/MTP joint were between 152 and 452 times the minimal inhibitory concentration (MIC) for Rhodococcus equi (R. equi). In conclusion, the results indicate that when using the saphenous or cephalic veins for RLP, therapeutic concentrations of erythromycin in the MCP/MTP joint can be consistently reached [corrected].

Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses.

Previous studies have shown that regional limb perfusion (RLP) using the palmar digital (PD) vein delivers therapeutic concentration of amikacin to the distal limb. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of amikacin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous, or PD vein was used to perfuse the limb with amikacin. Two grams of amikacin was used for RLP using the saphenous and the cephalic veins, and one gram was used in the PD vein. Synovial samples were collected from the metacarpo-/metatarsophalangeal (MCP/MTP) joint, and blood samples were collected from the jugular vein. Maximum concentration (Cmax) of amikacin in the MCP/MTP joint using the cephalic and the saphenous vein was 277 and 363 mg/L, respectively. The amikacin concentrations achieved in the synovial fluid of the MCP/MTP joint in the current study were between 69 and 91 times the minimally inhibitory concentration of common susceptible bacterial pathogens causing orthopedic infections in horses. To conclude, this study shows that use of the proximal veins for RLP to treat distal limb infections is a viable alternative to using the palmar or plantar digital vein.

An acute reversible experimental model of pneumonia in pigs: time-related histological and clinical signs changes.

The objective of this study was to evaluate the long-term survival rates, clinical response, and lung gross and microscopic changes in pigs treated intratracheally with lipopolysaccharide of Escherichia coli 0111:B4 (LPS-Ec). Healthy pigs were randomly allocated to three groups: (i) no-LPS-Ec (n=1), (ii) LPS-Ec-T1 (1 mg/mL, 10 mL/pig) (n=7), and (iii) LPS-Ec-T2 (0.5 mg/mL, 10 mL/pig) (n=6). Two pigs from each dose group were euthanized at 24 (n=3 for T1), 48 and 144 h post-LPS-Ec challenge. LPS-Ec-treated animals showed macroscopic lesions in middle lobes of the lung. A reversible recruitment of macrophages and neutrophils was observed at 24, 48, and 144 h post-LPS-Ec challenge. The highest cellular infiltration level was observed at 24 h after challenge. The highest clinical scores were evident in both experimental dose levels within 3 and 5 h after LPS-Ec administration. Administration of LPS-Ec, under the conditions evaluated, can be used to induce a reproducible model of acute pulmonary inflammation in pigs.

Pulmonary pharmacokinetics of tulathromycin in swine. Part 2: Intra-airways compartments.

The objective of this study was to assess the pharmacokinetics of tulathromycin in pulmonary and bronchial epithelial lining fluid (PELF and BELF) from pigs. Clinically healthy pigs were allocated to two groups of 36 animals each. All animals were treated with tulathromycin (2.5 mg/kg/i.m). Animals in group 2 were also challenged intratracheally with lipopolysaccharide from Escherichia coli 3 h prior to tulathromycin administration. Both PELF and BELF samples were harvested using bronchoalveolar lavage fluid and bronchial micro-sampling probes, respectively. Samples were taken for 17 days post-tulathromycin administration. No statistical differences in the concentration of tulathromycin were observed in PELF between groups. The concentration vs. time profile in BELF was evaluated only in Group 1. Tulathromycin distributed rapidly and extensively into the airway compartments. The time to maximal (Tmax ) concentration was 6 h postdrug administration in PELF but 72 h post-tulathromycin administration for BELF. In group 2, the Tmax was seen at 24 h post-tulathromycin administration. The area under the concentration time curve (h*ng/mL) was 522 000, 348 000 and 1 290 000 for PELFGroup-1 , PELFGroup-2 , and BELFGroup-1 , respectively. Tulathromycin not only distributed rapidly into intra-airway compartments at relatively high concentrations but also resided in the airway lining fluid for a long time (>4 days).

Pulmonary pharmacokinetics of tulathromycin in swine. Part I: Lung homogenate in healthy pigs and pigs challenged intratracheally with lipopolysaccharide of Escherichia coli.

The objective of the study was to assess the pharmacokinetics of tulathromycin in lung tissue homogenate (LT) and plasma from healthy and lipopolysaccharide (LPS)-challenged pigs. Clinically healthy pigs were allocated to two dosing groups of 36 animals each (group 1 and 2). All animals were treated with tulathromycin (2.5 mg/kg). Animals in group 2 were also challenged intratracheally with LPS from Escherichia coli (LPS-Ec) 3 h prior to tulathromycin administration. Blood and LT samples were collected from all animals during 17-day post-tulathromycin administration. For LT, one sample from the middle (ML) and caudal lobes (CL) was taken. The concentration of tulathromycin was significantly lower in the ML after the intratracheal administration of LPS-E. coli (P < 0.02). In healthy pigs and LPS-challenged animals, the distribution of the drug into the lungs was rapid and persisted at high levels for 17-day postadministration. The distribution of the drug within the lung seems to be homogenous, at least between the middle and caudal lobes within dosing groups. The concentration versus time profile of the drug and pharmacokinetic parameters in two different lung areas (middle and caudal lobe) were consistent within the groups. The clinical significance of these findings is unknown.

Animal Health Modeling & Simulation Society: a new society promoting model-based approaches in veterinary pharmacology.

The Animal Health Modeling & Simulation Society (AHM&S) is a newly founded association (2012) that aims to promote the development, application, and dissemination of modeling and simulation techniques in the field of Veterinary Pharmacology and Toxicology. The association is co-chaired by Pr. Johan Gabrielsson (Europe), Pr. Jim Riviere (USA), and secretary Dr. Jonathan Mochel (Switzerland). This short communication aims at presenting the membership, rationale and objectives of this group.

Pharmacokinetics of tulathromycin in healthy and neutropenic mice challenged intranasally with lipopolysaccharide from Escherichia coli.

Tulathromycin represents the first member of a novel subclass of macrolides, known as triamilides, approved to treat bovine and swine respiratory disease. The objectives of the present study were to assess the concentration-versus-time profile of tulathromycin in the plasma and lung tissue of healthy and neutropenic mice challenged intranasally with lipopolysaccharide (LPS) from Escherichia coli O111:B4. BALB/c mice were randomly allocated into four groups of 40 mice each: groups T-28 (tulathromycin at 28 mg/kg of body weight), T-7, T7-LPS, and T7-LPS-CP (cyclophosphamide). Mice in group T-28 were treated with tulathromycin at 28 mg/kg subcutaneously (s.c.) (time 0 h). The rest of the mice were treated with tulathromycin at 7 mg/kg s.c. (time 0 h). Animals in dose groups T-7-LPS and T7-LPS-CP received a single dose of E. coli LPS intranasally at -7 h. Mice in group T7-LPS-CP were also rendered neutropenic with cyclophosphamide (150 mg/kg intraperitoneally) prior to the administration of tulathromycin. Blood and lung tissue samples were obtained from 5 mice from each dose group at each sampling time over 144 h after the administration of tulathromycin. There were not statistical differences in lung tissue concentrations among groups T-7, T-7-LPS, and T7-LPS-CP. For all dose groups, the distribution of tulathromycin in the lungs was rapid and persisted at relatively high levels during 6 days postadministration. The concentration-versus-time profile of tulathromycin in lung tissue was not influenced by the intranasal administration of E. coli LPS. The results suggest that in mice, neutrophils may not have a positive influence on tulathromycin accumulation in lung tissue when the drug is administered during either a neutrophilic or a neutropenic state.

Pharmacokinetics of intravenous and intramuscular tramadol in llamas.

The purpose of this study was to determine the pharmacokinetics of tramadol and its metabolite M1 after intravenous and intramuscular administration to llamas. Tramadol, a centrally acting analgesic whose efficacy is a result of complex interactions between opiate, adrenergic and serotonin receptor systems, has been used clinically to treat moderate to severe pain in humans. The pharmacokinetic parameters of tramadol and M1 in plasma were examined following intravenous and intramuscular administration to six healthy male llamas. Tramadol half-life, volume of distribution at steady-state and clearance after intravenous administration were 2.12 ± 0.37 h, 4.02 ± 1.16 L/kg and 1728.73 ± 152.82 mL/h/kg, respectively. The bioavailability was 110 ± 21% and half-life 2.54 ± 0.31 h following intramuscular administration of tramadol. M1 had a half-life of 10.40 ± 2.90 h and 7.71 ± 0.54 h following intravenous and intramuscular administration of tramadol.

The diagnostic performance of ultrasound-guided core biopsy in the diagnosis of head and neck lymphoma: results in 226 patients.

Many clinical guidelines for investigating lymphomas advise that surgical excision biopsy (SEB) should be performed for a confident diagnosis. It is increasingly recognized in clinical practice that ultrasound-guided core needle biopsy (USCNB) is a reliable diagnostic technique. We aimed to investigate the diagnostic efficacy of USCNB in head and neck lymphoma. A retrospective analysis of all diagnosed head and neck lymphomas between 2013 and 2018 was performed. Patient records, radiology and histopathology reports along with the biopsy technique: fine needle aspiration cytology (FNAC), USCNB, and SEB used were reviewed. The technique providing diagnosis and leading to initiation of treatment was identified. Two-hundred and thirty patients and 267 biopsy samples were included. A total of 226 patients underwent USCN. In 215 of 226 (95.1%) USCNB patients were fully diagnostic allowing for initiation of oncological treatment; 11 patients required a subsequent SEB to provide diagnosis. In four patients, SEB was the only investigation performed. Of the USCNB total number of procedures (number of patients n=230 is the same coincidentally as the number of USCNB procedures), 215 of 230 (93.5%) were fully diagnostic samples. In the majority of cases, USCNB provided a definitive diagnosis allowing initiation of oncological treatment, avoiding the need for SEB. USCNB should be considered the first-line diagnostic modality in appropriate cases, as it reduces time to initiate treatment, costs and avoids patients having to undergo unnecessary surgery and possible complications.