High Rate Of Adverse Reactions Research Articles

Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer.

Most patients with differentiated thyroid cancer have a good prognosis afterradioactive iodine-131 treatment, but there are still a small number of patients who are not sensitive to radioiodine treatment and may subsequently show disease progression. Therefore, radioactive-iodine refractory differentiated thyroid cancer treated with radioiodine usually shows reduced radioiodine uptake. Thus, when sodium iodine symporter expression, basolateral membrane localization and recycling degradation are abnormal, radioactive-iodine refractory differentiated thyroid cancer may occur. In recent years, with the deepening of research into the pathogenesis of this disease, an increasing number of molecules have become or are expected to become therapeutic targets. The application of corresponding inhibitors or combined treatment regimens for different molecular targets may be effective for patients with advanced radioactive-iodine refractory differentiated thyroid cancer. Currently, some targeted drugs that can improve the progression-free survival of patients with radioactive-iodine refractory differentiated thyroid cancer, such as sorafenib and lenvatinib, have been approved by the FDA for the treatment of radioactive-iodine refractory differentiated thyroid cancer. However, due to the adverse reactions and drug resistance caused by some targeted drugs, their application is limited. In response to targeted drug resistance and high rates of adverse reactions, research into new treatment combinations is being carried out; in addition to kinase inhibitor therapy, gene therapy and rutin-assisted iodine-131 therapy for radioactive-iodine refractory thyroid cancer have also made some progress. Thus, this article mainly focuses on sodium iodide symporter changes leading to the main molecular mechanisms in radioactive-iodine refractory differentiated thyroid cancer, some targeted drug resistance mechanisms and promising new treatments.

Ultrasound-Guided Femoral Nerve Block in Geriatric Patients with Hip Fracture in the Emergency Department.

Background and Objectives: Systemic analgesics, including opioids, are commonly used for acute pain control in traumatic hip fracture patients in the emergency department (ED). However, their use is associated with high rates of adverse reactions in the geriatric population. As such, the aim of this study was to investigate the impact of lidocaine-based single-shot ultrasound-guided femoral nerve block (USFNB) on the standard care for acute pain management in geriatric patients with traumatic hip fracture in the ED. Methods: This retrospective, single-center, observational study included adult patients aged ≥60 years presenting with acute traumatic hip fracture in the ED between 1 January 2017 and 31 December 2020. The primary outcome measure was the difference in the amount of opioid use, in terms of morphine milligram equivalents (MME), between lidocaine-based single-shot USFNB and standard care groups. The obtained data were evaluated through a time-to-event analysis (time to meaningful pain relief), a time course analysis, and a multivariable analysis. Results: Overall, 607 adult patients (USFNB group, 66; standard care group, 541) were included in the study. The patients in the USFNB group required 80% less MME than those in the standard care group (0.52 ± 1.47 vs. 2.57 ± 2.53, p < 0.001). The multivariable Cox proportional hazards regression models showed that patients who received USFNB achieved meaningful pain relief 2.37-fold faster (hazard ratio (HR) = 2.37, 95% confidence intervals (CI) = 1.73–3.24, p < 0.001). Conclusions: In geriatric patients with hip fractures, a lidocaine-based single-shot USFNB can significantly reduce opioid consumption and provide more rapid and effective pain reduction.

Efficacy of erythromycin compared to clarithromycin and azithromycin in adults or adolescents with community-acquired pneumonia: A Systematic Review and meta-analysis of randomized controlled trials

BackgroundIt is debatable whether erythromycin has similar efficacy to other macrolides in treating community-acquired pneumonia (CAP). The aim of this meta-analysis is to compare the efficacy of erythromycin with clarithromycin and azithromycin. MethodsWe performed this meta-analysis of randomized controlled trials (RCTs) of adults or adolescents with CAP which compared the efficacy of erythromycin monotherapy to either azithromycin or clarithromycin. We searched PubMed and EMBASE and Cochrane Library databases and three clinical trial registries up to November 02, 2021. We evaluated heterogeneity and used random-effects models to perform risk ratios with 95% confidence intervals. ResultsWe included four RCTs (total of 472 patients), which compared the clinical efficacy of erythromycin versus clarithromycin. No studies comparing monotherapy of erythromycin versus azithromycin were found. Erythromycin use was associated with significantly lower rates of clinical success (RR, 0.79; 95% CI, 0.64 to 0.98; P-value = 0.033; I2 = 20.27%), clinical cure (RR,0.67; 95% CI, 0.48 to 0.92; P-value = 0.014; I2 = 8.75%), and radiological success (RR, 0.84; 95% CI, 0.71 to 0.996; P-value = 0.045; I2 = 20.12%) than clarithromycin. ConclusionErythromycin is less effective than clarithromycin as empiric treatment of CAP in adults and adolescents. Because of this and the higher rate of adverse reactions, erythromycin should not be used in the majority of CAP patients when azithromycin and clarithromycin are available.

Immunosupression in IgA Nephropathy

IgA Nephropathy (IgAN) is one of the most frequent types of glomerulonephritis encountered in adults from Western countries and Asia. IgAN is responsible for approximately 40% of end-stage renal disease (ESRD) mediated by glomerular impairment. The majority of adult IgAN patients present a slowly progressive pattern towards ESRD. Current types of treatment are based mainly on supportive care: i.e., life style risk factors, measures that lower blood pressure and reduce proteinuria, weight loss, smoking cessation or glycaemia control. Because IgAN is an immune complex-mediated disease, immunosuppression therapy gains more and more attention as a modality of treatment. Despite the beneficial effects, the value of immunosuppression remains controversial due to high rates of adverse reactions. The aim of this review is to highlight the benefits and limitations of promoting immunosuppression in IgAN with mild to moderate proteinuria despite supportive antiproteinuric therapy up titrated to maximum tolerated doses.

The Effects of Axitinib plus Tislelizumab in the Treatment of Advanced Renal Cell Carcinoma.

Objective To study and analyze the clinical efficacy of axitinib combined with tislelizumab in the treatment of advanced renal cell carcinoma and its effects on renal function and serum cytokines. Methods Totally 49 patients with advanced renal cancer treated in our hospital from November 2018 to January 2020 were randomized to treatment with axitinib (control group, n = 27) or axitinib combined with tislelizumab (study group, n = 22). The clinical efficacy, renal function and adverse reactions were compared between the two groups. Results After treatment, both groups showed a significant decrease in blood urea nitrogen (BUN) and serum creatinine (SCR), but treatment with axitinib plus tislelizumab led to a significantly greater reduction than did the axitinib (each p < 0.05). After treatment, both groups showed a significant decrease in TNF-β1, VEGF, TIMP-1, and MMP-2, but treatment with axitinib plus tislelizumab led to a significantly greater reduction than did the axitinib (each p < 0.05). The study group had significantly higher rates of adverse reactions (p < 0.05). Significant difference was observed in ORR (59.1% vs 40.7%) and DCR (81.8% vs 66.7%) between the study group and the control group, with higher results in study group (p < 0.05). The study group was superior to the control group in OS (p < 0.05). Conclusion Our study presents an effective alternative for advanced renal cell carcinoma by using axitinib plus tislelizumab. Limitations merit attention, and the study group had higher rates of adverse reactions. Therefore, further studies are suggested to secure a larger population of subjects.

Analysis of efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis

ObjectivesThe study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. MethodsThe randomized controlled study included 50 Mycobacterium tuberculosis culture or pathological-confirmed multidrug resistant tuberculosis patients who received spinal surgery from January 2018 to February 2020. Twenty-five patients were assigned to the control group and the study group, respectively. Random number method was used for patient allocation and they were treated with levofloxacin, pyrazinamide, thioisonicotinamide enteric-coated tablet, amikacin sulfate injection, and sodium p-amino salicylate injection, accompanied by linezolid or not. ResultsThe overall effective rate of the study group was higher than that of the control group (88.00% vs 64.00%, P<0.05). The severity of pain at 3 and 6 months postoperatively was lower in the study group than that in the control group (P<0.05). Postoperatively, the study group had higher bone graft fusion rate, shorter mean bone graft fusion time, and higher paraspinal cyst absorption rate than the control group (P<0.05). Postoperatively, the study group had lower levels of PCT, ESR, and CRP than the control group (P <0.05). All patients had normal hepatic and renal function, and no statistical difference of adverse effects between 2 groups were found. ConclusionsLinezolid-based chemotherapeutic regimens can effectively treat patients with postoperative multidrug-resistant spinal tuberculosis but have higher rates of adverse reactions.

Efficacy of Phloroglucinol Tamsulosin Combination Therapy for Medical Expulsion of Lower Ureteral Calculi and Influence on Patients’ Cys-C Level

Objective: Phloroglucinol is a myotropic, non-atropine and non-papaverine smooth muscle antispasmodic which directly acts on the smooth muscles of the gastrointestinal tract and the urogenital tract with no anticholinergic effect, no symptoms like xerostomia, visual impairment, dysuria, hypotension, increased heart rate, and arrhythmia etc. To investigate the efficacy of phloroglucinol tamsulosin combination therapy for medical expulsion of lower ureteral calculi and influence on patients’ Cys-C level. Methods: Equally randomized 136 patients with lower ureteral calculi in our hospital into mono therapy group (phloroglucinol alone) and combination therapy group (additional tamsulosin was advised). The expulsion rate, expulsion time, stone diameter and levels of IL-10, CRP, NGAL, Cys-C, KIM-1 were compared between two groups, also with the effectiveness and the rate of adverse reactions. Results: The combination therapy group showed higher expulsion rate (P&lt;0.05) and shorter expulsion time (P&lt;0.05) than that of the mono therapy group and the stone diameter was slightly larger as well (P&lt;0.05). Also, patients under combination treatment had elevated IL-10, CRP, NGAL, Cys-C and KIM-1 levels and a better overall response rate (P&lt;0.05) while it was associated with a slightly higher rate of adverse reactions (P&gt;0.05). Conclusions: Phloroglucinol tamsulosin combination therapy had clear advantages on medical expulsion of lower ureteral calculi in respect of higher expulsion rate and elevated IL-10, CRP, NGAL, Cys-C and KIM-1 levels with larger stone diameter in a shorter time.

235. Outcomes Associated with Extended Oral Antibiotic Prophylaxis After 2-Stage Exchange Surgery to Prevent Recurrent Prosthetic Joint Infection

Background2-stage exchange (2SE) surgery is often used to treat chronic prosthetic joint infections (PJI). IDSA guidelines do not recommend oral antibiotic suppression after 2SE. However, a recent randomized trial suggested that oral antibiotics for 3 months after arthroplasty reimplantation may prevent recurrent PJI. Objective: To compare rates of treatment failure (i.e., recurrent PJI) and adverse reactions (ARs) among patients who received < 1 month of antibiotics directly after reimplantation to those who received 1-3 months of antibiotics following reimplantation (extended antibiotics). MethodsThis retrospective cohort study included patients with hip, knee, or shoulder PJI who underwent 2SE at 83 VA hospitals between the years 2003-2017. PJI was defined using administrative codes and microbiology data. Patients were followed for 5 years to assess treatment failure (TF) and ARs. TF was defined as recurrent PJI, debridement, or reoperation. ARs included Clostridioides difficile infections (CDI), or antibiotic associated diarrhea (AAD) during or 72 hours after antibiotics. Chi-square tests were used to compare outcomes. Cumulative incidence function curves were created to compare TF rates between those who did and did not receive extended antibiotic treatment, incorporating the competing risks of TF and death.ResultsOf the 433 patients, most (97%) received < 1 month of oral antibiotics and 3% received extended antibiotics. The 15 patients who received extended antibiotics had similar rates of TF and ARs compared with patients who received < 1 month of oral antibiotics (Table). However, there was a trend toward higher rates of CDI (6.7% vs. 3.8%) and AAD (13.3% vs. 9.6%) among those who received extended antibiotics. There was no difference in TF comparing extended antibiotics with < 1 month of antibiotics, accounting for death (Figure). Table: Treatment Failure and Adverse Reactions Among Those Who Did and Did Not Receive Extended Antibiotics ConclusionFew patients received extended oral antibiotics in the study period. There were no statistically significant differences in TF or ARs between the 2 groups. Yet, there was a trend toward higher rates of ARs among the extended antibiotic group. Future prospective studies should assess both the potential benefits and ARs associated with extended antibiotics among patients undergoing 2SE surgery.Disclosures Marin L. Schweizer, PhD, 3M (Grant/Research Support)PDI (Grant/Research Support) Bruce Alexander, PharmD, Bruce Alexander Consulting (Independent Contractor) Daniel Suh, MS MPH, General Electric (Shareholder)Merck (Shareholder)Moderna (Shareholder)Smile Direct Club (Shareholder) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing) Andrew Pugely, MD, MBA, Globus Medical (Research Grant or Support)Medtronic (Consultant)United Healthcare (Consultant)

Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial

Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P= .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P= .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Cost-effectiveness of agents used for evaluation of ureteral patency during intraoperative cystoscopy in gynecologic and urogynecologic surgery

Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents. To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties. Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes. Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.

Safety of COVID-19 vaccination in patients with mastocytosis and monoclonal mast cell activation syndrome

Safety of COVID-19 vaccination in patients with mastocytosis and monoclonal mast cell activation syndrome

Biologic therapy for food allergy.

With the rising prevalence, food allergies have become a significant health burden that affects 6% to 13% of the global population. Although oral immunotherapy (OIT) has been promising for food allergies, this therapy has limitations, including high rates of adverse reactions and long treatment periods. Biologics may address these limitations by increasing the safety and tolerability of OIT and decreasing treatment periods. The use of biologics and vaccines are actively being explored as monotherapy as well as adjunctive therapy in combination with allergen specific OIT. A number of biologics that target key molecules known to be involved in food allergy are under investigation, including anti-immunoglobulin E therapy (omalizumab), anti-interleukin (IL) 4 receptor a (dupilumab), anti-IL-5 (mepolizumab and reslizumab), and anti-IL-5R (benralizumab), anti-IL-33 (etokimab), and peanut DNA plasmid vaccines. In the era of precision medicine, the future of food allergy looks promising, and biologics will provide treatment as well as further insights into the molecular mechanisms associated with food allergy.

Efficacy and Safety of First-Line Therapeutic Drugs with Potential for the Treatment of Novel Coronavirus Pneumonia: A Meta-Analysis

Background: Novel coronavirus pneumonia is spreading all over the world. While countries are actively dealing with the epidemic situation, the lack of specific drugs also indirectly makes the situation hard to control. At present, the internationally controversial first-line treatment drugs cover Hydroxychloroquine, Favipiravir, Remdesivir and so on. Methods: To evaluate the efficacy and safety of first-line treatment drugs for novel coronavirus pneumonia, this study investigated the turning-negative rate in the viral nucleic acid, survival rate and adverse reactions rate of novel coronavirus pneumonia patients under treated with Hydroxychloroquine, Azithromycin, Favipiravir and Remdesivir by performing meta-analysis. Findings: The result showed that hydroxychloroquine could not improve the turning-negative rate in the viral nucleic acid detection of novel coronavirus pneumonia patients compared with conventional therapy (RR=0·925, 95% CI (0·685, 1·250), P=0·61), and at the same time, it also associated with high adverse reactions rate up to 21·6%. Hydroxychloroquine combined with azithromycin can significantly increase the turning-negative rate to almost 62%, but patients’ survival rate is reduced for serious adverse reaction. The efficacy of favipiravir is stable (RR=2·70, 95% CI (1·25, 5·85), P=0·012) and its adverse reaction is under control (ES=6·10%, 95% CI (0·000, 0·121)). Remdesivir shows its therapeutic potential, but the high rate of adverse reactions (ES=58·20%, 95% CI (0·316, 0·848)) is also worthy of attention. More high-quality clinical trial data is required to investigate the efficacy and safety of first-line treatment drugs in further research. Interpretation: In summary, this article found that the clinical medication regimen for patients with mild and common COVID-19 is hydroxychloroquine 400mg/day or favipiravir 1200mg/day, and could be appropriately combined with conventional treatment, such as oxygen theraphy and carrimyclin, abidol, etc. For patients with severe COVID-19, daily use of remdesivir 100~200mg has the best effect, the treatment of hydroxychloroquine combined with azithromycin is regarded as the a last resort because of its severe adverse reaction and it can be combined with oxygen therapy together with other antibacterial drugs. And we suggest FDA to approve the favipiravir to use for patients and decrease the use of hydroxychloroquine combined with azithromycin. Funding Statement: This research work was supported by the National Natural Science Foundation of China (Grant No. 81973180 and No. 81673298), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China for Excellent Young Talents (Grant No. BK20180077) and the Drug Innovation Major Project (2019ZX09301-142.) Declaration of Interests: The authors declare no competing interests.

A scoping review and network meta-analysis for efficacy and safety of glaucoma medication in Japanese patients.

To investigate the efficacy and safety of glaucoma medication in Japanese patients, network meta-analysis (NMA) of an intraocular pressure(IOP) reduction, adverse reaction rates and conjunctival congestion rates of major glaucoma drugs used in clinical practice in Japan were conducted using the new drug application (NDA) data. Scoping network meta-analysis. Out of all clinical trials in the interview forms of major glaucoma drugs approved in Japan as of July 2015, active-control clinical trials with Japanese patients were identified through screening with specific criteria. The details of IOP reduction, adverse reaction rates and conjunctival hyperemia rates of the trials were collected from published articles, package inserts, interview forms and Summary basis of approval made by Japan Pharmaceutical and Medical Devices Agency (PMDA). The mean difference in IOP reduction, adverse reaction rates, and conjunctival hyperemia rates of eligible trials were assessed using NMA as referenced to those of timolol maleate 0.5%. Eleven multicenter trials of ten medications in total, (five prostaglandin (PG) analogs, three β-blockers, one α-1 blocker, and one α-2 stimulator) were selected. The mean difference in IOP reduction in mmHg with 95% confidence intervals were as follows: bimatoprost -3.00 (-3.71; -2.29), tafluprost -2.45 (-3.65; -1.25), travoprost -2.35 (-3.41; -1.29), and latanoprost -2.05 (-2.72; -1.38). The highest IOP reduction was achieved by PG analogs. Adverse reaction rates and conjunctival hyperemia rates were significantly larger with PG analogs than with other medications. The efficacy and safety of glaucoma medications were assessed by NMA as reference to those of timolol maleate 0.5% in Japanese patients. PG analogs were the most efficacious in reducing IOP. However, PG analogs were also associated with higher rates of adverse reactions and conjunctival hyperemia.

Can food allergy be cured? What are the future prospects?

Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6%-13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine autoinjectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food-allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen-specific immunotherapy, vaccines, and non-allergen-specific therapies (eg, monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres

ObjectivesChagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole. MethodsThis was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)). Results471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08). ConclusionThe use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.

Sex differences in rate and rhythm control for atrial fibrillation.

Atrial fibrillation (AF), is the most common sustained arrhythmia and is associated with a substantial increase in morbidity and mortality. Several studies have demonstrated sex-related differences in various aspects, including age at diagnosis, clinical manifestations, management and prognosis. These dissimilarities may dictate different approaches to management and could translate to differences in outcomes. However, similarly to other cardiovascular therapies, there may be a tendency to treat females more conservatively and less aggressively than male patients. The use of oral anticoagulants, for example, is lower in female patients with AF. Electrical cardioversion is less often used. Likewise, despite higher rates of adverse reactions to antiarrhythmic drugs in women, they are less likely to undergo catheter ablations, a well-established therapeutic approach to symptomatic patients with recurrences of AF. In this article, we review sex related dissimilarities in patients with AF. In addition, we discuss various treatment options, and specifically refer to differences in access of treatment, success rates, and potential treatment-related complications.

Profile of blood donors who presented adverse reactions to the donation.

identify the adverse reactions presented by blood donors and outline their sociodemographic profile. a quantitative, cross-sectional retrospective study of 780 records of blood donors from a public hemocenter in the southern region of Brazil, from December 2015 to January 2016. For the analysis the descriptive statistics was used. it was identified that throughout 12 months, the total blood donors corresponded to 27,300 people, in which 780 developed at least one reaction. They were characterized by female and recurrent donors, single, with a complete average level of education, ranging from 16 to 30 years, who triggered between 1 and 3 reactions. Mild reactions were more frequent, followed by moderate and severe reactions. There is a high rate of adverse reactions from donors emphasizing the need for changes in hemotherapy care practices.

Estimation of Transport and Kinetic Parameters of a Solid-State Lithium Battery

Research on solid-state batteries began in the 1950s to address issues that stem from the liquid electrolyte, such as electrolyte leakage. Today, with implementation of batteries in larger systems like electric vehicles or the grid, the performance demands are greatly increased, which compounds the safety issues associated with electrolyte decomposition. In solid state batteries, a solid electrolyte is utilized, which eliminates the use of flammable, organic solvents in the cell. Solid state electrolytes transport ions with better selectivity than liquid electrolytes, which reduces unwanted side reactions. Liquid electrolyte decomposition can also accelerate passivation of the solid/electrolyte interface1. Solid-state batteries may be the key to the development of safe lithium batteries. Lithium batteries are exciting next generation energy storage as lithium anodes have the most negative potential of any known material, which enables lithium anodes to have a high energy density and high discharge voltage. However, lithium batteries suffer from many issues that have prevented their widespread commercialization as rechargeable cells. When lithium metal batteries are cycled, the anode is used non-uniformly which leads to the development of finger-like dendrites. Dendrite formation leads to cell short circuits, higher rates of adverse reactions, and large volume changes. These problems are major safety issues but also account for the low Coulombic efficiency and poor cycling performance2. The utilization of all-solid-state cells for lithium batteries can reduce the growth of dendrites3, which greatly improves safety2. However, solid-state batteries suffer from high resistances at ambient temperatures. Wu et al.4 studied an all-solid-state battery composed of a lithium foil anode and a cathode made of lithium ferric phosphate (LFP) particles in a block copolymer matrix. In the cathode, the electronic conduction is facilitated by a conducting polymer, poly(3-hexylthiophene) (P3HT). The conductivity of this semiconductor polymer depends on the electrode potential because the conducting polymer is oxidized and reduced when transporting the electrons. The electronic conductivity of the cathode polymer matrix without the LFP active particles was measured as a function of the voltage, and this experimental fit was used with a macro-homogeneous continuum model developed by Newman and associates5,6. The model output was relatively independent of the rate and failed to capture the trend of the experimental data. The authors then reduced the electronic conductivity until the best agreement between the experimental data and the model was achieved4. This talk explores the possibility of obtaining better fits for the model predictions by performing detailed estimation of different parameters that affect the performance of the system by combining different/robust simulation and estimation methods. Acknowledgments The authors are thankful for the financial support from the Battery 500 Consortium and the Clean Energy Institute (CEI) at the University of Washington. References Takada, K., AIP Conf. Proc., 1765, (2016).Cheng, X. B., Zhang, R., Zhao, C. Z. & Zhang, Q., Chem. Rev., 117, 10403–10473 (2017).Kim, J. G. et al., J. Power Sources, 282, 299–322 (2015).Wu, S.-L., Javier, A. E., Devaux, D., Balsara, N. P. & Srinivasan, V. J., Electrochem. Soc., 161, A1836–A1843 (2014).Newman, J. S. & Tobias, C. W., J. Electrochem. Soc., 109, 1183 (1962).Doyle, M., Fuller, T. F. & Newman, J., J. Electrochem. Soc., 140, 1526 (1993).

Anti-Tumor Necrosis Factor-α-Induced Dermatological Complications in a Large Cohort of Inflammatory Bowel Disease Patients.

The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients. This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included. From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42±13years), 85% with Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27-77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR=1.658, p=0.029), smoking (OR=2.021, p=0.003), and treatment with an infliximab dose of 10mg/kg (OR=2.012, p=0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR=3.63, p=0.017), smoking (OR=2.846, p=0.041), and treatment with adalimumab (OR=8.894, p<0.001) were independently associated with development of psoriasiform lesions. Three (3%) patients with infectious complications and 12 (31%) patients with psoriasiform lesions discontinued anti-TNF therapy definitively. Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.