Real Efficacy Research Articles

Li-Eswt improves hemodynamic parameters thus suggesting neoangiogenesis in patients with vascular erectile dysfunction.

Extracorporeal treatment with low intensity shock-wave therapy (LI-ESWT) is a recently introduced non-invasive method which purposes the restoration of the pathophysiological alterations at the base of vasculogenic ED in male patients. The evidence in favour of the neoangiogenic potential of this treatment derived from in vitro studies and on animal models. The purpose of this study, in which the Power Doppler method was applied, is to demonstrate 'objectively' the real efficacy of LI-ESWT at the level of the microcirculation of the corpora cavernosa (neoangiogenesis) in patients affected by vasculogenic ED. Data from this study show, for the first time, that LI-ESWT treatment promotes neovascularisation of the functional arteries in patients affected by vasculogenic ED.

Abstract PS10-40: Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

Abstract BackgroundPalbociclib, a highly selective inhibitor of CDK4/6, is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with an aromatase inhibitor or with fulvestrant for patients who have progressed with an aromatase inhibitor, and in premenopausal women with a luteinising-hormone-releasing-hormone (LH-RH) agonist. Emerging real world data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report here the Institut Curie (IC) experience. Patients and methodsWe retrospectively reviewed all patients with HR+ HER2- ABC treated with a palbociclib-based therapy as 1st or 2nd line of therapy for ABC, from November 2016 to December 2018. Clinical, biological and imaging data were retrieved from IC electronic health record system. Data lock was December 31st 2020. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. ResultsWe included 310 consecutive premenopausal (24.5%) and menopausal (75.5%) women. Median age was 61.8 years-old [23.5-92.1]. Among them, Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 59.7%, 1 in 32.1%, and 2 in 8.2% of patients (pts). The ABC diagnosis was de novo for 26.8%. There was at least one visceral lesion in 51.0% of pts, only bone lesions in 30.3%, 28.1% had three metastatic sites or more, and none of them have brain lesions. Previous treatments were chemotherapy (49.4%) and endocrine therapy (60.7%). Among pts pretreated by at least one endocrine therapy, 51.1% had shown prior sensibility, as defined by an absence of recurrence during adjuvant endocrine therapy or during 24 months after its completion, or an absence of progression during 6 months after the beginning of an endocrine therapy for a metastatic disease. Palbociclib was prescribed in the 1st line setting for 72.6% of pts and in the 2nd line setting for 27.4% of pts. The initial dose was 125 mg daily (95.2%). It was associated with an aromatase inhibitor (66.8%) or with fulvestrant (33.2%). LH-RH agonist was prescribed in 19.7% of pts. Denosumab was prescribed in 68.5% of pts with bone lesions. Median follow-up was 20.7 months (m). At 12 m from the initiation of palbociclib, 94.5% of the pts were alive. Median progression free survival was 23.4 m (95%CI: 21.6-NR) for pts without previous endocrine therapy, 22.7 m (95%CI: 14.7-NR) for pts who have shown endocrine sensibility, HR=1.2 (95%CI: 0.81-1.77), p=0.0027 and 13.4 m (95%CI: 10.7-20.8) for pts who have not shown endocrine sensibility, HR=1.88 (95%CI: 1.29-2.73), p=0.003. Although sensibility to previous endocrine therapy was a prognostic factor for progression free survival with the univariate analyse, it was not with the multivariate analysis. Three independent poor prognostic factors for progression free survival were identified: previous chemotherapy, HR=1.6 (95%CI: 1.12-2.29), p<0.001; initial ECOG performance status 2, HR=2.72 (95%CI: 1.55-4.79), p<0.001; and three or more metastatic sites, HR=1.61 (95%CI: 1.152.26), p<0.001. Hematologic grade 3-4 adverse events were neutropenia (72.3%), leukopenia (43.9%), anemia (3.2%) and thrombocytopenia (2.9%). Other adverse events observed (all grades) were infections (16.5%), stomatitis (13.9%) or alopecia (13.9%). At least one dose reduction occurred in 29.4% of pts and permanent discontinuation because of treatment toxicity was observed in 5.7% of pts. ConclusionIn a non-selected population of patients with HR+ HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported. Palbociclib, in combination with hormone therapy, is a cornerstone treatment of HR+ HER2- metastatic breast cancer. Citation Format: Baptiste Porte, Matthieu Carton, Delphine Loirat, François-Clement Bidard, Linda Haroun, Audrey Bellesoeur, Youlia Kirova, Paul Cottu. Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-40.

Injectable hydrogels of newly designed brush biopolymers as sustained drug-delivery vehicle for melanoma treatment

Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic–hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.

Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review.

Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic hyperhidrosis. Recently, botulinum toxins have also been used in many other skin diseases, in off label regimen. The objective of this manuscript is to review and analyze the main therapeutic applications of botulinum toxins in skin diseases. A systematic review of the published data was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Botulinum toxins present several label and off-label indications of interest for dermatologists. The best-reported evidence concerns focal idiopathic hyperhidrosis, Raynaud phenomenon, suppurative hidradenitis, Hailey–Hailey disease, epidermolysis bullosa simplex Weber–Cockayne type, Darier’s disease, pachyonychia congenita, aquagenic keratoderma, alopecia, psoriasis, notalgia paresthetica, facial erythema and flushing, and oily skin. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and doses protocols for off label applications.

Contribution of Drugs Interfering with Protein and Cell Wall Synthesis to the Persistence of Pseudomonas aeruginosa Biofilms: An In Vitro Model.

The occurrence of Pseudomonas aeruginosa (PA) persisters, including viable but non-culturable (VBNC) forms, subpopulations of tolerant cells that can survive high antibiotic doses, is the main reason for PA lung infections failed eradication and recurrence in Cystic Fibrosis (CF) patients, subjected to life-long, cyclic antibiotic treatments. In this paper, we investigated the role of subinhibitory concentrations of different anti-pseudomonas antibiotics in the maintenance of persistent (including VBNC) PA cells in in vitro biofilms. Persisters were firstly selected by exposure to high doses of antibiotics and their abundance over time evaluated, using a combination of cultural, qPCR and flow cytometry assays. Two engineered GFP-producing PA strains were used. The obtained results demonstrated a major involvement of tobramycin and bacterial cell wall-targeting antibiotics in the resilience to starvation of VBNC forms, while the presence of ciprofloxacin and ceftazidime/avibactam lead to their complete loss. Moreover, a positive correlation between tobramycin exposure, biofilm production and c-di-GMP levels was observed. The presented data could allow a deeper understanding of bacterial population dynamics during the treatment of recurrent PA infections and provide a reliable evaluation of the real efficacy of the antibiotic treatments against the bacterial population within the CF lung.

Biologic Augmentation Reduces the Failure Rate of Meniscal Repair: A Systematic Review and Meta-analysis.

Background:Clinical results after isolated meniscal repair are not always satisfactory, with an overall failure rate of around 25%. To improve the success rate of meniscal repair, different biologic augmentation techniques have been introduced in clinical practice, but their real efficacy is still controversial.Purpose/Hypothesis:To evaluate the safety, clinical results, and failure rate of biologic augmentation techniques for meniscal repair. The hypothesis was that biologic augmentation would improve the results of meniscal repair.Study Design:Systematic review and meta-analysis of comparative studies.Methods:A systematic review of the literature was performed in March 2020 of 3 electronic databases (PubMed, Scopus, and the Cochrane Library) regarding meniscal repair combined with biologic augmentation techniques. Articles combining biologic augmentation with other surgical procedures besides meniscal suture were excluded. The quality of the included studies was assessed using a modified Coleman Methodology Score, and the risk of bias was evaluated using the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) and the RoB 2.0 (Revised Tool for Risk of Bias in Randomized Trials) for nonrandomized and randomized controlled trials, respectively.Results:A total of 11 studies were included in the qualitative analysis: platelet-rich plasma (PRP) augmentation in 6 comparatives studies, fibrin clot augmentation in 2 case series, and mesenchymal stem cells augmentation in 2 case series and 1 case report. One severe adverse event of septic arthritis was reported for PRP 1 month after surgery. The quality of evidence evaluated with the modified Coleman Methodology Score was low overall. Five studies reporting on 286 patients (111 PRP augmentation, 175 control) were included in the quantitative synthesis. A significantly lower risk of failure was documented in the PRP augmentation group as compared with the control group: 9.9% (4.5%-19.1%) versus 25.7% (12.7%-38.7%) (P < .0005).Conclusion:The literature on biologic meniscal augmentation is recent and scarce. Only a few comparative trials are available, all focusing on the potential of PRP. The meta-analysis documented that PRP is safe and useful in improving the survival rate, with a 9.9% rate of failure versus 25.7% for the control group. Further high-level studies are needed to confirm these findings and identify the most effective biologic augmentation strategy to improve the outcome of meniscal repair.

Corporate Exercise and the Borders of Privilege: The Trades of Paris in the Seventeenth and Eighteenth Centuries

The efficacy of privilege under the Old Regime, especially as concerning the economy, is an oft-repeated postulate of historiography. The contexts in which it was used often came under the activities of the law or the police, and the privilege of guilds was far from being any exception. There were many struggles in activating these privileges, due to their near-permanent disputation, a disputation which constituted the very heart and the viability of corporatism. This is why we must investigate the application of these privileges. At the same time, without renouncing the idea their real efficacy, we must displace them to their own margins, their borders. At their outer limits, privileges stood in opposition to other trades, which were thus excluded from such and such a sector of sale or manufacture. This did not result in the application of norms and qualities to a finite set of merchandise and commercial positions. Rather, trade privileges were mainly aimed at precluding others from these same norms and qualities, the same merchandise and postures. Privilege also served to blur the indeterminate lines of demarcation concerning those same elements with regards to the holder of said privilege. Thus, we must look at this border as the site of a real social connection, where professional identities and individual careers were continually brought into play, and where, especially, the border between merchant/craftsman categories was constantly shifting.

Comprehensive and safe school strategy during COVID-19 pandemic

BackgroundAlthough several studies have tried to evaluate the real efficacy of school closure for pandemic control over time, no definitive answer to this question has been given. Moreover, it has not been clarified whether children or teenagers could be considered a problem for SARS-CoV-2 diffusion or, on the contrary, whether parents and school workers play a greater role. The aims of this review are to discuss about children’s safety at school and the better strategies currently able to reduce the risk of SARS-CoV-2 infection at school.Main aimCompared to adults, very few cases of COVID-19 were diagnosed in children, who generally suffered from an asymptomatic infection or a mild disease. Moreover, school closure is systematically associated with the development of problems involving students, teachers and parents, particularly among populations with poor resources. Although several researches have tried to evaluate the real efficacy of school closure for pandemic control over time, no definitive answer to this question has been given. Available findings seem to confirm that to ensure adequate learning and to avoid social and economic problems, schools must remain open, provided that the adults who follow children at home and at school absolutely comply with recommendations for prevention measures and that school facilities can be optimized in order to significantly reduce the spread of infection. In this regard, the universal use of face masks in addition to hand hygiene and safe distancing in schools, at least starting from the age of 6 years, seems extremely useful. Moreover, since the beginning of the COVID-19 outbreak the use of telemedicine to manage suspected SARS-CoV-2-infected individuals in the community has appeared to be an easy and effective measure to solve many paediatric problems and could represent a further support to schools .ConclusionsWe think that schools must remain open, despite COVID-19 pandemic. However, several problems strictly related to school frequency and reduction of infectious risk must be solved before school attendance can be considered completely safe. A single more in-depth guideline agreed between countries with the same school problems could be very useful in eliminating doubts and fostering the compliance of students, teachers and non-teaching school staff reducing errors and misinterpretations.

RETRACTED: Embedded IoT system and functional recovery of sports spinal cord injury

The ultimate goal of clinical review, including clinical reviews and Spinal Cord Injury (SCI), is to improve the general ability of people who live and continue to work for SCI. Neurological rehab does not usually turn into adequate rest. The main outcome assessments aimed at in these approaches are the actual scenarios to be developed concerning SCI. Technology: The global set of tasks currently enters the evaluation of SCI utility outcomes activities. Spinal Cord Injury (SCI) is an injury to the spinal cord from the superior to the caudal fossa. This is because of the stimulus, entry points or bruises. SCI car crashes on the planet, shooting injuries, injury knives, the most well-known causes of falls and sports trauma. If the injury is complete, there is a strong correlation between the effectiveness levels, such as the injury's size. SCI combines detrimental independence and real efficacy effects, but it also combines many difficulties with injuries. There are many nerve energy accelerators in the bladder and viscera, urinary tract infections, bedsores, sinusitis, rest, deep venous stroke, seizures, abnormal autonomic reflex, pneumonia and heart problems, and complications are not a recurring problem after spinal cord injury. It asks any job loss that brings vulnerable patients will bring up psychological and monetary issues. The treatment and recovery cycle is costly and lengthy, which also hurts the lifespan of SCI. Early recovery is essential to prevent joint wrinkles and loss of muscle mass, bone thickness protection, and ensure normal functioning of the trachea and abdomen related structure. With a multidisciplinary approach, there are different types of restructuring based on SCI restructuring.

The real UVB photoprotective efficacy of vegetable oils: in vitro and in vivo studies.

Some vegetable oils are currently being promoted as a safe alternative to commercial sunscreens. The true UVB photoprotective efficacy of 14 virgin vegetable oils and the suitability of the dilution method for determining their SPF value were evaluated. Oils and standard sunscreens were investigated in vitro by the Mansur's method in Slovakia and in vivo by the ISO method in the Czech Republic. SPF values in vitro (0.1; 0.0; 0.4; 0.2 and 0.2) and in vivo (2.5; 1.2; 2.6; 2.6; and 2.8) of the five most promoted oils (from carrot seed, coconut, raspberry seed, rosehip seed, and wheat germ) were significantly lower than the values reported in the controversial studies. We have shown that the overestimated SPF values of these oils were determined by authors who did not strictly follow Mansur's original methodology. The other eight vegetable oils also provide no or negligible SPF values. Only the in vitro SPF value of 11.2 tamanu oil is worth mentioning, probably due to high proportion of calophyllolides. In vitro and in vivo SPF ratios from 1.14 to 0.94 obtained by two methods in two laboratories for six commercial sunscreen oils used as controls confirm the correctness of performing the Mansur's method in this study. However, this dilution method has proven to be fundamentally flawed in determining the SPF value of substances with such negligible photoprotection as most vegetable oils can provide. An SPF value of less than 1, which can be determined by this Mansur's method, is physiologically impossible and meaningless.

A Potent Inhibitor of IL-10/STAT3 Axis Signaling Modulates Anti-Inflammatory Responses and Boosts Anti-Tuberculosis Immunity in rBCG30 Immunized Mice

Aims and Objectives: In the present study we tried to improve anti-TB immunity offered by 2nd generation rBCG30 vaccine. We attempted to bolster rBCG30 invoked anti-TB immunity in mice through modulation of the IL-10/STAT3 interaction mediated anti-inflammatory program. The study was aimed towards generating optimum activated APCs, early either after vaccination (with rBCG30) or infection (with Mtb), which can process and present mycobacterial antigens more efficiently to T cells. It was envisage that downmodulating IL-10/STAT3 signaling may improve immunity and protection offered by rBCG30 vaccine. Methods: A small molecule immunomodulator aimed at disrupting anti-inflammatory signaling orchestrated by IL-10/STAT3 axis was administered in rBCG30 immunized mice. The comparative expansion of pathogen permissive Alternatively Activated Monocytes/Macrophages/DCs (AAMs/AADCs) and Classically Activated Monocytes/Macrophages/DCs (CAMs/CADCs), the cells that resist establishment of successful Mtb infection, was profiled in both peritoneal and splenic compartment. To assess innate and adaptive T cell responses, splenocytes cytokine production was checked ex vivo using sandwich ELISA. We also checked polyfunctional T cell response, T cell memory response and comparative Th17/Treg cells expansion using flow cytometry. Finally, to assess the real time efficacy of the employed immunotherapeutic strategy, in vivo protection study was undertaken in BALB/c mice challenge with aerosolized Mtb (H37 Rv). Results: The small molecule mediated inhibition of IL-10/STAT3 signaling was resulted in improved pro inflammatory immune responses in both post-vaccination and post-infection immunotherapy schedules. The improved immune profile in rBCG30 vaccinated and immunotherapy administered mice was accompanied with enhanced expansion of CAMs/CADCs, elevated production of polyfunctional T cells producing signature Th1 cytokines, long lasting CD4+ and CD8+ memory T cell response and balanced Th17/Treg cells ratio. Interestingly, post-infection, and not post-vaccination immunotherapy, was able to significantly reduce mycobacterial loads in spleen and lungs of experimentally infected mice. Conclusions: Small molecule mediated transient disruption of anti-inflammatory effectors, such as IL-10/STAT3, during vaccination or post infection with Mtb, may serve to enhance the efficacy of existing and forthcoming TB vaccines. The strategy can also be tested concomitantly with standard chemotherapy (either in vaccinated or unvaccinated host) to enhance the efficacy of therapeutic regimen and to reduce the treatment length.

Expert opinion: Using of antiplatelet agents in surgery with external fixators

Expert opinion: Using of antiplatelet agents in surgery with external fixators

729. Real World Efficacy of Bezlotoxumab for Prevention of Clostridioides Difficile Recurrence in Immunosuppressed Patients

BackgroundBezlotoxumab has been shown to prevent recurrent episodes of C. difficile infection (CDI) in high risk patients. Current studies define therapeutic efficacy within the first 12 weeks when the risk of recurrence is greatest. However, the risk of recurrent CDI can occur beyond the 12-week window in the immunosuppressed population. Given that bezlotoxumab has detectable serum levels for up to 24 weeks after infusion, the primary endpoint is to determine overall efficacy in immunosuppressed patients with recurrent CDI at 4 weeks, 12 weeks, and 24 weeks after initial infusion. Secondary endpoints consist of risk factors for recurrent CDI, treatment of CDI, and antibiotics usage before and after bezlotoxumab.MethodsThis analysis included immunosuppressed patients at high risk for CDI recurrence who received bezlotoxumab from February 2017 to December 2019. Patients were excluded if they were not immunosuppressed, had no follow-up appointments, and/or without a C. difficile positive test. High risk antibiotics included fluoroquinolones, beta lactamase inhibitors, third generation cephalosporins, or carbapenems.ResultsTwenty-seven bezlotoxumab doses were given to 26 patients. Baseline characteristics for CDIs prior to bezlotoxumab is reported in Table 1. The overall CDI recurrence rate at all intervals after bezolotoxumab was 4 (15%), one recurrent CDIs occurred at < 4 weeks, two recurrent CDIs occurred at 5-12 weeks, and one recurrent CDI at 13-24 weeks. High risk antibiotics were given in 2/4 (50%) of CDIs recurrences and 22/75 (29%) in the non-recurrence group. Of the four CDI recurrences, all were mild to moderate in disease severity given no evidence of colitis was seen on CT scan and a median Zar score of 1 (range 0-1) due to age > 60 years.Table 1: Baseline Characteristics ConclusionIn immunosuppressed patients with CDI, bezlotoxumab is effective at reducing CDI episodes up to 24 weeks. Additionally, this highly antibiotic exposed population continued to receive benefit up to 24 weeks after bezlotoxumab.Disclosures All Authors: No reported disclosures

Management of dermatophytosis with a novel itraconazole formulation: a research survey

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Dermatophytic infections are the most prevalent fungal infections, which affect majority of the global population. Indian climate, especially the hot and humid conditions contribute majorly to dermatophytosis. Itraconazole is an orally active triazole antifungal drug, which has demonstrated a broad spectrum of activity and a favourable pharmacokinetic profile. Itraconazole at an appropriate dosage and duration schedule has been reported to be an effective antifungal drug and has achieved optimal results.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The present survey aimed at evaluating the efficacy of the novel itraconazole formulation,&lt;/p&gt;&lt;p class="abstract"&gt;I-Tyza 100 [itraconazole 100 mg (Abbott health care pvt ltd)] with multi-particulate in solid dispersion (MPSD) technology in patients with tinea infections. The data collection was based on the proportion of patients presenting in the clinics for tinea infections, the choice and duration of therapy, real life efficacy of the drug, and for understanding the overall antifungal therapy in dermatomycosis.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The responses obtained from 177 doctors were evaluated, and statistical analyses were carried out. The results suggested that clinical presentation of patients with tinea infections per week ranged between 30% and 60%. For the management of tinea infections, oral itraconazole was preferred by maximum doctors, followed by terbinafine, griseofulvin and fluconazole. Also, majority of the doctors (83%) opined that MPSD technology could improve therapeutic efficacy of the novel itraconazole formulation.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The survey findings indicated that the novel itraconazole formulation is a preferred oral antifungal therapy for the management of tinea infections.&lt;/p&gt;

Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review.

Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic Tlymphocyte antigen4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis). A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar. The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain. Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug.

Controversies about the cardiovascular effects of OM3FA. Did inappropriate placebos skew clinical trial results?

Several observational studies suggest that greasy fish may reduce cardiovascular risk, whose benefits have been attributed to the presence Omega-3 polyunsaturated fatty acids (OM3FA). However, there are some randomized controlled trials (RCTs) that have shown contradictory results concerning the cardiovascular benefits of OM3FA. Analyzing these RCTs we found that the use of olive oil in some RCTs could be responsible for contradictory results, since both.since both olive oil and OM3FA, in addition to reduce triglycerides, have anti-platelet and anti-inflammatory activities, considered important for the stabilization of atherosclerotic plaques. This pharmacodynamic profile may have a cardio protective effect that was confirmed by several RCTs. Therefore, olive oil seems an active substance, and its use might have reduced the differences between groups masking the efficacy of OM3FA. This inferred lack of OM3FA cardiovascular benefits due to bias induced by a “false placebo” control, raises epistemological considerations on the choice of placebos that always should be pharmacologically inert substances.More studies are necessary to clarify the real efficacy of OM3FA that is more innocuous than many medicines, but it seems useful in future RCTs the use of a truly inert substance as a placebo, as well as the outline of a semi quantitative dose-response curve suggestive of a causal nexus between active substances and their outcomes.

Drug Prices, Dying Patients, and the Pharmaceutical Marketplace: A New Conditional Approval Pathway for Critical Unmet Medical Needs

Prescription drugs are much in the news these days. There are two topics which appear very often; first, the very high prices of new drugs, particularly the “specialty” drugs developed for serious diseases; and second, the time required for FDA approval in relation to the perceived need for earlier access to new therapies for critically ill patients. Much less in the news, but lurking behind both problems, is the need for better information for physicians and patients to use in making decisions about prescribing and taking drugs and for insurance companies and the government to use to structure their pharmaceutical benefits plans. This article proposes an approach to both accelerated access and drug prices that would generate the information doctors and patients need to make decisions about drugs and the information the government and private insurers need to provide appropriate access and coverage for those drugs. The new form of conditional approval proposed here would be similar to the parallel track program developed by the FDA in the 1990s, during the HIV crisis. I argue that, like parallel track, the conditional approval proposed here could be implemented by the FDA under its existing authority, allow wide access to desperately needed drugs, and would control prices while providing better information about the real safety and efficacy of new drugs for critically ill patients.

Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion mutations

ObjectivesEpidermal growth factor receptor (EGFR) exon 20 insertion (ex20 ins) mutations are generally associated with de novo resistance to first- or second-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the real efficacy of osimertinib for this subset remains elusive. We performed this study to investigate the real efficacy of osimertinib for Chinese advanced NSCLC patients harboring EGFR ex20 ins mutations. Materials and methodsWe retrospectively collected data of metastatic NSCLC patients with EGFR ex20 ins mutations who were treated with osimertinib 80 mg or 160 mg once daily in our center from June 2017 to May 2020. Progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. ResultsA total of 62 cases with EGFR ex20 ins mutations were included, and the major insertion variant was D770_N771insSVD and V769_D770insASV (45.1 %). Concurrent TP53 mutation was most commonly observed (59.7 %). Four patients showed partial response, 29 cases with stable disease and 29 showed progressive disease as best response to osimertinib (ORR: 6.5 %, DCR: 53.2 %). The median PFS (mPFS) in total patients was 2.3 (95 %CI, 1.5–3.1) months. Patients harboring A763_Y764insFQEA/D770delinsGY variants showed numerically longer mPFS than those with other variants (4.2 vs. 2.2 months, P = 0.164). Patients who failed to osimertinib and occurred extracranial progression showed similar mPFS to those with intracranial progression (2.3 vs. 1.9 months, P = 0.142). Median PFS was not significantly different between patients who received osimertinib 80mg or 160mg once daily (2.5 vs. 1.3 months, P = 0.161), either with no significance when it used in fist-line setteing or bove (3.0 vs. 2.2 months, P = 0.639). ConclusionThe unique insertion variant A763_Y764insFQEA and D770delinsGY might better respond to osimertinib than other ex20 ins subtypes. Osimertinib either 80 mg or 160 mg once daily showed less activity in Chinese NSCLC patients harboring diverse EGFR ex20 ins mutations.

PP349 Use Of Applications For Mobile Devices In Asthma Control: A Systematic Review Of Literature

IntroductionCell phones and information technology can be allies in the care of chronic diseases. Despite the wide availability of mobile device applications (apps), many offered by industry and providers, questions remain about the real efficacy of these technologies. The objective of this study was to evaluate the efficacy of mobile device apps designed for use by outpatients in treatment for asthma and describe its main characteristics and functionalities.MethodsA systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was conducted. MEDLINE and EMBASE were searched for randomized clinical trials (RCTs) evaluating the adoption of mobile apps on Android or iOS systems compared to the usual care, published in the last five years. Asthma control rate was defined as the primary outcome, and visits to emergency departments, hospitalizations and adherence to pharmacological treatment were secondary outcomes.ResultsFour RCTs (n = 415) met the inclusion criteria, two involving children and adults, and two only adults. Methodological quality was low to moderate. Common functionalities were asthma action plans, registration of the usual treatment, symptom diaries and educational alerts. Results were heterogeneous with respect to all outcomes evaluated. Study dropouts and lack of follow-up were frequent.ConclusionsThe clinical utility of mobile apps for asthma was evaluated in a few randomized studies; more data are necessary to establish the value of these technologies for asthma control.

Medical Approaches in Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) represents one of the most aggressive endocrine tumors. In spite of a correct therapeutic strategy based on a multidisciplinary approach between endocrinologist, surgeon and oncologist, the prognosis is often poor. Surgery is the mainstay treatment in ACC. Mitotane, a dichloro-diphenyl-trichloro-ethane derivate, represents the main medical treatment of ACC in consideration of its adrenocytolitic activity and it is mainly employed as adjuvant treatment after complete surgical resection and for the treatment of advanced ACC. However, the use of mitotane as adjuvant therapy is still controversial, also in consideration of the retrospective nature of several studies. The recurrence of disease is frequent, especially in advanced disease at the diagnosis. Therefore, in these contexts, conventional chemotherapy must be considered in association with mitotane, being the combination etoposide, doxorubicin and cisplatin (EDP) the standard of care in this setting. A more modern therapeutic approach, based on the need of a salvage therapy for advanced ACC that progresses through first-line EDP, is focused on molecular-targeted therapies. However, robust clinical trials are necessary to assess the real efficacy of these treatments.