Different Levels Of Efficacy Research Articles

Designing a model to estimate the burden of COVID-19 in Iran

The novel coronavirus disease 2019 (COVID-19) is the latest evidence of an epidemic disease resulting in an extraordinary number of infections and claimed several lives, along with extensive economic and social consequences. In response to the emergency situation, countries introduced different policies to address the situation, with different levels of efficacy. This paper outlines the protocol for developing a model to analyze the burden of COVID-19 in Iran and the effect of policies on the incidence and cumulative death of the disease. The importance of the model lies in the fact that no study, according to the authors’ best knowledge, tried to quantify the impact of the disease on Iran society and the impact of various implemented interventions on disease control. Based on a systematic review of COVID-19 prediction models and expert interviews, we developed a system dynamics model that not only includes an epidemic part but also considers the impact of various policies implemented by the Ministry of Health. The epidemic model estimates the incidence and mortality of COVID-19 in Iran. The model also intends to evaluate the effect of implemented policies on these outcomes. The model reflects the continuum of COVID-19 infection and care in Iran (of which some of its elements are unique) and key activities and decisions in delivering care. The model is calibrated and validated using data published by the Ministry of Health of Iran. Finally, the study aims to provide evidence of the impact of interventions intended to curb COVID-19 in Iran. Insights provided by the model will be necessary for controlling either future waves of the disease or similar future pandemics.

Personalized Use of Disease-Modifying Therapies in Multiple Sclerosis.

Multiple sclerosis is an important neurological disease affecting millions of young patients globally. It is encouraging that more than ten disease-modifying drugs became available for use in the past two decades. These disease-modifying therapies (DMTs) have different levels of efficacy, routes of administration, adverse effect profiles and concerns for pregnancy. Much knowledge and caution are needed for their appropriate use in MS patients who are heterogeneous in clinical features and severity, lesion load on magnetic resonance imaging and response to DMT. We aim for an updated review of the concept of personalization in the use of DMT for relapsing MS patients. Shared decision making with consideration for the preference and expectation of patients who understand the potential efficacy/benefits and risks of DMT is advocated.

Hybrid deep model for predicting anti-cancer drug efficacy in colorectal cancer patients

Cancers are genetically diversified, so anticancer treatments have different levels of efficacy on people due to genetic differences. The main objective of this work is to predict the anticancer drug efficiency for colorectal cancer patients to reduce the mortality rates and provides immune energy for the patients. This paper proposes a novel anti-cancer drug efficacy system in colorectal cancer patients. The input data gene is normalized with the Min–Max normalization technique that normalizes the data in distinct scales. Subsequently, proposes an improved entropy-based feature to evaluate the uncertainty distribution of data, in which it induces weight to overcome the issue of computational complexity. Along with this feature, a correlation-based feature and statistical features are also retrieved. Subsequently, proposes a Recursive Feature Elimination with Hybrid Machine Learning (RFEHML) mechanism for selecting the appropriate feature set by eliminating the recursive features with the aid of hybrid Machine Learning strategies that combine decision tree and logistic regression. Also, the Gini impurity is employed for ranking the feature and selecting the maximum importance score by eliminating the least acquired importance score. Further, proposes a hybrid model for predicting the drug efficiency with the trained feature set. The hybrid model comprises of Long Short-Term Memory (LSTM) and Updated Rectified Linear Unit-Deep Convolutional Neural Network (UReLU-DCNN) model, in which DCNN is modified by updating the activation function at the fully connected layer. Consequently, the learned feature predicts the drug efficacy of anti-cancer in colorectal cancer patients by determining whether the patient is a responder or non-responder of the drug. Finally, the performance of the proposed RFEHML model is compared with other traditional approaches. It is found that the developed method has higher accuracy for each learning percentage, with values of 60LP = 92.48%, 70LP = 94.28%, 80LP = 95.24%, and 90LP = 96.86%, respectively.

Glufosinate and diquat in pre-harvest desiccation of soybean at four phenological stages, and their impact on seed quality

Glufosinate and diquat may have different levels of efficacy in the pre-harvest desiccation of soybean (Glycine max (L.) Merr.) plants, and may affect quality of seeds differently, depending on the phenological stage at which they are applied. The objective of this study was to evaluate desiccation with glufosinate and diquat at the phenological stages R6, R7.1, R7.2, and R7.3, and to examine their effects on yield and quality of soybean seeds. The experiment was conducted at two sites in the state of Paraná (PR), Brazil, in the 2020-2021 crop season. A randomized block design was used, treatment groups consisted of application of glufosinate or diquat at R6, R7.1, R7.2, and R7.3, and the control group (without desiccant application). Defoliation, maturity, moisture, yield, and seed quality (vigor and germination) were evaluated. Glufosinate and diquat were effective at desiccation and had a significant effect on defoliation and maturity, with final values ≥ 98.8% and ≥ 99.3% respectively. Treatments can accelerate harvest maturity by approximately 3 d and earlier applications do not necessarily favor this acceleration, most notably in trial 1. However, desiccation at earlier stages reduced seed yield and negatively affected seed quality, with values of only 61.3% and 71.8% of vigor and germination in some situations. The application of glufosinate or diquat was effective in the pre-harvest desiccation of soybean plants, with no differences between the assessed herbicides or phenological stages. The application of glufosinate starting at R7.2 or diquat at R7.3 is ideal to avoid deleterious effects on seed yield. Applications at earlier stages may lead to losses of more than 30% seed yield. The use of diquat or glufosinate before R7.2 may reduce the quality of seeds.

Changes in the psychological defense mechanism and clinical features of patients with OCD – A four-year follow-up study

ObjectiveThe present study aims to (1) follow up with 4-year changes in the efficacy outcome, defense style questionnaire (DSQ) score, and clinical features of patients with obsessive-compulsive disorder (OCD) and (2) analyze the relationship between different levels of efficacy and changes in the patients' psychological defense mechanisms. MethodsThe following data collection and 4-year follow-up were completed for 153 patients with OCD: (1) the treatment process, efficacy outcome, course of disease, and clinical features of OCD were collected using a self-made general information questionnaire and (2) the control method was used to analyze the changes in clinical symptoms (Yale–Brown obsessive compulsive scale [YBOCS], Hamilton anxiety score [HAMA], and Hamilton depression scale [HAMD]) in patients with OCD. Moreover, the changes in the psychological defense mechanism (measured by DSQ) and the relation between the prognosis and DSQ score were investigated. Results(1) The HAMA score (8.7 ± 4.8 points), HAMD score (12.0 ± 6.6 points) and YBOCS score (16.4 ± 8.4 points) were significantly lower during the follow-up than at the time of enrollment (p < 0.01). In the two DSQ evaluations, there were no significant differences in the factors, with the exception of a significant decrease in the use of “reaction formation” (t = 2.533, p = 0.015). The changes of mature defense factors in the significant efficacy group significantly increased (p < 0.01). Which was mainly manifested in the significant increase in the score of “sublimation” item, and the difference was extremely significant (t = −3.093, p = 0.006). ConclusionAn abnormal psychological defense mechanism plays an important role in OCD, and the use of a mature defense mechanism is significantly related to the treatment efficacy.

Finding the Perfect Fit: Conformational Biosensors to Determine the Efficacy of GPCR Ligands.

G protein-coupled receptors (GPCRs) are highly druggable targets that adopt numerous conformations. A ligand's ability to stabilize specific conformation(s) of its cognate receptor determines its efficacy or ability to produce a biological response. Identifying ligands that produce different receptor conformations and potentially discrete pharmacological effects (e.g., biased agonists, partial agonists, antagonists, allosteric modulators) is a major goal in drug discovery and necessary to develop drugs with better effectiveness and fewer side effects. Fortunately, direct measurements of ligand efficacy, via receptor conformational changes are possible with the recent development of conformational biosensors. In this review, we discuss classical efficacy models, including the two-state model, the ternary-complex model, and multistate models. We describe how nanobody-, transducer-, and receptor-based conformational biosensors detect and/or stabilize specific GPCR conformations to identify ligands with different levels of efficacy. In particular, conformational biosensors provide the potential to identify and/or characterize therapeutically desirable but often difficult to measure conformations of receptors faster and better than current methods. For drug discovery/development, several recent proof-of-principle studies have optimized conformational biosensors for high-throughput screening (HTS) platforms. However, their widespread use is limited by the fact that few sensors are reliably capable of detecting low-frequency conformations and technically demanding assay conditions. Nonetheless, conformational biosensors do help identify desirable ligands such as allosteric modulators, biased ligands, or partial agonists in a single assay, representing a distinct advantage over classical methods.

Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious.We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types.A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49–8.93; I2 = 29%, P = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56–4.42; I2 = 0, P = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99–10.29; I2 = 0, P = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences.In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Chemical Characterization and Bioactivity of Commercial Essential Oils and Hydrolates Obtained from Portuguese Forest Logging and Thinning.

Essential oils (EOs) and hydrolates (Hds) are natural sources of biologically active ingredients with broad applications in the cosmetic industry. In this study, nationally produced (mainland Portugal and Azores archipelago) EOs (11) and Hds (7) obtained from forest logging and thinning of Eucalyptus globulus, Pinus pinaster, Pinus pinea and Cryptomeria japonica, were chemically evaluated, and their bioactivity and sensorial properties were assessed. EOs and Hd volatiles (HdVs) were analyzed by GC-FID and GC-MS. 1,8-Cineole was dominant in E. globulus EOs and HdVs, and α- and β-pinene in P. pinaster EOs. Limonene and α-pinene led in P. pinea and C. japonica EOs, respectively. P. pinaster and C. japonica HVs were dominated by α-terpineol and terpinen-4-ol, respectively. The antioxidant activity was determined by DPPH, ORAC and ROS. C. japonica EO showed the highest antioxidant activity, whereas one of the E. globulus EOs showed the lowest. Antimicrobial activity results revealed different levels of efficacy for Eucalyptus and Pinus EOs while C. japonica EO showed no antimicrobial activity against the selected strains. The perception and applicability of emulsions with 0.5% of EOs were evaluated through an in vivo sensory study. C. japonica emulsion, which has a fresh and earthy odour, was chosen as the most pleasant fragrance (60%), followed by P. pinea emulsion (53%). In summary, some of the studied EOs and Hds showed antioxidant and antimicrobial activities and they are possible candidates to address the consumers demand for more sustainable and responsibly sourced ingredients.

Nuts and Metabolic Syndrome: Reducing the Burden of Metabolic Syndrome in Menopause.

Menopause imposes a dramatic fall in estrogens, which is followed by an increase in the proportion of fat. The rising androgen/estrogen ratio along the menopause transition favors the accumulation of central fat, which contributes to insulin resistance and a series of concatenated effects, leading to a higher incidence of metabolic syndrome. The modulatory effect of diet on the metabolic syndrome phenotype has been shown for the Mediterranean diet, and nuts are key determinants of these health benefits. This review of the impact of nuts on the risk factors of the metabolic syndrome cluster examined studies—prioritizing meta-analyses and systemic reviews—to summarize the potential benefits of nut ingestion on the risk of metabolic syndrome associated with menopause. Nuts have a general composition profile that includes macronutrients, with a high proportion of unsaturated fat, bioactive compounds, and fiber. The mechanisms set in motion by nuts have shown different levels of efficacy against the disturbances associated with metabolic syndrome, but a beneficial impact on lipids and carbohydrate metabolism, and a potential, but minimal reduction in blood pressure and fat accumulation have been found.

An Operations Research-Based Approach to the Allocation of COVID-19 Vaccines

The global scientific community has been successful in their efforts to develop, test, and commercialize vaccines for COVID-19. However, the limited supply of these vaccines remains to be a widespread problem as different nations have started their respective vaccine rollouts. Policymakers continue to deal with the difficult task of determining how to allocate them. This research work will present how the use of mathematical models can provide valuable decision support under such conditions. Both a linear programming model and a nonlinear programming model have been developed to determine the optimal allocation of COVID-19 vaccines that minimize fatalities and COVID-19 transmission, respectively. These scenarios have to be dealt with when not enough vaccines are available, and the pandemic is still in progress. The model is capable of handling large scale allocation problems such as those intended for the general population of a country. It could also be scaled down for organizations such as private companies or universities. The model also considers multiple vaccines with different levels of efficacy. The distribution of vaccines reduces transmission and relative infectiousness of individuals across different age groups. A hypothetical case study is solved to illustrate the computational capability of the models. The results indicate that priority should be given to the elderly when fatalities are minimized. In contrast, the younger population should then be prioritized when the objective shifts to suppressing contagion.

Interlaboratory study for the evaluation of three microtiter plate-based biofilm quantification methods

Microtiter plate methods are commonly used for biofilm assessment. However, results obtained with these methods have often been difficult to reproduce. Hence, it is important to obtain a better understanding of the repeatability and reproducibility of these methods. An interlaboratory study was performed in five different laboratories to evaluate the reproducibility and responsiveness of three methods to quantify Staphylococcus aureus biofilm formation in 96-well microtiter plates: crystal violet, resazurin, and plate counts. An inter-lab protocol was developed for the study. The protocol was separated into three steps: biofilm growth, biofilm challenge, biofilm assessment. For control experiments participants performed the growth and assessment steps only. For treatment experiments, all three steps were performed and the efficacy of sodium hypochlorite (NaOCl) in killing S. aureus biofilms was evaluated. In control experiments, on the log10-scale, the reproducibility SD (SR) was 0.44 for crystal violet, 0.53 for resazurin, and 0.92 for the plate counts. In the treatment experiments, plate counts had the best responsiveness to different levels of efficacy and also the best reproducibility with respect to responsiveness (Slope/SR = 1.02), making it the more reliable method to use in an antimicrobial efficacy test. This study showed that the microtiter plate is a versatile and easy-to-use biofilm reactor, which exhibits good repeatability and reproducibility for different types of assessment methods, as long as a suitable experimental design and statistical analysis is applied.

The effect of botulinum toxin injection dose on the appearance of surgical scar

Early postoperative injection of botulinum toxin type A (BTxA) can reduce surgical scar hypertrophy. BTxA injection at different time points is associated with different levels of efficacy, but the efficacy of different doses of BTxA for scar management has not investigated. The purpose of this study was to investigate the effect of different doses of BTxA administered early after surgery on scar improvement through a split-scar experiment. The study included 22 patients who underwent surgery between September 2019 and October 2020. High- and low-dose BTxA was randomly administered into each half of the surgical wound closure immediately after surgery. One half of the incision was injected with a low dose (4 U) of BTxA, and the other half was injected with a high dose (8 U). The scars were then evaluated at postoperative 6 months using the modified Stony Brook Scar Evaluation Scale (mSBSES), and patient satisfaction was evaluated using the Visual Analogue Scale (VAS). The occurrence of complications or adverse events was also recorded. Twenty patients completed the study and were analyzed. Compared with the low-dose sides, the high-dose sides had significantly better mSBSES scores and significantly higher VAS scores (p < 0.01, respectively). No serious adverse reactions or post-injection complications were observed. Immediately after the operation, high-dose BTxA (that is within the therapeutic range) injection improved the appearance of postoperative scar more than low-dose injection.

Private Demand for Covid-19 Vaccine: A Contingent Assessment from a Low-and Middle-income Country.

This study aimed to estimate Iranian willingness to pay (WTP) for a hypothetical COVID-19 vaccine and its determinants. A cross-sectional online survey was conducted from May 2nd to 20th, 2020 among the general population of Iran to estimate WTP for hypothetical COVID-19 vaccines. Four scenarios with different levels of efficacy and duration of protection were presented to respondents in the payment card scale of the contingent valuation method (CVM). With the corresponding WTPs under different scenarios, mean, trimmed mean, median WTP values, and vaccine demand was estimated. A semi-log regression model was employed to identify key factors. The vaccine acceptance rate and positive WTP were about 70% and 80%, respectively. The reluctant individuals believed free vaccination is a government responsibility. The highest trimmed mean and median WTP values were the US $15 and $4 for the vaccine with more than 80% efficacy and one-time vaccination. The median decreased to the US $2 in less effective scenarios. The vaccine demand was price-inelastic. Price, self-assessment virus risk, age, gender, education, income, and working in the health sector were significant factors. Given the price inelasticity of the COVID-19 vaccine, providing free vaccination by the Iranian government is highly recommended, particularly for low-income and vulnerable individuals.

Planning for a Gonococcal Vaccine: A Narrative Review of Vaccine Development and Public Health Implications.

Declining gonococcal susceptibility to ceftriaxone and azithromycin has raised the possibility of untreatable gonorrhea in the future and reignited interest in gonococcal vaccine development. Despite decades of research, previous gonococcal vaccine candidates have been ineffective. A growing body of data suggests that meningococcal group B outer-membrane vaccines may be cross-protective against Neisseria gonorrhoeae. Clinical trials of a licensed vaccine against Neisseria meningitidis serogroup B containing an outer-membrane vaccine component are underway to determine its efficacy against N. gonorrhoeae. Other experimental gonococcal vaccine candidates are in the preclinical phases. Population impact of future gonococcal vaccines with different levels of efficacy and duration of protection in various populations is being evaluated using modeling studies. Despite recent progress, gaps in gonococcal vaccine research remain. Research is needed to evaluate vaccine efficacy in preventing gonococcal infections acquired via various anatomic routes and among patients coinfected with other sexually transmitted infections. Studies that model the impact of a future vaccine on high-burden populations such as men who have sex with men and estimate both vaccine cost-effectiveness and the incremental cost-effectiveness ratio of vaccination to antimicrobial resistance and treatment costs are warranted. This narrative review examines the current state of gonococcal vaccine research, the possible impact of a gonococcal vaccine on gonorrhea rates based on modeling studies, gaps in the gonococcal vaccine literature, and public health implications of a future gonococcal vaccine on reducing the gonorrhea burden in the United States.

The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs.

Unconjugated anti-cancer IgG1 monoclonal antibodies (mAbs) activate antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells and antibody-dependent cellular phagocytosis (ADCP) by macrophages, and these activities are thought to be important mechanisms of action for many of these mAbs in vivo. Several mAbs also activate the classical complement pathway and promote complement-dependent cytotoxicity (CDC), although with very different levels of efficacy, depending on the mAb, the target antigen, and the tumor type. Recent studies have unraveled the various structural factors that define why some IgG1 mAbs are strong mediators of CDC, whereas others are not. The role of complement activation and membrane inhibitors expressed by tumor cells, most notably CD55 and CD59, has also been quite extensively studied, but how much these affect the resistance of tumors in vivo to IgG1 therapeutic mAbs still remains incompletely understood. Recent studies have demonstrated that complement activation has multiple effects beyond target cell lysis, affecting both innate and adaptive immunity mediated by soluble complement fragments, such as C3a and C5a, and by stimulating complement receptors expressed by immune cells, including NK cells, neutrophils, macrophages, T cells, and dendritic cells. Complement activation can enhance ADCC and ADCP and may contribute to the vaccine effect of mAbs. These different aspects of complement are also briefly reviewed in the specific context of FDA-approved therapeutic anti-cancer IgG1 mAbs.

Efficacy of NS5A inhibitors against unusual and potentially difficult-to-treat HCV subtypes commonly found in sub-Saharan Africa and South East Asia

The efficacy of NS5A inhibitors against several less common subtypes of hepatitis C virus (HCV) is poorly characterised. Some subtypes including 3b, 3g, 6u and 6v commonly harbour amino acid residues in NS5A that may confer resistance to direct-acting antivirals (DAAs) in other common subtypes. Data from patients also suggest that 1l and 4r with amino acid substitutions at positions 28-31 and 93 in NS5A are relatively resistant to DAA therapy. In this study, we tested the efficacy of daclatasvir, elbasvir, ledipasvir, pibrentasvir and velpatasvir against these subtypes using the SGR-JFH1 replicon backbone. NS5A inhibitors showed different levels of efficacy with only pibrentasvir effective against all tested subtypes. Daclatasvir and ledipasvir were ineffective against 6u and 6v (half maximal effective concentration [EC50] values of 239-321 nM) while 3b and 3g were only susceptible to pibrentasvir. Analysis of effects of individual mutations indicated that Q30R in 1l increased the EC50 of ledipasvir by 18-fold, conferring intermediate resistance, while those of L31M and Y93H in 4r induced increases in EC50 values of 2,100- and 3,575-fold (high-level resistance). The high ledipasvir EC50 values of 1l with the Q30R substitution, 4r L31M and 4r Y93H may explain the treatment failure in patients who were infected with these viruses and treated with ledipasvir+ sofosbuvir. This study also shows the ineffectiveness of the first generation NS5A inhibitors against 6u and 6v, and confirms the inherent resistance of 3b and 3g to most NS5A inhibitors. Clinical studies to confirm invivo sensitivity to NS5A inhibitors are urgently needed so that rational, effective treatment strategies may be developed for unusual subtypes. Little is known about the efficacy of NS5A inhibitors against some "unusual" hepatitis C virus (HCV) subtypes including 1l, 3b, 3g, 4r, 6u and 6v. In this study, we manufactured HCV replicons which express the NS5A protein from the unusual HCV subtypes 1l, 3b, 3g, 4r, 6u, 6v. We then tested the effect of the NS5A inhibitors daclatasvir, elbasvir, ledipasvir, pibrentasvir and velpatasvir on blocking replication, using these replicons. We show that these replicons are resistant at some level to all NS5A inhibitors other than pibrentasvir.

Double-Stranded RNAs (dsRNAs) as a Sustainable Tool against Gray Mold (Botrytis cinerea) in Grapevine: Effectiveness of Different Application Methods in an Open-Air Environment.

Grapevine is one of the most important and globally widespread fruit species, with a high impact on the economy of many countries but with an intense environmental effect. Therefore, new environmentally friendly defense strategies against fungal pathogens are needed for more sustainable agriculture. A novel emerging approach is spray-induced gene silencing (SIGS), which concerns the exogenous application of double-stranded RNA (dsRNA) inducing enhanced plant resistance against fungal pathogens. Here, we tested the ability of SIGS to prevent and counteract infection of Botrytis cinerea, one of the most economically impacting pathogens of grapevine. In particular, we tested three independent approaches for dsRNA delivery into plants: (i) high pressure spraying of leaves; (ii) petiole adsorption of dsRNAs; (iii) postharvest spraying of bunches. We demonstrated that independently from the method of application, SIGS can reduce virulence of the fungus. Moreover, we also observed three different levels of efficacy depending on the method of application. Thus, the present data provide crucial information on the possibility to exploit SIGS as an alternative sustainable and ecofriendly strategy for grapevine pre- and postharvest protection.

Nicotine replacement therapy: A friend or foe.

According to the World Health Organization (WHO) Framework Convention for Tobacco Control (FCTC), tobacco cessation is a primary health-care service that should be provided not only to the people having adverse habits of consuming tobacco but also to the nonconsumer, as they can also be harmed due to its deleterious effects. Tobacco has been regarded as a potential risk factor for oral diseases such as oral potentially malignant disorders and oral cancers. Various aids of achieving cessation have been studied, including education of the ill effects of tobacco to the patient, behavioral counseling, and pharmacotherapy. Various pharmacological interventions are available nowadays but nicotine replacement therapy (NRT) is most widely used. The various types of NRT products results in general and breakthrough craving relief with immediate release of nicotine. All of these products have different levels of efficacy and variable rates of nicotine absorption. Knowledge of these will be beneficial for the patients, the budding dentist and the nation in the upcoming days ahead.

PCN288 HOW IS METASTATIC MELANOMA TREATED IN THE PUBLIC HEALTH SYSTEM IN BRAZIL?: A CALL FOR CHANGE

- To undertake an exploratory analysis of the patients with metastatic melanoma and the treatment they received at SUS between the years 2015 and 2017. - We evaluated the data available at DATASUS, which were originated from the Ambulatory Chemotherapy Information Systems – SUS (SIASUS). In order to retrieve the data, we used the International Classification of Diseases C43 (the ICD for melanoma) and the period comprised between January 2015 and December 2017. These were then reviewed in order to be correctly assigned to treatment groups related to different levels of efficacy. We excluded those APACs that recorded ICD C43 but were related to supportive medications (such as bisphosphonates for bone metastasis or pain medications). - We initially identified 13.187 APACs related to the treatment of melanoma. Of these, we excluded 2.344, which were related to either some systemic treatment for stage III melanoma or supportive medications. Therefore, we ended up analyzing 10.843 APACs, related to the treatment of metastatic melanoma of 4.338 patients treated between January 2015 and December 2017. We identified 19 different treatment protocols used as first line, of which 11 consisted of single drug and 8 of drug combinations. Over the two-year period (and excluding those who were already on some treatment in January 2015), 3.097 (88%) and 281 (8%) patients initiated treatment with a minimally effective or moderately effective regimen, respectively. Only 0.4% of patients initiated their treatment with an effective therapy. - Based on the analysis of 4.338 patients with metastatic melanoma treated between 2015 and 2017 in the Brazilian public health system, more than 97% of treatments were classified as minimally effective. The median duration of treatment was expectedly short, and the variety of first line therapies was concerningly high. These data are the result of an outdated reimbursement model and the lack of mandatory treatment standard.

IL PRINCIPIO DI NON-REFOULEMENT: CRITICITA' APPLICATIVE

Il principio di non respingimento è uno degli strumenti più rilevanti del diritto internazionale per la protezione dei migranti. Per comprendere l'ampiezza della sua applicazione e i problemi legati al principio di non respingimento, è tuttavia opportuno analizzare le varie categorie di migranti per capire chi può ricevere questa protezione. Questo processo di analisi delle categorie, inoltre, evidenzia la presenza di altre difficoltà nell'attuazione generalizzata delle garanzie per i migranti. Infatti, non tutti i trattati si applicano a tutti i tipi di migranti. Anche la Convenzione di Ginevra sullo status di rifugiato, come dice il nome, si riferisce solo ai rifugiati. In particolare, l'articolo 1 della Convenzione definisce "rifugiato" la persona che "per fondato timore di essere perseguitata per motivi di razza, religione, nazionalità, appartenenza a un determinato gruppo sociale o opinione politica, si trova al di fuori del Paese di cui è cittadino e non può o, a causa di tale timore, non vuole avvalersi della protezione di quel Paese"; Pertanto, le sue protezioni - compresa quella data dal principio di non respingimento, stabilito dall'articolo 33 - garantiscono solo questa specifica categoria di migranti; categoria legata - come già detto - ad una lista chiusa di possibili cause di persecuzione. Altri ostacoli ad un'attuazione armonizzata del principio di non respingimento si trovano anche nelle differenze tra i trattati che lo definiscono. Nella sua prima definizione, nella Convenzione di Ginevra allo status di rifugiato del 1951, il principio vieta agli Stati membri di "espellere o rimpatriare ("refouler") un rifugiato in qualsiasi modo alle frontiere di territori in cui la sua vita o la sua libertà sarebbero minacciate a causa della razza, della religione, della nazionalità, dell'appartenenza a un determinato gruppo sociale o delle opinioni politiche" (Convenzione di Ginevra allo status di rifugiato, art. 33). L'esistenza di varie definizioni e la loro inadeguatezza a modelli migratori reali creano difficoltà nell'attuazione del principio stesso. In questo senso, uno dei maggiori problemi nello scenario attuale è quello dato dall'applicazione del principio agli afflussi massicci. Questo termine si riferisce a quelle migrazioni caratterizzate dall'arrivo su una frontiera internazionale di un gran numero di persone con un ritmo rapido e dall'incapacità dello Stato di accoglienza di rispondere adeguatamente all'arrivo dei migranti (in particolare, le procedure individuali di asilo non sono sufficienti per far fronte all'elevato numero di migranti). Diversi strumenti internazionali forniscono un'ampiezza diversa del campo di applicazione del principio; gli organi di controllo che controllano l'attuazione del principio hanno livelli di efficacia diversi. L'incertezza è ancora più ampia in considerazione dei nuovi movimenti migratori, come gli afflussi massicci; gli Stati approfittano quindi di questa situazione per non applicare il principio di non respingimento e l'altra protezione per i migranti. Detto questo, è impellente raggiungere una visione dottrinale più condivisa su questo tema, al fine di cooperare con la giurisprudenza per stimolare gli Stati verso una maggiore protezione dei migranti.