Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials.

BACKGROUND: During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. METHODS: A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. RESULTS: The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. CONCLUSIONS: This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients.

Different peripheral expression patterns of the nicotinic acetylcholine receptor in dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and peripheral immune cells points out their involvement in several pathological conditions. Indeed, the deregulated function of the nAChR was previously correlated with cognitive decline and neuropsychiatric symptoms in Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). The evaluation in peripheral immune cells of nAChR subtypes, which could reflect their expression in brain regions, is a prominent investigation area. OBJECTIVES: This study aims to evaluate the expression levels of both the nAChR subunits and the main known inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with DLB and AD to better characterize their involvement in these two diseases. RESULTS: Higher gene expression levels of TNFα, IL6 and IL1ß were observed in DLB and AD patients in comparison with healthy controls (HC). In our cohort, a reduction of nAChRα4, nAChRß2 and nAChRß4 was detected in both DLB and AD with respect to HC. Considering nAChR gene expressions in DLB and AD, significant differences were observed for nAChRα3, nAChRα4, nAChRß2 and nAChRß4 between the two groups. Moreover, the acetylcholine esterase (AChE) gene expression was significantly higher in DLB than in AD. Correlation analysis points out the relation between different nAChR subtype expressions in DLB (nAChRß2 vs nAChRα3; nAChRα4 vs nAChRα3) and AD (nAChRα4 vs nAChRα3; nAChRα4 vs nAChRß4; nAChRα7 vs nAChRα3; nAChRα7 vs nAChRα4). CONCLUSIONS: Different gene expressions of both pro-inflammatory cytokines and nAChR subtypes may represent a peripheral link between inflammation and neurodegeneration. Inflammatory cytokines and different nAChRs should be valid and accurate peripheral markers for the clinical diagnosis of DLB and AD. However, although nAChRs show a great biological role in the regulation of inflammation, no significant correlation was detected between nAChR subtypes and the examined cytokines in our cohort of patients.

Serum tryptase levels in patients with psoriasis: a pilot study for a possible useful biomarker.

In psoriasis, biomarkers for disease prognosis and response to treatment may help clinicians to improve patient management. Hence, we decided to evaluate the role of serum tryptase (ST) in a sample of patients with psoriasis. We found higher levels of ST in patients with scalp psoriasis than in those without (6.1 vs. 4.6 ng/mL), in those with palmoplantar psoriasis than in those without (5.3 vs. 5 ng/mL) and, with less significance, in those with psoriatic arthritis than in those without (6.1 vs. 5.1 ng/mL).

Successful use of dupilumab for the treatment of atopic dermatitis on the genitals, a neglected anatomical site.

Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.

Biological insight into the extracellular vesicles in women with and without gestational diabetes.

PURPOSE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles (EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy. METHODS: We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry. RESULTS: The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (p = 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (p = 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs. CONCLUSIONS: These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM.

Vipera snakebite in Europe: a systematic review of a neglected disease.

In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles about snakebites and their management, despite the fact that dermatologists, especially from rural hospitals, can be called into the emergency room to consult the management of suspected snakebites. In this systematic review, we highlighted the main clinical and laboratory aspects of snakebites from Vipera spp. in Europe, by reviewing 3574 studies initially retrieved from PubMed, Embase and Cochrane CENTRAL databases. Of these, 78 were finally included in the systematic review. We found that the most involved taxon was V. berus in 63.3% and the most involved anatomic site of the bite was the upper limbs 53.1% with fang marks reported in 90.5%. The mean age of the patients was 32.9 years, and bites were slightly more common among males (58.2%). A wound washing was performed in 86.9% of cases before the hospitalization. The most frequently reported grade of envenomation was G2 (42.2%). In addition to local dermatological symptoms (extended erythema, oedema, cutaneous necrosis, hives, purpura, petechiae, acute compartment syndrome), numerous systemic symptoms have also been reported, including fatigue (14.4%), pain (75.3%), fever (49.2%), direct anaphylactoid reaction (5.3%), anxiety (60.8%), cranial nerve neurotoxicity (14.8%), dysesthesia/paraesthesia (7.9%), vomiting (33.7%), abdominal pain (23.3%), diarrhoea (15.4%), dyspnoea (6.3%), proteinuria (10.6%) and haematuria (9.3%). Secondary infections were present in 3.5% and disseminated intravascular coagulation in 3.1% of cases, and fasciotomy was performed in 4.2% cases, while an amputation in 6.9%. Only 0.9% of patients died. Antivenom was administered in 3053 cases. In conclusion, there is a pressing need for robust multi-centre randomized control trials, standardized protocol for snakebite management and antivenom administration across Europe and a National snakebite register for each European country.

Circulating CD40 ligand, Dickkopf-1 and P-selectin in HIV-infected patients.

OBJECTIVES: The aim of this study was to evaluate the circulating levels of CD40 ligand (CD40 L), Dickkopf-1 (DKK-1) and P-selectin, their relationships and their contributions to cardiovascular risk in subjects with HIV infection. METHODS: The study population included 80 HIV-infected patients, 14 (17.5%) of whom had diabetes mellitus (DM) and 32 (40.0%) of whom had arterial hypertension (AH). The HIV-infected patients were compared with a control group with similar demographic and clinical features. CD40L, DKK-1 and P-selectin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The HIV-infected patients showed higher levels of all the cardiovascular disease (CVD) markers. Both serum CD40L and DKK-1 were significantly higher in HIV-infected patients than in the HIV-negative controls (P < 0.001), while soluble P-selectin showed no significant between-group difference (P = 0.133), reflecting the role of HIV infection in CVD. In the HIV-infected group, patients with DM showed lower levels of CD40L and DKK-1 in comparison with the nondiabetic patients and patients with AH (P < 0.05, with Bonferroni correction). In contrast, patients with AH showed higher levels of CD40L and DKK-1 in comparison to patients without DM or AH (P < 0.05, with Bonferroni correction). Patients with AH showed higher levels of CD40L and DKK-1 than patients with DM (P < 0.05, with Bonferroni correction). CONCLUSIONS: In this study, we found that HIV-infected patients displayed significantly higher circulating levels of both CD40L and DKK-1, which were linearly and directly correlated, when compared to HIV-negative patients. The presence of diabetes was associated with lower levels of both CD40L and DKK-1, whereas the presence of hypertension was associated with higher levels of CD40L.

High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study.

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

Twenty-four hour hyperinsulinemic-euglycemic clamp improves postoperative nitrogen balance only in low insulin sensitivity patients following cardiac surgery.

BACKGROUND: Critically ill patients often suffer from a protein catabolic state. The aim of this study was to demonstrate that nitrogen balance (NB) in cardiac patients admitted to the intensive care unit (ICU) is related to their insulin sensitivity level and that supraphysiologic doses of insulin can restore anabolism. MATERIALS AND METHODS: Twenty-eight patients that were admitted to ICU in enteral and/or parenteral nutrition have been enrolled in this study. All patients received a standard nutrition protocol for at least 3 days before starting the study. These patients received either enteral or parenteral nutrition based on 1.4 kcal/kg/h and 1.1 g/kg/24 h of proteins. Participants were studied for three 24 h periods (P1 , P2 , and P3 ). Twenty-four hour NB was calculated from urinary urea nitrogen excretion, fixed protein and energy intake during each of the three periods (P1 , P2 , and P3 ). Simultaneous to P2, a 24 h hyperinsulinemic-euglycemic clamp (HEC) was performed to determine patients' insulin sensitivity (IS) or insulin resistance (IR), as well as the impact of high doses of insulin on NB. RESULTS: Nitrogen balance remained consistently positive in the IS group regardless of the clamp. In IR patients, NB was negative before the clamp and became positive during P2 and P3 . Insulin sensitivity improved during the HEC in IR patients (P < 0.001). CONCLUSIONS: A negative NB was found only in insulin resistant patients admitted to the ICU for more than 7 days. A 24-h period HEC improved NB in these patients.

Mole modifications following controlled ovarian stimulation for assisted reproduction technologies.

BACKGROUND: The role of estrogens on moles biology remains undefined although estrogenic receptors have been found on melanocytes. It has been postulated that supraphysiological estrogen levels could promote the progression of moles to melanoma. Women undergoing controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) are exposed to high levels of estrogens, produced by the ovary in response to exogenous gonadotropin administration. The aim of this study is to assess whether COS for ART may have an impact on mole structure and/or characteristics. METHODS: Women undergoing to ART for various infertility conditions were included in the study. Personal and clinical data were collected. Dermatoscopic features and scores (total dermoscopy score--TDS) were statistically compared before COS and after a 6-month follow-up period. Statistical correlation was performed between estradiol, FSH blood levels and relative variation in moles dimensions. RESULTS: A total of 46 patients were included in the study. One hundred and seventy-five melanocytic lesions from 31 patients were evaluated at both time points. Although statistically significant differences were found in mole dimension and TDS between the two time points, these differences had no relevance in the clinical setting not suggesting the need for mole excision. Moreover, the only statistically significant correlation with estradiol blood concentration on hCG administration day was found with one-axis dimensional variation. CONCLUSIONS: To our knowledge this is the first work to evaluate the effect of COS on moles. The obtained results do not support a causal relation between the supraphysiological hormone levels stimulation and worsening of clinical and dermoscopical features of moles. Further study is needed to clarify whether estrogens plays a role in melanoma.

Uterine endometrioid carcinoma with focal area of choriocarcinomatous differentiation: case report.

PURPOSE OF INVESTIGATION: An endometrioid carcinoma coexisting with choriocarcinomatous differentiation is an uncommon event with an aggressive clinical course and a poor prognosis. MATERIALS AND METHODS: The authors describe an endometrioid carcinoma of the endometrium provided with a focus of choriocarcinoma-like cells in a 50-year-old menstruated woman with a history of abnormal uterine bleeding. A total bilateral hystero-annessectomy was performed. RESULTS: Histopathologic study showed endometrioid adenocarcinoma limited to the endometrium with a single microinvasive (< one mm) choriocarcinomatous focus. Immunohistochemistry established intense reactivity of tumor cells for CK 7 and AE1/AE3, for beta-human chorionic gonadotropin (beta-hCG), and for HER2 confirming the diagnosis. During the clinical course and follow-up, serum levels of beta-hCG were always negative. Up to date the patient is still alive with no evidence of disease. CONCLUSION: Even if endometrioid carcinoma with choriocarcinomatous differentiation is considered highly malignant, occasionally it may have a good prognosis, especially when a non-invasive behaviour is detected together with negative serum beta-hCG levels.

Impact of surgery and radiotherapy in women with uterine malignancies.

According to the National Health and Social Life Survey, sexual dysfunction affects about 43% of perimenopausal women. A diagnosis of cancer has a profound physical, emotional, and social impact, influencing the relationship with the body, the perception of illness and death, family, social and professional relationships, and the relationship with the partner and, consequently, sexuality. Loss of desire, dyspareunia, orgasmic disorder, difficulties in emotional and physical closeness to the partner, feelings of shame, and inadequacy commonly occur after treatment for uterine cancer; however, if these problems are associated with surgery or with radiotherapy, still remains unclear. According to this study, the authors may conclude that the experience of cancer could lead patients to a rediscovery of. their own sexuality and to an improvement in the relationship with their partner, showing that, sometimes, the relational and psychological factors assume greater importance than physical effects on sexuality, and they can somewhere compensate the morphofunctional failure.

Sonoelastography as method for preliminary evaluation of uterine cervix to predict success of induction of labor.

INTRODUCTION: Induction of labor is a useful practice to solve many obstetric situations but has a large impact on the health of women and their babies and therefore needs to be clearly justified clinically. AIM: To determine the sensitivity of sonoelastography in the evaluation of the cervix to predict the success of induction. MATERIALS AND METHODS: We enrolled 53 subjects preparing for induction of labor. Transvaginal evaluation of cervical length and a sonoelastogram were performed. We preliminarily classified the sonoelastograms into five elastography index (EI) categories and examined the different distribution of cesarean or spontaneous deliveries in various subgroups of EI by χ(2) test and multivariate analysis by logistic regression. RESULTS: Statistical analysis revealed a significant difference of prevalence of spontaneous delivery (EI1-3 82.75%, EI4-5 45.8%) versus cesarean section (EI1-3 17.25%, EI4-5 54.16%) (p = 0.0072). The diagnostic validity of EI was evaluated using the receiver operating characteristic curve and cut-off of the predictive value was EI3. DISCUSSION: The results of our study indicate that sonoelastography is an innovative technique that could allow a more objective preliminary evaluation of the cervix before inducing labor, however further studies with a larger number of subjects and a standardization of image acquisition are necessary.

Effectiveness of vortioxetine in elderly patients with major depressive disorder in real-world clinical practice: Results from the RELIEVE study.

BACKGROUND: Data demonstrating the real-world, long-term effectiveness of vortioxetine in elderly patients with major depressive disorder (MDD) are clinically useful to confirm findings from randomized trials. METHODS: RELIEVE was a multinational, 24-week, observational, prospective study in outpatients with MDD initiating vortioxetine treatment in routine care settings (NCT03555136). Here, we report data from a subgroup of 130 patients aged ⩾ 65 years. The primary study outcome was changed from baseline in patient functioning assessed using the Sheehan Disability Scale (SDS). Other clinical outcomes included depression severity (Patient Health Questionnaire-9 [PHQ-9] and Clinical Global Impressions-Severity [CGI-S]), cognitive performance (Digit Symbol Substitution Test [DSST]) and symptoms (Perceived Deficits Questionnaire - Depression-5 item [PDQ-D-5]), and health-related quality of life (HRQoL) (EuroQoL 5 Dimensions 5 Levels [EQ-5D-5L]). RESULTS: Clinically meaningful and statistically significant improvements in patient functioning, depressive symptoms, cognitive function, and HRQoL were observed at week 24. Least squares mean SDS, PHQ-9, CGI-S, PDQ-D-5, DSST, and EQ-5D-5L scores improved from baseline by 6.5, 5.7, 1.2, 3.2, 4.4, and 0.11 points, respectively (p < 0.01 for all). Adverse events were observed in 23.1% of patients. CONCLUSIONS: Consistent with previous clinical studies of vortioxetine, this study supports the effectiveness and safety of vortioxetine in treating elderly patients with MDD in a real-world setting over a 6-month period. Patients showed clinically relevant and sustained improvements in psychosocial functioning, depressive symptoms, and cognitive function after receiving vortioxetine, which was generally well tolerated. Main study limitations include the open-label study design and lack of a placebo or comparator group.

Melanin-based color variation in response to changing climates in snakes.

Melanism, the process of heavier melanin deposition, can interact with climate variation at both micro and macro scales, ultimately influencing color evolution in organisms. While the ecological processes regulating melanin production in relation to climate have been extensively studied, intraspecific variations of melanism are seldom considered. Such scientific gap hampers our understanding of how species adapt to rapidly changing climates. For example, dark coloration may lead to higher heat absorption and be advantageous in cool climates, but also in hot environments as a UV or antimicrobial protection mechanism. To disentangle such opposing predictions, here we examined the effect of climate on shaping melanism variation in 150 barred grass snakes (Natrix helvetica) and 383 green whip snakes (Hierophis viridiflavus) across Italy. By utilizing melanistic morphs (charcoal and picturata in N. helvetica, charcoal and abundistic in H. viridiflavus) and compiling observations from 2002 to 2021, we predicted that charcoal morphs in H. viridiflavus would optimize heat absorption in cold environments, while offering protection from excessive UV radiation in N. helvetica within warm habitats; whereas picturata and abundistic morphs would thrive in humid environments, which naturally have a denser vegetation and wetter substrates producing darker ambient light, thus providing concealment advantages. While picturata and abundistic morphs did not align with our initial humidity expectations, the charcoal morph in N. helvetica is associated with UV environments, suggesting protection mechanisms against damaging solar radiation. H. viridiflavus is associated with high precipitations, which might offer antimicrobial protection. Overall, our results provide insights into the correlations between melanin-based color morphs and climate variables in snake populations. While suggestive of potential adaptive responses, future research should delve deeper into the underlying mechanisms regulating this relationship.

Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Iloprost treatment summer-suspension: effects on skin thermal properties and cytokine profile in systemic sclerosis patients.

AIM: Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc). METHODS: Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period. RESULTS: Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension. CONCLUSION: Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.

Quasi-SMILES: Self-consistent models for toxicity of organic chemicals to tadpoles.

Simplified molecular input-line entry systems (SMILES) are the representation of the molecular structure that can be used to establish quantitative structure-property/activity relationships (QSPRs/QSARs) for various endpoints expressed as mathematical functions of the molecular architecture. Quasi-SMILES is extending the traditional SMILES by means of additional symbols that reflect experimental conditions. Using the quasi-SMILES models of toxicity to tadpoles gives the possibility to build up models by taking into account the time of exposure. Toxic effects of experimental situations expressed via 188 quasi-SMILES (the negative logarithm of molar concentrations which lead to lethal 50% tadpoles effected during 12 h, 24 h, 48 h, 72 h, and 96 h) were modelled with good results (the average determination coefficient for the validation sets is about 0.97). In this way, we developed new models for this amphibian endpoint, which is poorly studied.