Psychological Distress in Women With Abnormal Pap Smear Results Attending Cervical Cancer Screening.

OBJECTIVE: Women often experience psychological distress upon receipt of an abnormal Pap test result. This study aimed to evaluate psychological distress and its correlates among women who received an abnormal Pap screening test result. MATERIAL AND METHODS: A cross-sectional study was performed in a cohort of 172 consecutive women who had attended screening for cervical cancer and who received abnormal Pap smear results and underwent additional diagnostic procedures (colposcopy/biopsy/endocervical curettage). The participants filled out a questionnaire on sociodemographic variables and the Cervical Dysplasia Distress Questionnaire. Multivariate linear regression was used for the analysis of the data. For multiple comparisons, the Bonferroni correction was applied to adjust the level of significance. RESULTS: In women who received an abnormal Pap smear result, the independent correlate of higher psychological distress (by Cervical Dysplasia Distress Questionnaire score) before diagnostic procedures was lower satisfaction with information/support received from other people ( p = .002). Correlates of psychological distress in women older than 40 years with abnormal Pap smear were anxiety ( p = .042) and worry about having cervical cancer, general health and having sex ( p = .044). CONCLUSIONS: The authors' findings could enable control of factors predictive of psychological distress in women who received a positive Pap smear screening test before undergoing diagnostic procedures, primarily via active provision of targeted information.

Predictors of depressive symptoms before and after diagnostic procedures in women with abnormal Pap smear attending cervical cancer screening programme in Serbia.

OBJECTIVES: Receipt of a positive Papanicolaou screening result and subsequent referral for diagnostic tests can cause psychological stress. Still, not enough is known about depression before and after the diagnostic test in these women. The aim of this study was to determine the burden and predictors of depressive symptoms prior to and after diagnostic investigations in women who had received a positive Papanicolaou screening result. METHODS: This was a cross-sectional study. Study cohort comprised women who received an abnormal Papanicolaou screening result. Women completed the socio-demographic questionnaire and 'The Center for Epidemiologic Studies Depression, CES-D' questionnaire before and after diagnostic tests (colposcopy/biopsy/endocervical curettage) to assess factors related to depression. RESULTS: No significant difference was noted in the frequency of depressive symptoms (CES-D score ≥ 16) before and after diagnostic investigations, but the mean score on CES-D scale showed a significant difference before and after diagnostic investigations (13.98 ± 9.56 and 12.74 ± 9.15, respectively). A significant predictor of depression before diagnostic investigations was spontaneous abortion, whereas family history of other gynaecological cancers was a predictor of depression after diagnostic investigations. CONCLUSIONS: Our findings could contribute to improving the rates of cervical cancer screening, by identifying women at risk for depression before and after investigations.

Predictors of Anxiety Before and After Diagnostic Procedures in Women with Abnormal Papanicolaou Smear in Cervical Cancer Screening Program.

Anxiety is one of the most common causes of withdrawal from follow-up among women with abnormal Papanicolaou screening results. The purpose of this study was to investigate predictors of anxiety in women with abnormal Papanicolaou smear in cervical cancer screening program. A population-based, cross-sectional study concerning the factors related to anxiety was carried out during 2017 in a cohort of women (N = 172) with positive Papanicolaou screening test before and after diagnostic procedures (colposcopy/biopsy/endocervical curettage) at one university Clinical Center in Serbia. Women completed a socio-demographic questionnaire and scale concerning anxiety (Hospital Anxiety and Depression Scale, subscale HADS-Anxiety) immediately before and 2-4 weeks after the diagnostic procedures. Multivariate logistic regression was applied in the data analysis. In our study, 35.2% (n = 52) of women had abnormal anxiety scores before the diagnostic procedures and 40.1% (n = 69) after the diagnostic procedures. Predictors of anxiety before diagnostic procedures were family history of noncervical gynecological cancers, higher level of worry and high burden of depressive symptoms. Significant independent predictors of anxiety after diagnostic procedures in women were rural residence, tension and discomfort during medical procedures, and less satisfaction with information/support. Although there was no significant difference in the prevalence of anxiety before and after diagnostic procedures in women with abnormal Papanicolaou screening results, results of this research will enable doctors to successfully make decisions concerning timely psychological support for women with positive screening test for cervical cancer that is necessary to decrease anxiety in our population.

Internal consistency and validity of the Hospital Anxiety and Depression Scale (HADS) in women with abnormal Pap smear in Serbia.

Receiving a report of an abnormal finding of Pap screening test in women often leads to anxiety and depression. The purpose of this study was to investigate the construct validity and internal consistency reliability of the Serbian version of the Hospital Anxiety and Depression Scale (HADS) in women with abnormal Pap smear results. In 2017, a cross-sectional study was done involving 142 consecutive women attending cervical cancer screening who had received abnormal Pap smear results at one University clinical center in Serbia. We used exploratory factor analysis to establish the structure of the HADS and Cronbach's alpha coefficient was used for assessing the internal consistency. In our study, the HADS demonstrated high internal consistency, for both subscales (Cronbach's alpha coefficient for subscale Anxiety was 0.862, and for subscale Depression was 0.851). The intra-class correlation coefficients for the two components were significant (0.860 and 0.843, p < .001). Principal component analysis with Oblimin rotation indicated a two-factor structure that explained 56.4% of variance. In conclusion, the Serbian version of the HADS showed satisfactory internal consistency reliability and construct validity and could be useful as a screening questionnaire for the assessment of anxiety and depression among women with abnormal Pap smear results.

Reliability and validity of the Center for Epidemiologic Studies Depression (CES-D) scale in Serbian women with abnormal Papanicolaou smear results.

OBJECTIVES: Cervical cancer ranks as the second most frequent cancer among women in Serbia. Organized screening for detection of cervical cancer was introduced in Serbia in 2013 and provided free of charge in all state health facilities. Studies have shown that depression frequently follows the notification of abnormal findings on the Papanicolaou (Pap) screening test. The aim of this study was to examine the reliability and validity of the Center for Epidemiologic Studies Depression (CES-D) scale among women in Serbia receiving a report of abnormal cytology. METHODS: This population-based study used cross-sectional, self-reported data involving 198 consecutive women attending cervical cancer screening who had received abnormal Pap smear results. All participants completed the socio-demographic questionnaire and CES-D scale. Reliability of the CES-D scale was assessed by internal consistency reliability (measured with standardized Cronbach's coefficient α). Exploratory factor analysis was done using Promax rotation. RESULTS: The overall Cronbach's α coefficient of the CES-D scale was 0.865, while the Cronbach's α coefficients for the subscales Depressed affect, Somatic complaints, Positive affect, and Interpersonal relationship were 0.885, 0.802, 0.851, and 0.593, respectively. Principal component analysis with Oblimin rotation indicated four main components that explained 62.0% of variance. Over one-quarter (28.8%) of the participants scored above the cut point (≥16) on the CES-D scale. The mean score for depressive symptoms was 13.0 for the study sample. CONCLUSIONS: The Serbian version of the CES-D scale proved to be a valid and reliable instrument for identifying patients with depressive symptoms among women with abnormal Pap smear results.

Estradiol decreases blood pressure in association with redox regulation in preeclampsia.

In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2-), and peroxynitrite (ONOO-) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2- and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2- as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.-, H2O2, NO2-, and ONOO- in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2-, H2O2, and ONOO- was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.

Could alexithymia predict suicide attempts - a study of Croatian war veterans with post-traumatic stress disorder.

BACKGROUND: To investigate the possibility if alexithymia could be used as a predictor of attempted suicide among patients suffering from post-traumatic stress disorder. SUBJECTS AND METHODS: The study was based on 127 veterans from the 1991-1995 war in Croatia. All the patients involved in this study were previously diagnosed with PTSD. The questionnaires (socio-demographic questionnaire, Mississippi scale for combat related PTSD questionnaire, and 20-item Toronto Alexithymia Scale questionnaire) were administered by investigators. RESULTS: The results suggest that alexithymia was significantly associated with attempted suicide (P=0.020). Furthermore, alexithymia remained a significant predictor of an attempted suicide even in the multivariate regression model, which yielded an odds ratio (OR) of 2.87 (95% confidence intervals 1.18-7.00). CONCLUSIONS: These results point out that alexithymia can be considered as a potential risk factor for suicide in this population, suggesting that it may also be used as an indicator of worsening psychological status and attempted suicide in other population groups with higher alexithymia prevalence.

Depression before and after diagnostic procedures among women with abnormal finding of Papanicolaou screening test.

BACKGROUND: Some studies did find significant differences in the level of depression of women while undergoing diagnostic evaluation of an abnormal Papanicolaou screening smear, but findings were not consistent. This study aimed to assess prevalence and correlates of depression in women with abnormal cervical screening results before and after diagnostic procedures. METHODS: A cross-sectional study was carried out during 2017 in a cohort of women with positive Papanicolaou screening test before and after diagnostic procedures (colposcopy/biopsy/endocervical curettage) at the university Clinical Centre Kragujevac, Serbia. Women completed a questionnaire about demographics, lifestyle, and other factors of interest. Also, questionnaire "Hospital Anxiety and Depression Scale" (HADS) was used immediately before and 2-4 weeks after the diagnostic procedures: a score of ≥8 on HADS-D and HADS-A subscales indicated depression and anxiety, respectively. Multivariate logistic regression was applied in the data analysis. RESULTS: The study comprised 172 women, giving a response rate of 72.3%. The mean age of the participants was 47.8 ± 11.1 years (range 23-65). The frequency of depressive symptoms was significantly higher after diagnostic procedures (48.3%) than before diagnostic procedures (37.2%) (p = 0.038). Before diagnostic procedures, older age (OR = 1.60; 95% CI = 1.09-2.34; p = 0.017), and level of anxiety according to the HADS-A subscale (OR = 1.61; 95% CI = 1.38-1.88; p < 0.001) were significant independent predictors of depression. After diagnostic procedures, significant independent predictors of depression were urban place of residence (OR = 0.12; 95% CI = 0.03-0.47; p = 0.002) and level of anxiety according to the HADS-A subscale (OR = 1.85; 95% CI = 1.54-2.21; p < 0.001). CONCLUSION: Our study showed that older age, rural residence, and anxiety play a role in shaping the risk of depression among women undergoing additional diagnostic procedures after receiving an abnormal Papanicolaou screening result.

Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate-Severe Atopic Dermatitis.

Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate-severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate-severe AD; and NCT03864627: n = 76 adults with moderate-severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1-10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2-4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

Panic Disorder as Unthinkable Emotions: Alexithymia in Panic Disorder, a Croatian Cross-Sectional Study.

OBJECTIVES: Previous research on alexithymia has led to controversy over its prevalence in panic disorder. The aim of this study was to assess the difference in the prevalence of alexithymia in panic disorder and other anxiety disorders. DESIGN AND METHODS: We performed a cross-sectional study on a sample of 71 patients diagnosed with panic disorder and 113 patients diagnosed with other anxiety disorders; both groups were 18-50 years old. Primary outcome was the 20-item Toronto Alexithymia Scale (TAS) score. Secondary outcome was the prevalence of alexithymia defined as a TAS score ≥61. RESULTS: Patients diagnosed with panic disorder had a 25% higher score on the TAS subscale of difficulty identifying feelings than patients diagnosed with other anxiety disorders. The prevalence of alexithymia was 27% in patients with panic disorder and 13% in patients with other anxiety disorders. Patients diagnosed with panic disorder had significantly higher odds for alexithymia. CONCLUSIONS: The results of our study support the hypothesis of higher prevalence of alexithymia in individuals with panic disorder than in individuals with other anxiety disorders. In addition, difficulty identifying feelings as a salient feature of alexithymia is higher in panic disorder than in other anxiety disorders.

Drug-drug interactions in patients receiving hematopoietic stem cell transplantation.

INTRODUCTION: Recipients of hematopoietic stem cell transplantation (HSCT) are exposed to numerous drugs in both pre- and post-transplantation period, which creates an opportunity for drug-drug interactions (DDIs); if clinically relevant DDIs happen, the risk of adverse treatment outcomes is increased. Areas covered: This review is focused on DDIs in recipients of HSCT that were observed and published as clinical trials, case series or case reports. Relevant publications were found by the systematic search of the following online databases: MEDLINE, SCOPUS, EBSCO, and SCINDEX. Expert opinion: The most important DDIs involve cytostatic or immunosuppressant drug on one side, and antimicrobial drugs on the other. The majority of clinically relevant interactions have pharmacokinetic character, involving drug metabolizing enzymes in the liver. Antifungal azoles inhibit metabolism of many cytostatic and immunosuppressant drugs at cytochromes and increase their plasma concentrations. Macrolide antibiotics and fluoroqunolones should be avoided in HSCT recipients, as they have much larger potential for DDIs than other antibiotic groups. HSCT recipients increasingly receive new immunomodulating drugs, and further observational studies are needed to reveal unsuspected DDIs with clinical relevance.

Psychological distress among women with abnormal pap smear results in Serbia: Validity and reliability of the Cervical Dysplasia Distress Questionnaire.

BACKGROUND: Receiving report of an abnormal finding from a Pap screening test in women often leads to psychological distress. OBJECTIVES: The purpose of this study was to assess the reliability and validity of the Cervical Dysplasia Distress Questionnaire (CDDQ) among women in Serbia. METHODS: In 2017, we conducted a cross-sectional study involving 154 consecutive women attending cervical cancer screening who had received abnormal Pap smear results. RESULTS: Reliability assessment showed good internal consistency for all CDDQ subscales (Tension and discomfort: Cronbach's α = 0.844; Embarrassment: α = 0.864; Sexual and reproductive consequences: α = 0.867; and Health consequences: α = 0.913). The test-retest reliability showed that the correlation coefficients (between 0.805 and 0.983) were significant at the 0.01 level for all of the Serbian CDDQ subscales. Principal Axis Factoring with Direct Oblimin rotation indicated four main components that explain 55.0% of variance. CONCLUSION: The Serbian version of the CDDQ scale is a valid and reliable instrument for the assessment of psychological distress among women with abnormal Pap smear results.

Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54.

Objective: To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade®; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX. Methods: REFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30-54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated. Results: During TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups. Conclusions: The similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30. Trial registration number: NCT02222493.

Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study.

BACKGROUND: Sandoz etanercept (SDZ ETN; GP2015) is an etanercept biosimilar with equivalent efficacy and comparable safety and immunogenicity to reference etanercept (ETN) in patients with moderate-to-severe chronic plaque-type psoriasis. METHODS: EQUIRA was a phase III, double-blind study conducted in patients with moderate-to-severe rheumatoid arthritis and inadequate response to disease-modifying anti-rheumatic drugs. Eligible patients were randomized 1:1 to receive subcutaneous 50 mg SDZ ETN or ETN, once-weekly, for 24 weeks. At week 24, patients with at least moderate EULAR response in the SDZ ETN group continued SDZ ETN treatment, and those in the ETN group were switched to receive 50 mg SDZ ETN, for up to 48 weeks. Patients received concomitant methotrexate at a stable dose (10-25 mg/week) and folic acid (≥ 5 mg/week). Equivalence between SDZ ETN and ETN for change from baseline in disease activity score including 28 joint count C-reactive protein (DAS28-CRP) at week 24 (primary endpoint) and comparable safety and immunogenicity profile of SDZ ETN and ETN have previously been demonstrated at week 24. Herein, we present the 48-week results of the study after a single switch from ETN to its biosimilar at week 24. RESULTS: The least squares mean (standard error) change in DAS28-CRP from baseline up to week 48 was comparable between "continued SDZ ETN" (- 2.90 [0.12], n = 148) and "switched to SDZ ETN" (- 2.78 [0.13], n = 131) groups. The proportion of patients achieving EULAR good/moderate responses based on DAS28-erythrocyte sedimentation rate and ACR20/50/70 response rates were comparable between the two groups. The proportion of patients with at least one treatment-emergent adverse event was 42.9% in the "continued SDZ ETN" and 38.0% in the "switched to SDZ ETN" groups. Serious adverse events occurred in 4 patients in each of the two groups. After week 24, none of the patients in the switched group developed anti-drug antibodies (ADAs), while 4 patients in the continued SDZ ETN group had single-event, very low titer, non-neutralizing ADAs detected. CONCLUSIONS: The 48-week results from the EQUIRA study demonstrate that switch from ETN to SDZ ETN in patients with moderate-to-severe rheumatoid arthritis does not impact the efficacy, safety, or immunogenicity of etanercept. TRIAL REGISTRATION: EudraCT number 2012-002009-23 , Registered 19 April 2012-prospectively registered.

Oxidative stress and changes in antioxidative defense system in erythrocytes of preeclampsia in women.

The present study was designed to investigate whether oxidative stress occurred to erythrocytes in preeclampsia and was related to disease. Indicative markers of oxidative stress and changes in antioxidant defense system were assayed in the erythrocytes of 22 healthy pregnant and 20 women with preeclampsia. Results of our work indicated high concentration of hydrogen peroxide, nitrite, peroxynitrite and lipid peroxides in preeclampsia compared to healthy pregnant women. Concentration of superoxide anion was lower in preeclamptic women. There were no differences in concentrations of vitamin E, reduced glutathione and oxidized glutathione. Activity of glutathione-S-transferase (GST) was higher while activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were lower in preeclamptic women. There were no differences in glutathione peroxidase (GSH-Px) activity between the two investigated groups. These results suggest that preeclampsia was characterized by oxidative stress and alteration of antioxidative defense system by disbalance in oxidative/antioxidative status of erythrocytes.

Investigational cannabinoids in seizure disorders, what have we learned thus far?

INTRODUCTION: The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid. AREAS COVERED: In this review, the authors look at the results of preclinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR, and SCINDEX databases. EXPERT OPINION: Preclinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy-resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.

Risk factors for potential drug-drug interactions in intensive care unit patients.

PURPOSE: To determine risk factors for each severity-based category of potential drug-drug interactions (DDIs) encountered at intensive care unit (ICU) patients. METHODS: This was a retrospective cohort analysis of patients treated at the ICU of the Clinical Center Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Three interaction checkers were used to reveal drug-drug interactions: Medscape, Epocrates and Micromedex. RESULTS: The study included 201 patients, 66.19±16.11 years of age. Average number of DDIs per patient ranged from 10.49±8.80 (Micromedex) to 29.43±21.51 (Medscape). Antiarrhythmic or anticonvulsant drug prescription, Charlson Comorbidity Index, male sex, length of hospitalization, number of drugs or therapeutic groups prescribed and surgery increased the risk of DDIs in ICU patients, while presence of delirium or dementia and transfer from emergency department to ICU protected against. CONCLUSIONS: The rate of the DDIs in ICU patients at a tertiary care hospital is high, and adversely influenced by number of drugs or drug groups prescribed per patient, antiarrhythmic or anticonvulsant drug prescription, comorbidities, length of hospitalization and surgery. On the other hand, presence of cognitive deficit and transfer from emergency department to ICU protect ICU patients from the DDIs.

Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study.

OBJECTIVES: To demonstrate the equivalent efficacy and compare the safety and immunogenicity of an etanercept biosimilar, GP2015, with reference etanercept (ETN) in patients with moderate-to-severe, active rheumatoid arthritis (RA), characterised by an inadequate response to synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: In the EQUIRA study, eligible patients (n=376) were randomised 1: 1 to 50 mg GP2015 or ETN subcutaneously, once weekly, for 24 weeks (treatment period 1). Patients from both groups, with at least moderate European League Against Rheumatism response at week 24, received GP2015 up to week 48 (treatment period 2). All patients continued to receive concomitant methotrexate at a stable dose (10-25 mg/week) until end of the study. The 24-week results are presented here. RESULTS: Equivalent efficacy between GP2015 and ETN was demonstrated if the 95% CI for the difference in disease activity score 28-joint count C reactive protein (DAS28-CRP) change from baseline to week 24 between treatment arms was contained within the prespecified equivalence margin range of -0.6 to 0.6. The least squares mean difference (GP2015-ETN) in change from baseline in DAS28-CRP up to week 24 was -0.07 (95% CI -0.26 to 0.12 [primary endpoint)]. The incidence of treatment-emergent adverse events was comparable between GP2015 (43.5%) and ETN (49.5%). None of the GP2015-treated patients developed neutralising anti-drug antibodies (NAbs) whereas 1.6% and 0.6% of patients in ETN group were NAb positive at weeks 4 and 12, respectively. CONCLUSION: In patients with RA who had an inadequate response to DMARDs, GP2015 demonstrated a similar efficacy and a comparable safety and immunogenicity profile with ETN. TRIAL REGISTRATION: NCT02638259.

Anthropology and psychiatry.

In this paper anthropology and psychiatry are defined as well as their scientific area, their methods and research objectives; the high level of their mutual thematic and methodological complementarity has been emphasized. The sociocultural factors which are inherent in the area of cultural anthropology can affect mental health in a number of ways: by forming a certain personality type that is predisposed for a certain type of disorder, by an education model which increases the frequency of some disorders, by criticism and sanctions of a certain behaviour that is actually desirable from the point of view of mental health preservation, by supporting and rewarding a behaviour model that is harmful for mental health; by its complexity and, in some of the segments, by mutual contradictions they can cause mental disorders; by forming symptoms of mental disorders i.e. by a pathoplastic action through which they become an area of scientific interest of cultural psychiatry. Anthropology directs psychiatry towards creating preventive and therapeutic programs that accept the mutual influence and interconnectedness of socio-cultural conditions and the mental health status.