Baseline type 2 biomarker levels and response to tezepelumab in severe asthma.

BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER. METHODS: Adults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels. RESULTS: Positive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually. CONCLUSION: At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY.

BACKGROUND: Patients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo. OBJECTIVE: This analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY. METHODS: Adults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. PROs were assessed using the asthma control questionnaire-6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity. RESULTS: Overall, 550 patients were randomized. Up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity. CONCLUSION: Tezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.

Do Epidural Catheter Size and Flow Rate Affect Bolus Injection Pressure in Different Programmed Intermittent Epidural Bolus Regimens? An In Vitro Study.

BACKGROUND: The optimal programmed intermittent epidural bolus regimen for labor analgesia remains unknown. Some studies indicate that better drug spread in the epidural space results from greater injection pressure; however, there is a lack of data regarding the maximum pressure generated by epidural bolus injection using different catheters and flow rates. METHODS: We evaluated the flow and pressure characteristics of 11 commonly used epidural catheters combined with 3 different infusion pumps that deliver epidural infusions according to the programmed intermittent epidural bolus regimen. Pressure changes were measured over time at flow rates of 100, 250, and 400 mL·hour and with a bolus volume of 10 mL. To account for repeated measures, linear mixed models were used. Features were selected with a backward stepwise procedure continued until only statistically significant variables were left in the model. RESULTS: We performed 660 measurements. The mean maximal pressure generated during bolus injection ranged from 86 to 863 mm Hg for different flow rates and catheter designs. The interaction between flow rate and catheter gauge resulted in 1.31, 1.65, and 2.00 mm Hg of pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P< .001). Analyses including wire-reinforced catheters revealed a 1.16, 1.76, and 2.36 mm Hg pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P< .001). In some cases, it triggered the occlusion pump alarm. CONCLUSIONS: Significant differences were observed in the in vitro maximum pressure value among the various catheter and flow rate combinations with a higher pressure value for wire-reinforced catheters used in the study. The optimal flow rate and epidural catheter combination may allow for delivery of the bolus with high flow rate without triggering the occlusion alarm.

Abnormal lung ultrasound pattern during labor: A prospective cohort pilot study.

PURPOSE: Lung ultrasound (LUS) examination is used to evaluate patients with acute respiratory failure. The physiological LUS pattern during labor in healthy parturients has not been well described. The aim of this study was to evaluate the LUS pattern in a cohort of healthy women during uncomplicated labor. METHODS: We used the 8-point LUS assessment protocol and investigated lung sliding, A-lines, B-lines, interstitial syndrome, lung consolidation, and pleural effusion according to the International Consensus Document with two additional supradiaphragmatic projections. All patients were screened twice; once during the first stage of labor and again within 2 hours after delivery. RESULTS: We included 24 patients in this study from February 2014 to August 2015. A total of 480 LUS records were retained for further analysis. Overall, 16 of 24 patients (67%) had at least one positive region (three or more B-lines) during the peridelivery LUS evaluation. Interstitial syndrome was detected in five patients (21%). There were no differences in A-line (P = 0.38) or B-line (P = 0.68) prevalence between LUS examinations before and after delivery. CONCLUSIONS: Women in uncomplicated labor can present abnormal LUS findings, which may affect the interpretation of LUS results in patients with respiratory deterioration. Further studies should address this topic in larger cohort of patients.

Cardiovascular risk factors in patients with bicuspid aortic valve / Czynniki ryzyka chorób sercowo-naczyniowych u chorych z dwuplatkowa zastawka aorty

The bicuspid aortic valve (BAV) is a congenital heart disease. AIM: The aim of study was to evaluate the assessment of atherosclerosis risk factors in adult patients with bicuspid aortic valve compared against 30 healthy, age and sex matched volunteers. MATERIALS AND METHODS: Thirty patients (22 males, 8 females) at an average age of 27.00 ±10.6 years were compared against thirty healthy, age and sex matched volunteers. The arterial blood pressure, lipid profile, fasting glucose, inflammation markers and the lifestyle factors were analysed. RESULTS: Patients with bicuspid aortic valve have a higher level of glucose (4.95 vs 4.7 mmol / l, p = 0.026) and fibrinogen (2.25 vs. 1.98 g / l, p = 0.001) compared to the control group. In the group of patients with bicuspid aortic valve there was no hypertension, diabetes, tachycardia, stress exposure, alcohol abuse and a positive family history of cardiovascular diseases. CONCLUSIONS: The patients with bicuspid aortic valve have higher glucose and fibrinogen levels and they need systematic checking to reduce cardiovascular risk factors.

Is an emergency department a safer place for hypothermic victims than an ambulance? A comparison of the knowledge of medical personnel concerning hypothermia.

OBJECTIVE: Introduction: Improper initial management of a victim in severe hypothermia is associated with a risk of cardiac arrest. At the same time, an uncontrolled drop in core body temperature in trauma victims is an independent risk factor for mortality. Medical personnel require a thorough understanding of the pathophysiology and treatment of hypothermia. Gaps in this understanding can lead to serious complications for patients. The aim: To compare knowledge concerning hypothermia between medical personnel working in emergency departments (ED) and emergency medical services (EMS). PATIENTS AND METHODS: Materials and methods: A total of 5,362 participants were included in the study. In this study, EMS and ED personnel were encouraged to participate in an e-learning course on hypothermia. Subsequently, the scores of a pre-test, lesson tests and post-test completed by participants of this course were compared. RESULTS: Results: Pre-test scores were significantly higher among personnel working in EMS compared with those working in EDs. Nurses employed in EDs had significantly more failures in completing the course than EMS nurses. The most difficult topics for all practitioners were post-traumatic hypothermia and hypothermia-related clotting disorders. CONCLUSION: Conclusions: EMS personnel have a higher level of knowledge of hypothermia than ED personnel. Moreover, an e-learning course is an effective tool for improving medical personnel's knowledge of hypothermia.

[Cardiovascular risk factors in patients after coarctation of aorta repair]. / Czynniki ryzyka chorób sercowo-naczyniowych u chorych po leczeniu interwencyjnym koarktacji aorty.

The coarctation of the aorta (CoA) is a congenital condition of the thoracic aorta. AIM: The aim of the study was assessment of atherosclerosis risk factors in adult patients after surgical treatment of aortic coarctation. MATERIALS AND METHODS: 58 patients (36 male, 22 female) at median age of 27.46 ±10.57 were compared with 30 healthy, age and sex matched volunteers. The arterial blood pressure, lipid profile, fasting glucose, inflammation markers and the lifestyle factors were analyzed. RESULTS: CoA patients have higher systolic blood pressure 136.55±16.27 vs 123.47±10.34 mmHg, p<0.001, fasting glucose 4.95±0.5 vs 4.65±0.46 mmol/l p=0.002, hsCRP 1.03±0.12 vs 0.89±0.14 mg/l p=0.025 and fibrinogen 2.55±0.34 vs 1.98±0.28 g/l p<0.001. Hyperlipidemia is more common 44.8% vs 23.3% p=0.048, treated with statin. When comparing hypertensive patients (N=28) with normotensive ones (N=30), the patients with arterial hypertension are older 33.5±12.23 vs 25.73±7.12 p=0.004, have higher body weight 78.03±14.58 vs 68.7±14.29 p=0.017, in this group more common are: hypoplastic aortic arch 28.6% vs 6.7% p=0.027, recoarctation 39.3% vs 13.3% p=0.024, cardiovascular disease 14.3% vs 0% p=0.032 and family history 21.4% vs 3.3% p=0.034. CONCLUSIONS: The coarctation of aorta is related to higher cardiovascular risk due to arterial hypertension, hyperlipidemia, higher glucose and inflammation markers levels when comparing with healthy population.

Geometry of Koch's triangle.

AIMS: The first aim of this study was to determine the size of the Koch's triangle. The second one was to investigate relation between its dimensions and other individual-specific and heart-specific parameters as well as to create universal formula to estimate triangle dimensions based on these parameters. METHODS AND RESULTS: This study is a prospective one, presenting 120 randomly selected autopsied hearts dissected from adult humans (Caucasian) of both sexes (31.7% females), with mean age of 49.3 ± 17.4 years. The length of triangle sides and angles were measured and the triangle area was calculated as well. Sixteen additional heart parameters were measured in order to analyse potential relationship between the dimensions of Koch's triangle and other dimensions of the heart, using linear regression analysis. The mean (±SD) length of the anterior edge was approximated to 18.0 ± 3.8 mm, the posterior edge to 20.3 ± 4.3 mm, and the basal edge to 18.5 ± 4.0 mm. The average values of the apex angle, the Eustachian angle, and the septal leaflet angle were 58.0 ± 14.4°, 53.8 ± 10.6°, and 67.6 ± 14.4°, respectively. The mean value of the Koch's triangle area was 151.5 ± 55.8 mm2. The 95th percentile of triangle's height (the distance from the apex to the coronary sinus) was 21.8 mm. CONCLUSION: Mean values and proportions of triangle's sides and angles were presented. Koch's triangle showed considerable individual variations in size. The dimensions of the triangle were strongly independent from individual-specific and heart-specific morphometric parameters; however, the maximum triangle's height can be estimated as 22 mm.

Measuring core temperature using the proprietary application and thermo-smartphone adapter.

Fast and accurate measurement of core body temperature is crucial for accidental hypothermia treatment. We have developed a novel light and small adapter to the headset jack of a mobile phone based on Android. It has been applied to measure temperature and set up automatic notifications (e.g. Global Positioning System coordinates to emergency services dispatcher, ECMO coordinator). Its validity was confirmed in comparison with Vital Signs Monitor Spacelabs Healthcare Elance 93300 as a reference method, in a series of 260 measurements in the temperature range of 10-42 °C. Measurement repeatability was verified in a battery of 600 measurements (i.e. 100 readings at three points of 10, 25, 42 °C for both esophageal and tympanic catheters). Inter-method difference of ≤0.5 °C was found for 98.5% for esophageal catheter and 100% for tympanic catheter measurements, with concordance correlation coefficient of 0.99 for both. The readings were almost completely repeatable with water bath measurements (difference of ≤0.5 °C in 10 °C: 100% for both catheters; in 25 °C: 99% for esophageal catheter and 100% tympanic catheter; in 42 °C: 100% for both catheters). This lightweight adapter attached to smartphone and standard disposable probes is a promising tool to be applied on-site for temperature measurement in patients at risk of hypothermia.

[Assessment of knowledge about hypothermia among the medical personnel of polish medical air rescue].

Polish Medical Air Rescue is tasked to deal with the most serious incidents associated with life threatening situations, in multiple circumstances. As a consequence, medical personnel have to meet high standards of education and show a continuous theoretical and practical development of the skills which are necessary during medical treatment. Thanks to the introduction of ECMO treatment for accidental hypothermia patients, new clinical and operational possibilities have arisen, so more patients can be saved with a very good neurological outcome. AIM: To analyze the data on hypothermia collected by the personnel of Polish Medical Air Rescue and to assess the e-learning platform as an educational tool. MATERIALS AND METHODS: 123 persons were involved. The subject of analysis were the e-learning platform results of the Polish Medical Air Rescue medical personnel. The e-learning consisted of a pre-test, 8 lessons followed by MCQ's (multi choice questions) and a post-test. RESULTS AND CONCLUSIONS: We could not prove a statistically significant difference in the knowledge about hypothermia between doctors and other medical professionals. Post-traumatic hypothermia and associated coagulation disturbances are two important topics requiring particular focus during the design of further educational and training projects. As a consequence of the training, both groups significantly improved their knowledge: i.e. a statistically significant improvement of knowledge about hypothermia between pre-test and post-test results in both groups was shown. The hypothermia e-learning platform for medical personnel is an effective educational tool.

Impact of body weight on clinical symptoms and endoscopic changes in patients with gastroesophageal reflux disease.

Introduction: Gastroesophageal reflux disease (GERD) is connected with body mass index (BMI) according to some recent studies. However, the link between overweight and severity of GERD symptoms is still unclear. Objectives: The aim of our study is to assess the influence of BMI on clinical presentation and occurrence of inflammatory changes in the esophagus in patients with GERD. Material and Methods: 121 clinically diagnosed GERD patients: 66 males (54.5%) and 55 females (45.5%), aged 19 ­ 89 years were involved in the study. After the detailed anamnesis BMI was counted and gastroscopy was performed. All individuals who agreed for upper endoscopy were divided into three groups. 42 patients (34.7%) were classified as Non-Erosive Reflux Disease (NERD), 53 patients (43.8%) were diagnosed with Erosive Esophagitis (EE), 11 patients (9.1%) with Barrett's esophagus (BE). Among EE group 34 patients were diagnosed with grade A of esophagitis according to Los Angeles scale, 17 with grade B, 2 with grade C and none with grade D. The differences between groups were assessed using statistical analysis. Results: The mean age of patients was 50.2±12.9 years and the mean BMI was 25.5±4.2 kg/m2. Patients with BE were older (61.2±12.0 years) than NERD (48.5±13.6 years); (p=0.028) and EE (50.4±11.4 years); (p=0.008). BE had higher BMI (27.0±4.4 kg/m2) as compared to NERD (24.0±3.3 kg/m2); (p=0.022) and EE (24.4±3.1 kg/m2); (p=0.048). Hiatal hernia was more frequent in EE and BE (79.2% and 90.9%, respectively) as compared to NERD (45.2%); (p<0.001). Patients EE and BE more frequently complained to heartburn (84.9% and 72.7%, respectively) than patients with no mucosal injury (42.9%); (p<0.001). Sleeping problems were encountered by patients with higher levels of BMI. Conclusion: This study demonstrates that overweight predispose to esophageal inflammation and increase the frequency of heartburn and sleep problems in GERD patients.

[Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study]. / Wplyw dawki prowokacyjnej aspiryny na poziom prostaglandyny E2 w plwocinie indukowanej u chorych na astme z i bez nadwrazliwosci na aspiryne oraz u osób zdrowych--badanie pilotazowe.

The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

[Correlations between the perception of family functioning by patients with eating disorders and their parents and the perception of relations in the parents' families of origin]. / Powiazania pomiedzy spostrzeganiem funkcjonowania rodziny przez pacjentki z zaburzeniami od4ywiania sie i ich rodziców a percepcja relacji w rodzinach pochodzenia rodziców.

AIM OF THE STUDY: To assess the correlations between the perception of relations in parents' families of origin and the assessment of the current family by the parents and their daughters suffering from eating disorders. STUDIED GROUP: Statistical analyses were applied to the results obtained from 54 patients diagnosed with restrictive anorexia nervosa, from 22 with binge-purge anorexia, from 36 with bulimia and from two control groups: 36 patients diagnosed with depressive disorders and 85 Krakow schoolgirls. The study also covered the parents of the investigated girls. METHOD: Family of Origin Scale and Family Assessment Questionnaire (FAM Polish version) were used in the study. RESULTS: The procreative family assessment made by the mothers was correlated with the assessment of their own generational family and the assessment of own generational family made by their husbands. Procreative family assessment made by the fathers was correlated only with their assessment of their family of origin. Family of origin assessment made by patients with diagnosed eating disorders, particularly bulimia, was correlated only with the family of origin assessment made by their fathers. The last correlation did not occur in the control groups. CONCLUSIONS: The research shows a correlation between the experience of the families of origin and the current functioning of the family. They show the impact of the fathers' trangenerational experience on the perception of family relations of daughters with diagnosed anorexia and bulimia nervosa.

Homocysteine in patients with inflammatory bowel diseases.

BACKGROUND: Hyperhomocysteinemia seems to be a common phenomenon in both patients with ulcerative colitis and Crohn's disease. Many factors including deficiencies of cobalamin, folate and pyridoxine, smoking habits, alcohol and coffee intake, some medications and age may predispose subjects to hyperhomocysteinemia. The study aimed to evaluate homocysteine levels in an inflammatory bowel disease cohort as dependent of life style and disease activity. METHODS: 85 consecutive patients with inflammatory bowel disease (38 with Crohn's disease and 47 with ulcerative colitis) and 65 control subjects were included in the prospective study. The following parameters were analyzed: disease activity, duration of the disease, location of pathological changes, presence of complications, current medications, past surgical procedures, smoking history, concomitant diseases, biochemical parameters and plasma homocysteine levels. RESULTS: Mild hyperhomocysteinemia was found in 16 patients with Crohn's disease (42%), 19 patients with ulcerative colitis (40%) and 19 patients in the control group (29%) (p = 0.59). There was not any significant correlation between homocysteine level and disease activity. Only folic acid supplementation and gender affected homocysteine level. Folic acid intake led to reduction of homocysteine levels in all groups of patients (11.8 micromol/l vs. 8.33 miccromol/l, p = 0.0065 in Crohn's disease patients and 10.94 micromol/l vs. 7.78 micromol/l, p = 0.0069 in ulcerative colitis patients). CONCLUSION: Homocysteine level in patients with inflammatory bowel disease is mostly normal or slightly elevated. Disease activity does not have an impact on homocysteine level. Folic acid is the most important factor having an influence on homocysteine level in patients with inflammatory bowel disease.

[The relationship between assessment of family relationships and depression in girls with various types of eating disorders]. / Zwiazek oceny relacji rodzinnych z depresja u dziewczat z róznymi typami zaburzen odzywiania sie.

AIM: The aim of the study was to assess the relationship between depressive symptoms and girls' assessment of their family relations in a group of (female) patients with a diagnosis of various subtypes of eating disorders in comparison with (female) patients with a diagnosis of depressive disorders (episode of major depression, dysthymia, adjustment reaction with depressive mood) and female students in Krakow, Poland schools. METHOD: Data from 54 (female) patients with a diagnosis of restrictive anorexia (ANR), 22 with a diagnosis of binge-purge anorexia (ANB), 36 with a diagnosis of bulimia (BUL), 36 with a diagnosis of depressive disorders (DEP) and a 85 (female) Krakow school students (CON) were used in the statistical analyses. There were no significant differences between age of the girls in studied groups. In analyses, results of the Polish version of the Beck Depression Inventory (BDI) and also the Family Assessment Questionnaire (KOR) were used. RESULTS: In the CON group, correlations attesting to a link between depressiveness and a negative assessment of the family were observed on all scales of the questionnaire with the exception of the Values and Norms scale. In the DEP group, such a dependence was ascertained on scales: Completing Tasks, Communication, Emotionality, Control, Defence, Positive Statements. In the case of the ANR group, no statistically significant relationship between results of the questionnaires was noted. In group ANB, correlations attesting to a link between depressiveness and a negative picture of the family were ascertained on scales: Communication and Defence. The same dependence was ascertained in the BUL group on scales: Completing Tasks, Emotionality, Emotional involvement, Control, General result, Negative Statements. CONCLUSIONS: An increase in depressiveness is linked in a significant way with a worsening assessment of the family relations amongst girls with a diagnosis of bulimia, depressive disorders and students.

Disordered eating among mothers of Polish patients with eating disorders.

BACKGROUND: The aim of this study was to assess attitudes towards eating as measured by the Eating Attitude Test (EAT26) among mothers of girls diagnosed with various types of eating disorders, in comparison with mothers of depressive girls and their relationship with daughters' results 14 years after the beginning of the Polish political and cultural transformation of 1989. MATERIAL/METHODS: The data of 68 mothers and their daughters were used in statistical analysis (anorexia nervosa restrictive type: 18, anorexia nervosa binge/purge type: 12, bulimia: 14, depression: 24). The mean age in the group of mothers was 43.5 (SD 5.3), daughters: 16.7 (SD 1.4). RESULTS: In the group of mothers, the results of EAT26 test were lower than results of the general population of Polish females or patients' mothers obtained in a different cultural context. Results from girls with an eating disorder diagnosis considerably exceed the mean result of Polish population studies of teenagers. There were no statistically significant differences between the EAT26 results of mothers of girls with various types of eating disorders and mothers of depressive girls. Sociocultural variables such as education and place of residence of mothers also did not differentiate the studied groups and did not have a significant influence on attitudes towards weight and body shape presented by the studied mothers. CONCLUSIONS: The obtained results may suggest that in the studied population, the social background of mothers and disturbances of their own mothers' attitudes towards weight and body shape were not an important and specific risk factor in the development of their daughters' eating disorders.

[The cultural context of eating disorders--own research]. / Kontekst kulturowy zaburzen odzywiania sie--badania wlasne.

AIM: To assess cultural attitudes and beliefs among (female) patients being treated for various kinds of eating disorders in comparison with (female) patients diagnosed with depression and healthy girls. METHOD: Version II of the Cultural Questionnaire by M. Pilecki and B. Józefik referring to issues linked with those aspects of dulture whose importance is described as significant in the development of eating disorders. MATERIAL: Data from patients with the following diagnoses were used in the statistical analyses: 54 (female) patients with a diagnosis of restrictive anorexia (ANR), 22 with a diagnosis of binge-purge anorexia (ANB), 36 with a diagnosis ofbulimia (BUL) and 40 with a diagnosis of depressive disorders (DEP) and also 74 female pupils from Kraków schools (KON). RESULTS: Groups ANB and BUL obtained high scores, indicating the greater significance of 'ideals of thinness' in their lives than in groups KON, DEP and ANR. The BUL group was characterised by a sense of yielding to fashion pressure and also by a sense of the environmental and generational significance of the disorders in relation to groups KON and DEP. The females in group KON assessed that their parents attached greater importance to appearance than did (female) patients in group ANB. A negative evaluation of the position of women in the family was given by all the studied (female) patients in comparison with group KON. CONCLUSIONS: The obtained results may indicate the greater significance of cultural mechanisms in bulimia than anorexia nervosa. They may also be an expression of the limited possibility of introspection of girls with a diagnosis of restrictive anorexia. A negative perception of femininity in the family and culture accompanies not only eating disorders, but also depressive disorders.

Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study.

BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma. METHODS: We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078. FINDINGS: Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per µL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per µL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group. INTERPRETATION: We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per µL. FUNDING: AstraZeneca and Amgen.

Tezepelumab Pharmacokinetics, Safety, and Tolerability After Administration via Vial-and-syringe, Accessorized Prefilled Syringe, or Autoinjector: A Randomized Trial in Healthy Volunteers.

PURPOSE: Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V-S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V-S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI). METHODS: This single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18-65 years. Participants, stratified according to weight (50 to <70 kg, 70 to <80 kg, or 80-90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V-S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of Cmax and AUC0-∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed. FINDINGS: A total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of Cmax, AUC0-∞, and AUC0-last were close to 1, with 90% CIs all within the range of 0.8-1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V-S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V-S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V-S, APFS, and AI groups. Median visual analog scale pain score (0-100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups. IMPLICATIONS: Tezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V-S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V-S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.

Perceptions of Fear, Likelihood of Victimization, and Confidence About Dangerous Situations Among University Women in Poland.

Polish women have not been studied in regard to fear, likelihood, or confidence about dangerous situations, nor has there been an instrument to measure those perceptions. The purpose of the study was fourfold: first, to present the Polish translation and validation of the Perception of Dangerous Situations Scale (PDSS-P) and second, to assess Polish women's perceived fear, likelihood, and confidence about dangerous situations using the PDSS-P (41 items). The third purpose was to determine to what degree the General Self-Efficacy Scale (GSES) and/or the Hope for Success Scale (KNS) correlated with any of the three subscales of the PDSS-P. The fourth purpose was to determine the congruence of the PDSS-P to the original PDSS. Two other tools (GSES and KNS) were administered to determine concurrent validity with the PDSS. A sample of 208 women aged 19 to 27 years (M = 21.04, SD = 1.88) participated in the study. Five factors were determined for each subscale, similar to the original version of the PDSS. Women reported they were more afraid of being raped by a stranger than being murdered. Their estimation of the likelihood of some serious events occurring was not congruent with statistical realities. The women thought the least likely events to happen to them in the next year would be being raped or beaten by someone they know, or being held prisoner by someone who wanted to murder them. Confidence to manage dangerous situations was low in cases of being raped by strangers or known people, being kidnapped, or being attacked. The GSES and KNS provided useful information, in that they did not measure the same constructs as the PDSS-P.