Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS).

BACKGROUND: Classical Kaposi sarcoma (cKS) is a rare human herpesvirus 8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab in patients with previously treated progressive cKS. PATIENTS AND METHODS: cKS patients with progressive disease after one or more lines of systemic therapy and measurable disease by positron emission tomography/computed tomography and/or physical examination received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until progression or toxicity for a maximum of 24 months. The primary endpoint was overall response rate; secondary endpoints included 6-month progression-free survival (PFS) rate and safety. Immune correlates were explored using immunohistochemistry, DNA sequencing (596/648 genes) and RNA sequencing (whole transcriptome hybrid capture) of tumor specimens and matched blood. RESULTS: Eighteen male patients (median age 76.5 years) were enrolled between April 2018 and December 2020. At a median follow up of 24.4 months, overall response rate by RECIST v1.1 was 87%. Metabolic complete response as assessed by positron emission tomography/computed tomography was observed in 8 of 13 (62%) assessable patients. Some 6/13 achieved pathological complete response after treatment. In two patients, palliative limb amputation was prevented. Median PFS was not reached. The 6- month and 12-month PFS rate was 76.5% and 58.8%, respectively. Only four patients (22%) experienced grade 3-4 adverse events. The most frequent genomic alteration was biallelic copy number loss of the FOX1A gene. The majority of tumors carried a low tumor mutational burden, were microsatellite stable, mismatch repair proficient, did not express programmed death-ligand 1, and displayed only low lymphocytic infiltrates, rendering them immunologically 'cold'. CONCLUSIONS: This prospectively designed phase II study of nivolumab and ipilimumab demonstrates promising activity of this combination in progressive cKS representing a new treatment option in this population.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Objective measurement of oral function in adults with spinal muscular atrophy.

BACKGROUND: Impairment of bulbar function in adult individuals with spinal muscular atrophy (SMA) usually is not assessed by established motor scores. Measurements of oral function including quantitative muscle and endurance tests are able to detect subtle changes. The aim of this study was to systematically evaluate the measurement of maximum bite force and endurance, maximum tongue pressure and endurance, as well as maximum mouth opening in adult individuals with SMA types 2 and 3. METHODS: Data from oral function tests in 43 individuals were analyzed. Differences in oral function between individuals with different SMA types and numbers of SMN2 copies were tested. Spearman´s rho correlations among oral function measures themselves as well as with established clinical outcome scales were analyzed. RESULTS: The absolute maximum measures of oral function (maximum bite force, maximum tongue pressure, maximum mouth opening) were able to discriminate between individuals with different SMA types, individuals with a different number of SMN2 copies and with different walking abilities. The pairwise correlations of the absolute maximum measures of oral function were fair to moderate in size; the same was true for their correlations with the established motor scores. All correlations assessing endurance measures of oral function were weaker and statistically insignificant. CONCLUSIONS: Among the oral function tests maximum tongue pressure and maximum mouth opening are particulary promising as clinical and sensitive outcome measures for clinical trials. Oral function tests may supplement existing motor scores, in particular concerning specific questions about bulbar function or in severely affected non-ambulatory individuals where mild (treatment-related) changes would otherwise remain undetected. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/search/de/trial/DRKS00015842.

Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study.

BACKGROUND: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. METHODS: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. RESULTS: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. CONCLUSIONS: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

Geolocation with respect to personal privacy for the Allergy Diary app - a MASK study.

BACKGROUND: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data.To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. METHODS: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). RESULTS: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58.5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. DISCUSSION: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.

Elementary school students' attitudes toward science and their course of studies in high school.

This paper reports on a unique longitudinal study of adolescents which probes the relationship between the attitudes of grade 6 male and female students toward their school subjects as well as toward adult occupations and their actual course of study five years later. The findings indicate that there is almost no connection between these attitudes and their course of study in grade 11. However, a significant difference was found with regard to the importance grade six students assigned to the most scientific occupations and their future academic or nonacademic location in the course of study. The major finding is the importance of gender differences in their selection of courses of study based on the occupations they consider important. These gender differences are explained in light of general gender relations in society.

Possibilities and limitations of a gender stereotypes intervention program.

This study deals with an educational intervention program for elementary school teachers aimed at decreasing gender stereotypes. The limits of the educational program's effectiveness in relation to the theory of "relative autonomy of schools" is examined. The sample of sixth graders in this study was divided into two groups: the experiment group, whose teachers participated in the program's workshops, and the control group, whose teachers did not. It was hypothesized that (1) the experiment group would show greater preference for the more prestigious professions than would the control group. This hypothesis was supported in the main findings; (2) the experiment group would choose less gender-biased professions than would the control group. This hypothesis was only partially supported by the findings. Since school is only one of the many socializing factors in society, the effectiveness of this research was limited, as can be expected from the theory of the relative autonomy of schools.

Assimilation and ethnic boundaries: Israeli students' altitudes toward soviet immigrants.

The attitudes of Israeli students toward new immigrants from the former Soviet Union were examined against the theoretical framework of the sociology of ethnicity and sociology of education. The main research question explored was which ethnic relationship model (assimilation, pluralism, or separation) best described the attitudes and self-reported behavior of Israeli youth toward the new immigrants. Israeli students' changing attitudes toward their immigrant counterparts were also investigated, as well as actual Israeli educational practices (not only declared policies) regarding Soviet immigrants. The study was conducted in grades 4-11 at schools in northern Israel. The results indicated positive attitudes and openness of relations by the Israelis toward the new immigrant students in the first year following their immigration. However, the attitudes were less positive in the second year. Although the Israeli students manifested positive attitudes toward immigration and to the immigrants themselves, these views were largely assimilatory; Israeli cultural capital was obviously dominant, and it was expected to be accepted as such by the newcomers. The findings point to Israeli assimilatory educational practice; immigrants are expected to blend in, abandoning their past heritage and culture.

The relative autonomy of schools and educational interventions for substance abuse prevention, sex education, and gender stereotyping.

This paper evaluates intervention programs in schools using the theoretical framework of the critical sociology of education, and most specifically, the extent to which schools are autonomous from the larger society. Three different types of intervention programs are reviewed: drug abuse prevention, sex education, and programs to change gender stereotypes, all of which were found to have limited effectiveness. Schools appear unable to change behaviors which are prevalent in a culture because they themselves are strongly influenced by that culture, and because adolescents are influenced by forces outside school. To be effective, such interventions would seem to require governmental agencies, community groups, and the media to work with the schools in order to influence the culture and thus produce behavioral changes in individuals.

Teacher-student classroom interactions: the influence of gender, academic dominance, and teacher communication style.

Two Israeli grade 7 classes, with different teachers, were monitored and the lessons coded according to categories that were based on the conceptual framework of speech acts theory combined with role theory. The two classes differed in their academic composition: one class was dominated by females and the other was balanced by gender. Different classroom interactions were observed. The two teachers manifested different communication styles: one exercised more control, while the other was more influenced by the dominant students. The teachers did not have any bias against females; they were "gender blind." Thus, the findings indicated that gender, academic composition, and teacher communication style are important factors in teacher-student interactions.

The work productivity and activity impairment allergic specific (WPAI-AS) questionnaire using mobile technology: the MASK study

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Calcium carbimide in alcoholism treatment. Part 1: A placebo-controlled, double-blind clinical trial of short-term efficacy.

A randomized, double-blind, placebo-controlled single cross-over study of the alcohol sensitizing drug, calcium carbimide (CC), was conducted in 128 patients with alcohol dependence. Seventy-one (55%) completed the 4-month study. Patients reported drinking and pill-taking behaviour, and submitted urines (for analysis of alcohol and the tablet marker riboflavin) on 97%, and 91% of treatment days, respectively. All of the 69 analyzable completers were abstinent on at least 85% of days, and 58% (40) were alcohol-free during the study. Medications were taken on at least 85% of days. Symptoms and adverse clinical findings were not increased in frequency during CC, compared to placebo. Seventy-eight per cent of the patients believed they had received CC throughout the study, suggesting that CC exerts a strong psychological deterrent effect. Alcohol consumption was significantly reduced to the same extent with CC and placebo, compared to pre-treatment levels.