PURPOSE Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, ...placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio HR, 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
We report on an experimental study that explores cross-cultural differences in perception of trustworthiness based on facial traits. In the first part of the experiment, individual male and female ...neutral photographs of Buryats (Mongolian people of Eastern Siberia) were rated on trustworthiness by men and women from the same population. The trustworthy-looking facial traits were investigated by means of geometric morphometrics, and analysis of the facial action units using artificial neural network (FaceReader). Significant associations between facial traits and perceived trustworthiness were revealed only for male photographs rated by men. Facial shape pattern along trustworthy–untrustworthy vector corresponded to the facial femininity-masculinity vector for Buryats, as well as to the positive-negative vector of the emotional connotation of the neutral facial shape. “Untrustworthy” facial shape was characterized by relatively narrower lower jaw, lower set eyebrows, as well as a lower position of the “Brow Lowerer” facial action unit—a frown. In the second part of the experiment, two geometric morphometric morphs, representing “trustworthy” and “untrustworthy” Buryat male facial shapes, were judged on trustworthiness by male representatives of Buryat, Tuvan (Mongolian people of Southern Siberia), Russian, Indian, and East African (Tanzanians) cultures. The results revealed that in all studied samples the “trustworthy” male portrait was rated significantly higher on trustworthiness than “untrustworthy” one. However, perceived trustworthiness, and agreement of portrait judgments with those of Buryats significantly declined with geographic and genetic distance between populations.
Background Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. Objective To evaluate the effectiveness of a new recombinant ...birch pollen allergen vaccine in patients with birch pollen allergy. Methods A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 μg Bet v 1 for 2 years. Results Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities ( P < .0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1–specific IgG levels, which were higher in the rBet v 1–treated group than in the birch and nBet v 1–treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1–treated or 29 nBet v 1–treated patients. No severe systemic adverse events were observed in the rBet v 1–treated group. Conclusion The rBet v 1–based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.
Previous research has demonstrated that Maasai and Europeans tend to align in their ratings of the physical strength and aggressiveness of Maasai male faces, calibrated to hand grip strength (HGS). ...However, perceptions of attractiveness of these faces differed among populations. In this study, three morphs of young Maasai men created by means of geometric morphometrics, and depicting the average sample and two extrema (± 4 SD of HGS), were assessed by men and women from Tanzania, Czech Republic, Russia, Pakistan, China, and Mexico (total sample = 1540). The aim of this study was to test cross-cultural differences in the perception of young Maasai men's composites calibrated to HGS, focusing on four traits: physical strength, attractiveness, aggressiveness, and helpfulness. Individuals from all six cultures were able to distinguish between low, medium, and high HGS portraits. Across all study populations, portrait of Maasai men with lower HGS was perceived as less attractive, more aggressive, and less helpful. This suggests that people from diverse populations share similar perceptions of physical strength based on facial shape, as well as attribute similar social qualities like aggressiveness and helpfulness to these facial images. Participants from all samples rated the composite image of weak Maasai men as the least attractive.
The COVID-19 restrictions have impacted people's lifestyles in all spheres (social, psychological, political, economic, and others). This study explored which factors affected the level of anxiety ...during the time of the first wave of COVID-19 and subsequent quarantine in a substantial proportion of 23 countries, included in this study. The data was collected from May to August 2020 (5 June 2020). The sample included 15,375 participants from 23 countries: (seven from Europe: Belarus, Bulgaria, Croatia, Hungary, Italy, Romania, Russia; 11 from West, South and Southeast Asia: Armenia, India, Indonesia, Iran, Iraq, Jordan, Malaysia, Pakistan, Saudi Arabia, Thailand, Turkey; two African: Nigeria and Tanzania; and three from North, South, and Central America: Brazil, Canada, United States). Level of anxiety was measured by means of the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 20-item first part of The State-Trait Anxiety Inventory (STAI)-State Anxiety Inventory (SAI). Respondents were also asked about their personal experiences with COVID-19, attitudes toward measures introduced by governments, changes in attitudes toward migrants during a pandemic, family income, isolation conditions, etc. The factor analysis revealed that four factors explained 45.08% of variance in increase of anxiety, and these components were interpreted as follows: (1) personal awareness of the threat of COVID-19, (2) personal reaction toward officially undertaken measures and attitudes to foreigners, (3) personal trust in official sources, (4) personal experience with COVID-19. Three out of four factors demonstrated strong associations with both scales of anxiety: high level of anxiety was significantly correlated with high level of personal awareness of the threat of COVID-19, low level of personal reaction toward officially undertaken measures and attitudes to foreigners, and high level of presence of personal experience with COVID-19. Our study revealed significant main effects of sex, country, and all four factors on the level of anxiety. It was demonstrated that countries with higher levels of anxiety assessed the real danger of a pandemic as higher, and had more personal experience with COVID-19. Respondents who trusted the government demonstrated lower levels of anxiety. Finally, foreigners were perceived as the cause of epidemic spread.
ABSTRACT
Objective: To assess the efficacy and onset of action of azelastine nasal spray and desloratadine tablets in patients with allergen-induced seasonal allergic rhinitis (SAR).
Research design ...and methods: 46 adult patients with a history of SAR were exposed to a controlled grass pollen concentration for 6 h in the Vienna Challenge Chamber (VCC) in each treatment period according to a randomised, double-blind (double-dummy), three-period, three-sequence crossover design (wash-out period of 12 days). Single doses of study medication (one puff nasal spray into each nostril of azelastine, 0.28 mg, or placebo before swallowing one encapsulated tablet of desloratadine, 5 mg) were administered 2 h after the start of the allergen challenge. Results of subjective and objective assessments were recorded throughout the challenge.
Results: Efficacy of azelastine nasal spray was significantly superior compared to desloratadine tablets ( p = 0.005) and placebo ( p < 0.001). Desloratadine was significantly better than placebo ( p < 0.001). Decrease both in Major Nasal Symptom Score (MNSS) and in Total Nasal Symptom Score (TNSS) was fastest after azelastine treatment. Improvement of nasal symptom severity was most pronounced after azelastine treatment for all nasal symptoms including nasal congestion. Onset of action was 15 min for azelastine compared to 150 min for desloratadine. Both active preparations were safe and well tolerated.
Conclusions: This study confirms the usefulness of azelastine nasal spray for the symptomatic treatment of seasonal allergic rhinitis. Concerning onset of action in particular, the results favour the topical treatment over systemic therapy.
The therapeutic efficacy and tolerability of emedastine difumarate (CAS 87233-62-3) in male and female Caucasian patients with seasonal allergic rhinitis as compared to cetirizine (CAS 83881-51-0) ...was evaluated.
The study was designed as a double-blind, randomised, parallel groups comparison of two antihistamines administered by oral route (emedastine 4 mg o.d. versus cetirizine 10 mg o.d.) in a population of 120 patients suffering from grass pollen allergic rhinitis. The duration of the treatment period was 14 days. Primary efficacy variable was a total symptoms score (including among symptoms nasal congestion, sneezing, rhinorrhea, nasal/throat/palate itching, eye itching and lacrimation) evaluated after 14 days of treatment vs. baseline value. Safety was assessed on routine laboratory assays and recording vital signs and adverse events (AEs).
The between-group difference in primary efficacy variable averaged over the 2-week treatment period was not statistically significant. Results clearly showed that no significant difference exists between the two treatments as far as total symptoms score evaluated after 14 days of treatment vs. baseline values are concerned. Therefore, the efficacy profiles of the study medications are overlapping. The pattern and incidence of AEs was similar in both treatment groups. The most frequent AEs with both compounds were related to the CNS, headache being the most reported one. In particular, this study seems to disclose a slighter tendency to drowsiness with emedastine than with cetirizine.
Both drugs under investigation in this trial appear to be effective for relieving the symptoms of seasonal allergic rhinitis in Caucasian adult patients. The results demonstrate that emedastine 4 mg o.d. is comparable in efficacy to cetirizine 10 mg once daily in the symptomatic management of seasonal allergic rhinitis. Moreover, based on the results of this study, emedastine can be considered a safe and well-tolerated drug and its safety profile seems to resemble that of cetirizine.
BackgroundThe symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described.MethodsRetrospective analysis of ...401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness.Results75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge.ConclusionsPatients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.
PDF
