METHODS: Between 2017-2018, a cross-sectional European Tinnitus Survey (ETS) was conducted in 12 European Union nations (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain), using a standardised set of tinnitus-related questions and response options in country-specific languages. We recruited 11,427 adults aged ≥18 years.
FINDINGS: Prevalence of any tinnitus was 14·7% (14·0% in men and 15·2% in women), ranging from 8·7% in Ireland to 28·3% in Bulgaria. Severe tinnitus was found in 1·2% participants (1·0% in men and 1·4% in women), ranging from 0·6% in Ireland to 4·2% in Romania. Tinnitus prevalence significantly increased with increasing age and worsening of hearing status. Healthcare resource use for tinnitus increased with increasing tinnitus symptom severity.
INTERPRETATION: This is the first multinational report of Pan-European tinnitus prevalence using standardised questions. The overall prevalence estimates refine previous findings, although widespread inter-country heterogeneity was noted. The results indicate that more than 1 in 7 adults in the EU have tinnitus. Extrapolating to the overall population, approximately 65 million adults in EU28 have tinnitus, 26 million have bothersome tinnitus and 4 million have severe tinnitus.
FUNDING: National Institute for Health Research, European Union's Horizon 2020, Medical Research Council, and GENDER-Net Co-Plus Fund.
METHODS: This was a cross-sectional study conducted between 12 June 2020 to 26 July 2021. An online survey was administered via email and social media to Malaysians in the Selangor and Kuala Lumpur communities. Respondents were over 18 years old, without a formal diagnosis of hypertension. The survey evaluated hypertension knowledge, Health Belief Model constructs, self-care behaviour frequency, and motivators and barriers to self-care behaviour. Multiple linear regression was performed to determine the main predictors of self-care behaviour, and descriptive statistics were used to characterise motivators and barriers of each self-care behaviour.
RESULTS: Only health motivations (β = 0.217, p < 0.001) and perceived barriers (β = 0.571, p < 0.001) significantly influenced self-care behaviour. Maintaining a healthy diet, regular physical activity and blood pressure checks need to be improved in the community, particularly in reducing salt and calorie intake. Lack of time, limited choices and laziness are the biggest challenges that need to be tackled in adopting a healthy diet and an active lifestyle in the community. Many are ignorant towards their health status, therefore, do not prioritize blood pressure screenings, suggesting a need to enhance community blood pressure checks for early diagnosis of hypertension.
CONCLUSION AND IMPLICATIONS: Motivations and barriers were the main determinants of self-care behaviour in the Selangor and Kuala Lumpur community. Targeting these aspects of self-care behaviour should be considered when developing interventions and education programmes tailored to local cultural, environmental and personal factors, to more effectively reduce the hypertension prevalence and burden.
METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity.
RESULTS: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab.
CONCLUSIONS: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.).
EXPERIMENTAL APPROACH: We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca(2) (+) sparks in intact adult rat cardiac myocytes.
KEY RESULTS: Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca(2) (+) spark frequency.
CONCLUSIONS AND IMPLICATIONS: Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca(2) (+) sparks is likely, by analogy with flecainide, to result from Na(+) channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na(+) and RyR2 channels.