Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

ABSTRACT: Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a gluten-free diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with C

175 years of bilirubin testing : ready for point-of-care?

Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point-of-care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated

Humor in radiological breast cancer screening: a way of improving patient service?

BACKGROUND Breast cancer screening is essential in detecting breast tumors, however, the examination is stressful. In this study we analyzed whether humor enhances patient satisfaction. METHODS In this prospective randomized study 226 patients undergoing routine breast cancer screening at a single center during October 2020 to July 2021 were included. One hundred thirty-two were eligible for the study. Group 1 (66 patients) received an examination with humorous intervention, group 2 (66 patients) had a standard breast examination. In the humor group, the regular business card was replaced by a self-painted, humorous business card, which was handed to the patient at the beginning of the examination. Afterwards, patients were interviewed with a standardized questionnaire. Scores between the two study groups were compared with the Mann-Whitney U test or Fisher's exact test. P-values were adjusted with the Holm's method. Two-sided p-values < 0.05 were considered significant. RESULTS One hundred thirty-two patients, 131 female and 1 male, (mean age 59 ± 10.6 years) remained in the final study cohort. Patients in the humor group remembered the radiologist's name better (85%/30%, P < .001), appreciated the final discussion with the radiologist more (4.67 ± 0.73-5;[5, 5] vs. 4.24 ± 1.1-5;[4, 5], P = .017), felt the radiologist was more empathetic (4.94 ± 0.24-5;[5, 5] vs.4.59 ± 0.64-5;[4, 5], P < .001), and rated him as a humorous doctor (4.91 ± 0.29-5;[5, 5] vs. 2.26 ± 1.43-1;[1, 4], P < .001). Additionally, patients in the humor group tended to experience less anxiety (p = 0.166) and felt the doctor was more competent (p = 0.094). CONCLUSION Humor during routine breast examinations may improve patient-radiologist relationship because the radiologist is considered more empathetic and competent, patients recall the radiologist's name more easily, and value the final discussion more. TRIAL REGISTRATION We have a general approval from our ethics committee because it is a retrospective survey, the patient lists for the doctors were anonymized and it is a qualitative study, since the clinical processes are part of the daily routine examinations and are used independently of the study. The patients have given their consent to this study and survey

Smoking trends and health equity in Switzerland between 1992 and 2017: dependence of smoking prevalence on educational level and social determinants

BackgroundSwitzerland ranks among the top three healthcare systems in the world with regards to healthcare access, suggesting a high degree of health equity. However, Switzerland has few preventive strategies against smoking abuse. The aim of this study is to clarify whether educational level and citizenship status have an influence on the prevalence of smoking in Switzerland and whether there is health inequity related to a lack of preventive strategies.MethodsWe based our analysis on publicly available health data published in the Swiss government's Swiss health survey (1992–2017). We compared the prevalence of smoking across the years and correlated these data with levels of educational attainment, citizenship status and age.ResultsA continuous significant decline in smokers is observed in the highest education group (TERT). Over time, prevalence was reduced from 29% in 1992 to 23% in 2017 (p &lt; 0.001). The intermediate-level educational group (SEK 2) showed smaller but also significant decline on a 0.05 sigificance level over the same period, from 31% to 29% (p = 0.003). The lowest educational group showed a nonsignificant decline from 28% to 27% (p = 0.6). The population who holds Swiss citizenship showed a decrease in smoking from 28% to 26% within the time frame (p &lt; 0.001). People without Swiss citizenship had a much higher prevalence of smokers, at 38% in 1992 and declining to 32% in 2017 (p &lt; 0.001). All cohorts from age 15 to age 64 have a far higher prevalence of smokers than cohorts at an older age, with the highest prevalence in the 25–34 age group.ConclusionIn Switzerland, individuals with lower levels of education and non-Swiss populations are more susceptible to health risk of smoking. This is despite the existence of a high-quality healthcare system that has nevertheless failed to negated health inequities

Twenty-five years of polymersomes: lost in translation?

Soon after the discovery of polymeric vesicles (polymersomes), reports of their high membrane stability raised hopes for the development of next generation vesicles for drug delivery and diagnostic applications. Twenty-five years later, however, liposomes remain the only clinically tested colloidal vesicular formulations. To highlight the translational challenges faced by polymersomes, we critically reviewed a selection of polymersome formulations with a focus on their pharmacokinetic and pharmacodynamic aspects.ISSN:2051-6347ISSN:2051-635

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

ISSN:0724-8741ISSN:1573-904

Drug delivery breakthrough technologies – A perspective on clinical and societal impact

The way a drug molecule is administered has always had a profound impact on people requiring medical interventions - from vaccine development to cancer therapeutics. In the Controlled Release Society Fall Symposium 2022, a trans-institutional group of scientists from industry, academia, and non-governmental or�ganizations discussed what a breakthrough in the field of drug delivery constitutes. On the basis of these discussions, we classified drug delivery breakthrough technologies into three categories. In category 1, drug delivery systems enable treatment for new molecular entities per se, for instance by overcoming biological barriers. In category 2, drug delivery systems optimize efficacy and/or safety of an existing drug, for instance by directing distribution to their target tissue, by replacing toxic excipients, or by changing the dosing reqimen. In category 3, drug delivery systems improve global access by fostering use in low-resource settings, for instance by facilitating drug administration outside of a controlled health care institutional setting. We recognize that certain breakthroughs can be classified in more than one category. It was concluded that in order to create a true breakthrough technology, multidisciplinary collaboration is mandated to move from pure technical inventions to true innovations addressing key current and emerging unmet health care needs

An MRI-guided HIFU-triggered wax-coated capsule for supertargeted drug release: a proof-of-concept study

Background Externally controlling and monitoring drug release at a desired time and location is currently lacking in the gastrointestinal tract. The aim of the study was to develop a thermoresponsive wax-coated capsule and to trigger its release upon applying a magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (HIFU) pulse. Methods Capsules containing a lyophilised gadolinium-based contrast agent (GBCA) were coated with a 1:1 (mass/mass) mixture of lanolin and cetyl alcohol (melting point ≈43 °C) and exposed to simulated gastric and intestinal fluids (United States Pharmacopoeia) at 37 °C for 2 and 24 h, respectively. In a HIFU gel phantom, wax-coated capsules (n = 3) were tracked based on their T1- and T2-hypointensity by 1.5-T T1- and T2-weighted MRI pre- and post-exposure to an MRI-guided HIFU pulse. Results Lanolin/cetyl alcohol-coated capsules showed high resistance to simulated gastrointestinal fluids. In a gel phantom, an MRI-guided HIFU pulse punctured the wax coating, resulting in the hydration and release of the encapsulated lyophilised GBCA and yielding a T1-hyperintense signal close to the wax-coated capsule. Conclusion We provide the proof-of-concept of applying a non-invasive MRI-guided HIFU pulse to actively induce the disintegration of the wax-coated capsule, and a method to monitor the release of the cargo via T1-weighted MRI based on the hydration of an encapsulated lyophilised GBCA. The wax-coated capsule platform enables temporally and spatially supertargeted drug release via the oral route and promises to address a currently unmet clinical need for personalised local therapy in gastrointestinal diseases such as inflammatory bowel diseases and cancer.ISSN:2509-928

Incidence of transient interruption of contrast (TIC) – A retrospective single-centre analysis in CT pulmonary angiography exams acquired during inspiratory breath-hold with the breathing command: “Please inspire gently!”

Objectives To assess the occurrence of transient interruption of contrast (TIC) phenomenon in pulmonary computed tomography angiography (CTPA) exams performed in inspiratory breath-hold after patients were told to inspire gently. Methods In this retrospective single-centre study, CTPA exams of 225 consecutive patients scanned on a 16-slice CT scanner system were analysed. A-priori to measurements, exams were screened for inadequate pulmonary artery contrast due to incorrect bolus tracking or failure of i.v. contrast administration. Those exams were excluded. Attenuation values in the thoracic aorta and in the pulmonary trunk were assessed in duplicate measurements (M1 and M2) and the aorto-pulmonary density ratio was calculated. An aorto-pulmonary ratio > 1 with still contrast inflow being visible within the superior vena cava was defined as TIC. Results 3 patients were excluded due to incorrect bolus tracking. Final analysis was performed in 222 patients (mean age 65 ± 19 years, range 18 to 99 years). Mean density in the pulmonary trunk was 275±17 HU, in the aorta 208 ± 15 HU. Mean aorto-pulmonary ratio was 0.81± 0.29. 48 patients (21.6%) had an aorto-pulmonary ratio >1. Correlation of mean aorto-pulmonary ratio and age was: -0.213 (p = 0.001). Age was not significantly different for an aorto-pulmonary ratio >1 vs. ≤1 (p = 0.122). Both in M1 and M2, 33/222 patients presented with absolute HU values of < 200 HU within the pulmonary artery. In M1 measurements, 24 of these 33 patients (72%) fulfilled TIC criteria (M2: 25/33 patients (75%)). Conclusions TIC is a common phenomenon in CTPA studies with inspiratory breath-hold commands after patients were told to inspire gently with an incidence of 22% in our retrospective cohort. Occurrence of TIC shows a significant negative correlation with increasing age and disproportionately often occurs in patients with lower absolute contrast density values within their pulmonary arteries.ISSN:1932-620