Heart rate variability during a cognitive reappraisal task in female patients with borderline personality disorder: the role of comorbid posttraumatic stress disorder and dissociation.

BACKGROUND: Emotion dysregulation is a core feature of borderline personality disorder (BPD), which often co-occurs with posttraumatic stress disorder (PTSD). Difficulties in emotion regulation (ER) have been linked to lower high-frequency heart rate variability (HF-HRV), a measure of autonomous nervous system functioning. However, previous research on vagally-mediated heart rate in BPD revealed heterogeneous findings and the effects of comorbid PTSD and dissociation on HF-HRV are not yet completely understood. This study aim to investigate HF-HRV during resting-state and an ER task in female BPD patients with comorbid PTSD (BPD + PTSD), patients without this comorbidity (BPD), and healthy controls (HC). METHODS: 57 BPD patients (BPD: n = 37, BPD + PTSD: n = 20) and 27 HC performed an ER task with neutral, positive, and negative images. Participants were instructed to either attend these pictures or to down-regulate their upcoming emotions using cognitive reappraisal. Subjective arousal and wellbeing, self-reported dissociation, and electrocardiogram data were assessed. RESULTS: Independent of ER instruction and picture valence, both patient groups (BPD and BPD + PTSD) reported higher subjective arousal and lower wellbeing; patients with BPD + PTSD further exhibited significantly lower HF-HRV compared with the other groups. Higher self-reported state dissociation predicted higher HF-HRV during down-regulating v. attending negative pictures in BPD + PTSD. CONCLUSIONS: Findings suggest increased emotional reactivity to negative, positive, and neutral pictures, but do not provide evidence for deficits in instructed ER in BPD. Reduced HF-HRV appears to be particularly linked to comorbid PTSD, while dissociation may underlie attempts to increase ER and HF-HRV in BPD patients with this comorbidity.

Inhibition of the PI3K but not the MEK/ERK pathway sensitizes human glioma cells to alkylating drugs.

BACKGROUND: Intrinsic chemoresistance of glioblastoma (GBM) is frequently owed to activation of the PI3K and MEK/ERK pathways. These signaling cascades are tightly interconnected however the quantitative contribution of both to intrinsic resistance is still not clear. Here, we aimed at determining the activation status of these pathways in human GBM biopsies and cells and investigating the quantitative impact of both pathways to chemoresistance. METHODS: Receptor tyrosine kinase (RTK) pathways in temozolomide (TMZ) treatment naive or TMZ resistant human GBM biopsies and GBM cells were investigated by proteome profiling and immunoblotting of a subset of proteins. Resistance to drugs and RTK pathway inhibitors was assessed by MTT assays. Apoptotic rates were determined by Annexin V staining and DNA damage with comet assays and immunoblotting. RESULTS: We analyzed activation of RTK pathways by proteome profiling of tumor samples of patients which were diagnosed a secondary GBM and underwent surgery and patients which underwent a second surgery after TMZ treatment due to recurrence of the tumor. We observed substantial activation of the PI3K and MEK/ERK pathways in both groups. However, AKT and CREB phosphorylation was reduced in biopsies of resistant tumors while ERK phosphorylation remained unchanged. Subsequent proteome profiling revealed that multiple RTKs and downstream targets are also activated in three GBM cell lines. We then systematically describe a mechanism of resistance of GBM cell lines and human primary GBM cells to the alkylating drugs TMZ and cisplatin. No specific inhibitor of the upstream RTKs sensitized cells to drug treatment. In contrast, we were able to restore sensitivity to TMZ and cisplatin by inhibiting PI3K in all cell lines and in human primary GBM cells. Interestingly, an opposite effect was observed when we inhibited the MEK/ERK signaling cascade with two different inhibitors. CONCLUSIONS: Temozolomide treatment naive and TMZ resistant GBM biopsies show a distinct activation pattern of the MEK/ERK and PI3K signaling cascades indicating a role of these pathways in resistance development. Both pathways are also activated in GBM cell lines, however, only the PI3K pathway seems to play a crucial role in resistance to alkylating agents and might serve as drug target for chemosensitization.

Impact of a detector dead time in phase-resolved Doppler analysis using spectral domain optical coherence tomography.

For any oblique sample movement containing a transverse velocity component, the commonly used linear relationship between the phase shift and the axial velocity component is erroneous for spectrometer-based optical coherence tomography (spectral domain OCT, SD-OCT). We recently proposed a new Doppler model that assumes a continuous integration of the photocurrent. In this research, we extend the model for detectors with a shutter control by taking detector dead time into account. We present the new relation between phase shift and oblique sample displacement as well as the correlation of the phases of consecutive depth scans, in dependency on the detector dead times ranging from 5% to 90%, as numerically calculated universal contour plots, which are valid for any center wavelength and sample beam size. We found that detector dead time is recommended, especially for oblique sample motion. The reason for this recommendation is the achieved linear relation between the phase shift and the axial velocity component in the velocity range relevant for in vivo measurements, despite the signal damping due to shorter exposure time of the line detector. The theoretical Doppler model is verified using a 1% Intralipid flow phantom model. Because of the results of this research, we believe future measurements in Doppler SD-OCT can be more simple and more accurate by setting a shutter control for the line detector used.

Relation of joint spectral and time domain optical coherence tomography (jSTdOCT) and phase-resolved Doppler OCT.

A variety of promising approaches for quantitative flow velocity measurement in OCT have been proposed in recent years. The question is: Which method gets the most precise flow velocity out of the interference signals detected. We have compared the promising joint spectral and time domain optical coherence tomography (jSTdOCT) and the commonly used phase-resolved Doppler OCT (DOCT) and describe the link between these two proven methods for OCT in the Fourier domain (FD OCT). First, we show that jSTdOCT can be significantly improved by calculating the center of gravity via an unbiased complex algorithm instead of detecting the maximum intensity signal of the broadened Doppler frequency spectrum. Secondly, we introduce a unified mathematical description for DOCT and jSTdOCT that differs only in one exponent and call it enhjSTdOCT. Third, we present that enhjSTdOCT has the potential to significantly reduce the noise of the velocity measurement by choosing an exponent depending on the transverse sample velocity component and the signal-to-noise ratio. EnhjSTdOCT is verified numerically and experimentally to find the optimal parameters for maximal velocity noise reduction.

Nutrition, lifestyle factors, and mental health in adolescents and young adults living in Austria.

BACKGROUND: Due to an alarming trend of overweight and obesity in children and adolescents, along with the sparse data on dietary habits and lifestyle factors, the present study aims to analyze the current nutritional behavior as well as the lifestyle and mental health of adolescents and young adults living in Austria. MATERIALS AND METHODS: In this cross-sectional study, a total of 500 respondents (aged between 14 and 24 years) completed an anonymous questionnaire on nutrition behavior, mental health, and lifestyle factors by Internet survey. RESULTS: Only 50% of the participants ate breakfast daily and 10% did not eat breakfast at all. About 47% of the respondents consumed milk and milk products daily. Furthermore, only 31% ate fruit and 21% ate vegetables at least once a day, and 46% ate fish seldom or never. Nearly 28% of young people liked to eat fast food twice or thrice a week and more, with males more often replacing a meal with a fast food product (36%) than females (21%). About 46% of the respondents engaged in physical activity only once a week (or more rarely). A fifth of our respondents (23%) spent more than 2 h a day using various social networks, with Facebook being the most popular social network among the respondents. Around 27% claimed to be smokers, with more female (33%) than male (20%) smoker. In terms of sleeping habits, 19% slept <6 h a day. Regarding well-being, 44% were more likely to feel stressed, 35% stated that they were tense, and 43% felt tired and listless. Eating together, physical activity, and sleep patterns showed positive effects on well-being, whereas higher consumption of fast food/snacks/soft drinks and alcoholic drinks/energy drinks was associated with relatively lower well-being. CONCLUSIONS: Unhealthy eating habits, suboptimal physical activity, and smoking are still prominent in a sample of Austrian adolescents and young people. In addition, stress and tiredness are also relevant problems in this collective.

Visualization of carious lesions with polarized and depolarized light microscopy.

Polarized light microscopy (PLM) is an established method in dental histology for investigating the ultrastructure and carious process of teeth. This study introduces a novel approach for measuring the degree of polarization (DOP) in a modified PLM setup and uses the DOP to assess the changes of the optical properties of enamel and dentin due to caries. The validation is provided by a comparison with complementary imaging methods, i.e. standard PLM and µCT. The results show that demineralization is reliably displayed by the DOP in accordance with the common imaging methods, and that this quantitative analysis of depolarization allows the characterization of the different pathohistological zones of caries.

Sulfonylureas exert antidiabetic action on adipocytes by inhibition of PPARγ serine 273 phosphorylation.

OBJECTIVE: Sulfonylureas (SUs) are still among the mostly prescribed antidiabetic drugs with an established mode of action: release of insulin from pancreatic ß-cells. In addition, effects of SUs on adipocytes by activation of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) have been described, which might explain their insulin-sensitizing potential observed in patients. However, there is a discrepancy between the impact of SUs on antidiabetic action and their rather moderate in vitro effect on PPARγ transcriptional activity. Recent studies have shown that some PPARγ ligands can improve insulin sensitivity by blocking PPARγ Ser-273 phosphorylation without having full agonist activity. It is unknown if SUs elicit their antidiabetic effects on adipocytes by inhibition of PPARγ phosphorylation. Here, we investigated if binding of SUs to PPARγ can interfere with PPARγ Ser-273 phosphorylation and determined their antidiabetic actions in vitro in primary human white adipocytes and in vivo in high-fat diet (HFD) obese mice. METHODS: Primary human white preadipocytes were differentiated in the presence of glibenclamide, glimepiride and PPARγ ligands rosiglitazone and SR1664 to compare PPARγ Ser-273 phosphorylation, glucose uptake and adipokine expression. Transcriptional activity at PPARγ was determined by luciferase assays, quantification of PPARγ Ser-273 phosphorylation was determined by Western blotting and CDK5 kinase assays. In silico modelling was performed to gain insight into the binding characteristics of SUs to PPARγ. HFD mice were administered SUs and rosiglitazone for 6 days. PPARγ Ser-273 phosphorylation in white adipose tissue (WAT), body composition, glucose tolerance, adipocyte morphology and expression levels of genes involved in PPARγ activity in WAT and brown adipose tissue (BAT) were evaluated. RESULTS: SUs inhibit phosphorylation of PPARγ at Ser-273 in primary human white adipocytes and exhibit a positive antidiabetic expression profile, which is characterized by up regulation of insulin-sensitizing and down regulation of insulin resistance-inducing adipokines. We demonstrate that SUs directly bind to PPARγ by in silico modelling and inhibit phosphorylation in kinase assays to a similar extend as rosiglitazone and SR1664. In HFD mice SUs reduce PPARγ phosphorylation in WAT and have comparable effects on gene expression to rosiglitazone. In BAT SUs increase UCP1 expression and reduce lipid droplets sizes. CONCLUSIONS: Our findings indicate that a part of SUs extra-pancreatic effects on adipocytes in vitro and in vivo is probably mediated via their interference with PPARγ phosphorylation rather than via classical agonistic activity at clinical concentrations.

In Vivo Thickness of the Healthy Tympanic Membrane Determined by Optical Coherence Tomography.

OBJECTIVE: Tympanic membrane (TM) thickness is an important parameter for differentiation between a healthy and a pathologic TM. Furthermore, it is needed for modeling the middle ear function. Endoscopic optical coherence tomography (eOCT) provides the opportunity to measure the TM thickness of the entire TM in vivo. MATERIALS AND METHODS: A total of 27 healthy ears were examined by eOCT. The system uses a light source with a central wavelength of 1,300 nm. The endoscope with an outer diameter of 3.5 mm provides a field of view of 10 mm and a working distance of 10 mm. Thickness measurements were carried out at 8 points on the TM. Additionally, the existing literature was analyzed, and a mean TM thickness value was determined. RESULTS: The mean thickness of the TM over all measurement points of the pars tensa was 120.2 µm, and the pars flaccida was significantly thicker with a mean thickness of 177.9 µm. Beyond that, there were no significant differences between the single quadrants. The mean TM thickness in the literature was 88.8 µm. DISCUSSION: EOCT provides the possibility for in vivo thickness determination of the TM. The mean thickness seems to be higher than in the previous studies, which were mostly carried out ex vivo. Our study takes the three-dimensional refraction into account and provides a method for the refraction correction.

Polarization-Sensitive Optical Coherence Tomography for Monitoring De- and Remineralization of Bovine Enamel In Vitro.

Early caries diagnosis still challenges dentistry. Polarization-sensitive optical coherence tomography (PS-OCT) is promising to detect initial lesions non-invasively in depth-resolved cross-sectional visualization. PS-OCT with determined degree of polarization (DOP) imaging provides an intuitive demineralization contrast. The aim of this study is to evaluate the suitability of DOP-based PS-OCT imaging to monitor controlled de- and remineralization progression for the first time and to introduce it as a valid, non-destructive in vitro detection method. Twelve standardized bovine enamel specimens were divided in different groups and demineralized with hydrochloric acid (HCl) as well as partly remineralized with fluoride over a 14-day pH-cycling experiment. The specimens were stored in artificial saliva and sodium chloride (NaCl), respectively. Progress measurements with PS-OCT were made with polarization-sensitive en faceand B-scan mode for qualitative evaluation. The specimens demineralized in HCl showed the most pronounced surface change (lowest DOP) and the most significant increase in depolarization. Additional fluoride treatment and the storage in artificial saliva resulted in the opposite (highest DOP). Therefore, DOP-based PS-OCT imaging appears to be a valuable technique for visualization and monitoring of enamel demineralization and remineralization processes in vitro. However, these findings need to be confirmed in human teeth ex vivo or in situ.

Characteristics of Clinically Classified Oral Lichen Planus in Optical Coherence Tomography: A Descriptive Case-Series Study.

Malignant transformation of oral lichen planus (OLP) into oral squamous cell carcinoma is considered as one of the most serious complications of OLP. For the early detection of oral cancer in OLP follow-up, accurate localization of the OLP center is still difficult but often required for confirmatory biopsy with histopathological examination. Optical coherence tomography (OCT) offers the potential for more reliable biopsy sampling in the oral cavity as it is capable of non-invasively imaging the degenerated oral layer structure. In this case-series study with 15 patients, features of clinically classified forms of OLP in OCT cross-sections were registered and correlated with available histologic sections. Besides patients with reticular, atrophic, erosive and plaque-like OLP, two patients with leukoplakia were included for differentiation. The results show that OCT yields information about the epithelial surface, thickness and reflectivity, as well as the identifiability of the basement membrane and the vessel network, which could be used to complement the visual clinical appearance of OLP variants and allow a more accurate localization of the OLP center. This forms the basis for further studies on OCT-assisted non-invasive clinical classification of OLP, with the aim of enabling decision support for biopsy sampling in the future.

Severity of childhood maltreatment predicts reaction times and heart rate variability during an emotional working memory task in borderline personality disorder.

Background: Difficulties in emotion regulation are a core symptom of borderline personality disorder (BPD) and often interfere with cognitive functions, such as working memory (WM). Traumatic childhood experiences, including severe maltreatment, can contribute to emotion dysregulation, possibly mediated by changes in high-frequency heart rate variability (HF-HRV). However, it is not yet entirely understood if HF-HRV alterations underlie impaired WM during emotional distraction in BPD and if this is related to traumatic childhood experiences and to comorbid post-traumatic stress disorder (PTSD). Objective: Our aim was to investigate performance (reaction times, RTs) and HF-HRV during an emotional working memory task (EWMT) in relation to childhood maltreatment severity and comorbid PTSD in BPD. Method: Eighty-one women (n = 28 healthy controls (HC) and n = 53 BPD patients of which n = 18 had comorbid PTSD) performed an adapted Sternberg item recognition WM task with neutral and negative social cues (interpersonal scenes from the International Affective Picture System (IAPS), and neutral, fearful, and angry faces) as distractors. Dependent variables were RTs of correct trials and HF-HRV. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire. Results: Compared to healthy participants, patients with BPD showed prolonged RTs across all distractor conditions with social cues, regardless of their emotional valence. Patients with BPD, especially those with PTSD, demonstrated reduced HF-HRV both at rest and during EWMT. Severity of childhood maltreatment predicted longer RTs and lower HF-HRV during the EWMT. Conclusions: Findings suggest that adverse childhood experiences accelerate difficulties in shifting attention away from social information and that these are more pronounced in individuals with BPD. Reduced HF-HRV (low parasympathetic-tonus) may be an important psychophysiological mechanism underlying impaired WM in the presence of distracting social cues in patients with BPD, especially in those with comorbid PTSD. HIGHLIGHTS: This study provides evidence that childhood maltreatment experiences are associated with hypersensitivity to social information and reduced high-frequency heart rate variability during a working memory task in borderline personality disorder.

Antecedentes: las dificultades en la regulación emocional es un síntoma central del trastorno límite de la personalidad (TLP) y, a menudo, interfieren con las funciones cognitivas, como la memoria de trabajo (MT). Las experiencias traumáticas de la infancia, incluido el maltrato grave, pueden contribuir a la desregulación emocional, posiblemente mediada por cambios en la variabilidad de la frecuencia cardíaca de alta frecuencia (VFC-AF). Sin embargo, aún no se comprende del todo si las alteraciones de VFC-AF subyacen a la alteración de la MT durante la distracción emocional en el TLP y si esto está relacionado con experiencias traumáticas de la infancia y con el trastorno de estrés postraumático (TEPT) comórbido.Objetivo: Nuestro objetivo fue investigar el rendimiento (tiempos de reacción, TR) y VFC-AF durante una tarea de memoria de trabajo emocional (MTE) en relación con la gravedad del maltrato infantil y el TEPT comórbido en el TLP.Método: Ochenta y una mujeres (n=28 controles sanos (CS) y n=53 pacientes con TLP, de las cuales n=18 tenían TEPT comórbido) realizaron una tarea de MT de reconocimiento de elementos de Sternberg adaptada con señales sociales neutras y negativas (escenas interpersonales del Sistema internacional de imágenes afectivas (IAPS por sus siglas en ingles) y rostros neutrales, temerosos y enojados) como distractores. Las variables dependientes fueron TR de ensayos correctos y VFC-AF. El maltrato infantil se evaluó con el Cuestionario de Trauma Infantil.Resultados: En comparación con las participantes sanas, las pacientes con TLP mostraron TR prolongados en todas las condiciones de distracción con señales sociales, independientemente de su valencia emocional. Los pacientes con TLP, especialmente aquellos con TEPT, demostraron una reducción de VFC-AF tanto en reposo como durante MTE. La gravedad del maltrato infantil predijo TR más largos y VFC-AF más bajo durante el MTE.Conclusiones: Los resultados sugieren que las experiencias infantiles adversas refuerzan las dificultades para desviar la atención de la información social y que estas son más pronunciadas en las personas con TLP. La VFC-AF reducida (tono parasimpático bajo) puede ser un mecanismo psicofisiológico importante subyacente a la MT alterada en presencia de señales sociales que distraen en pacientes con TLP, especialmente en aquellos con TEPT comórbido.

Improving patient pathways for systemic lupus erythematosus: a multistakeholder pathway optimisation study.

OBJECTIVE: Among the most significant challenges in SLE are the excessive diagnosis delay and the lack of coordinated care. The aim of the study was to investigate patient pathways in SLE in order to improve clinical and organisational challenges in the management of those with suspected and confirmed SLE. METHODS: We conducted a cross-sectional study of patients with SLE, healthcare providers and other representative stakeholders. Focus groups were conducted, and based on the collected data the most impactful disruption points in SLE patient pathways were identified. A novel framework to improve individual patient pathways in SLE was developed, discussed and validated during a consensus meeting with representative stakeholders. RESULTS: Six thematic clusters regarding disruption in optimal patient pathways in SLE were identified: appropriate and timely referral strategy for SLE diagnosis; the need for a dedicated consultation during which the diagnosis of SLE would be announced, and following which clarifications and psychological support offered; individualised patient pathways with coordinated care based on organ involvement, disease severity and patient preference; improved therapeutic patient education; prevention of complications such as infections, osteoporosis and cancer; and additional patient support. During the consensus meeting, the broader panel of stakeholders achieved consensus on these attributes and a framework for optimising SLE patient pathways was developed. CONCLUSIONS: We have identified significant disruption points and developed a novel conceptual framework to improve individual patient pathways in SLE. These data may be of valuable interest to patients with SLE, their physicians, health organisations as well as policy makers.

A Handheld Fiber-Optic Probe to Enable Optical Coherence Tomography of Oral Soft Tissue.

This study presents a highly miniaturized, handheld probe developed for rapid assessment of soft tissue using optical coherencetomography (OCT). OCT is a non-invasive optical technology capable of visualizing the sub-surface structural changes that occur in soft tissue disease such as oral lichen planus. However, usage of OCT in the oral cavity has been limited, as the requirements for high-quality optical scanning have often resulted in probes that are heavy, unwieldy and clinically impractical. In this paper, we present a novel probe that combines an all-fiber optical design with a light-weight magnetic scanning mechanism to provide easy access to the oral cavity. The resulting probe is approximately the size of a pen (10 mm × 140 mm) and weighs only 10 grams. To demonstrate the feasibility and high image quality achieved with the probe, imaging was performed on the buccal mucosa and alveolar mucosa during routine clinical assessment of six patients diagnosed with oral lichen planus. Results show the loss of normal tissue structure within the lesion, and contrast this with the clear delineation of tissue layers in adjacent inconspicuous regions. The results also demonstrate the ability of the probe to acquire a three-dimensional data volume by manually sweeping across the surface of the mucosa. The findings of this study show the feasibility of using a small, lightweight probe to identify pathological features in oral soft tissue.

Optical coherence tomography in biomedical research.

Optical coherence tomography (OCT) is a noninvasive, high-resolution, interferometric imaging modality using near-infrared light to acquire cross-sections and three-dimensional images of the subsurface microstructure of biological specimens. Because of rapid improvement of the acquisition speed and axial resolution of OCT over recent years, OCT is becoming increasingly attractive for applications in biomedical research. Therefore, OCT is no longer used solely for structural investigations of biological samples but also for functional examination, making it potentially useful in bioanalytical science. The combination of in vivo structural and functional findings makes it possible to obtain thorough knowledge on basic physiological and pathological processes. Advanced applications, for example, optical biopsy in visceral cavities, have been enabled by combining OCT with established imaging modalities. This report gives an outline of the state of the art and novel trends of innovative OCT approaches in biomedical research in which the main focus is on applications in fundamental research and pre-clinical utilization.

Does DDI-Predictor Help Pharmacists to Detect Drug-Drug Interactions and Resolve Medication Issues More Effectively?

The characterization of drug-drug interactions (DDIs) may require the use of several different tools, such as the thesaurus issued by our national health agency (i.e., ANSM), the metabolic pathways table from the Geneva University Hospital (GUH), and DDI-Predictor (DDI-P). We sought to (i) compare the three tools' respective abilities to detect DDIs in routine clinical practice and (ii) measure the pharmacist intervention rate (PIR) and physician acceptance rate (PAR) associated with the use of DDI-P. The three tools' respective DDI detection rates (in %) were measured. The PIRs and PARs were compared by using the area under the curve ratio given by DDI-P (RAUC) and applying a chi-squared test. The DDI detection rates differed significantly: 40.0%, 76.5%, and 85.2% for ANSM (The National Agency for the Safety of Medicines and Health Products), GUH and DDI-P, respectively (p < 0.0001). The PIR differed significantly according to the DDI-P's RAUC: 90.0%, 44.2% and 75.0% for RAUC ≤ 0.5; RAUC 0.5-2 and RAUC > 2, respectively (p < 0.001). The overall PAR was 85.1% and did not appear to depend on the RAUC category (p = 0.729). Our results showed that more pharmacist interventions were issued when details of the strength of the DDI were available. The three tools can be used in a complementary manner, with a view to refining medication adjustments.

Prescribing practices of lopinavir/ritonavir, hydroxychloroquine and azithromycin during the COVID-19 epidemic crisis and pharmaceutical interventions in a French teaching hospital.

OBJECTIVE: The aims of this study were to describe prescribing practices of lopinavir/ritonavir, hydroxychloroquine and azithromycin during the COVID-19 epidemic crisis (primary endpoint), then to characterise pharmaceutical interventions (PIs) targeted to these medications and evaluate the impact of these PIs on prescribers' practices (secondary end-points). METHODS: This retrospective observational study was carried out at the University Hospital of Strasbourg (France) from March to April 2020. The analysed population excluded patients from intensive care units but included all other adult patients with COVID-19 who received at least one dose of lopinavir/ritonavir combination, hydroxychloroquine or azithromycin, while inpatients. Analyses were performed by using data extracted from electronic medical records. RESULT: During the study period, 278 patients were included. A rapid decrease in lopinavir/ritonavir prescriptions was observed. This was accompanied by an increase in hydroxychloroquine and azithromycin prescriptions until the end of March, followed by a decrease leading to the disappearance of these two medications in April. The pharmaceutical analysis of the prescriptions resulted in 59 PIs of which 21 were associated with lopinavir/ritonavir, 32 with hydroxychloroquine and 6 with azithromycin. Regarding the medication-related problems, the most frequent ones were incorrect treatment durations (n=32 (54.2%)), drug interactions with potential torsadogenic reactions (n=14 (23.7%)) and incorrect dosing (n=6 (10.2%)). From the 59 PIs, 48 (81.4%) were accepted and physicians adjusted the medication regimens in a timely manner. CONCLUSION: This study demonstrated the value-even more meaningful in a crisis situation-of a strong synergy between physicians and pharmacists for patient-safety focused practices.

In Vivo Endoscopic Optical Coherence Tomography of the Healthy Human Oral Mucosa: Qualitative and Quantitative Image Analysis.

To date, there is still a lack of reliable imaging modalities to improve the quality of consultation, diagnostic and medical examinations of the oral mucosa in dentistry. Even though, optical technologies have become an important element for the detection and treatment of different diseases of soft tissue, for the case of oral screenings the evidence of the benefit in comparison to conventional histopathology is mostly still pending. One promising optical technology for oral diagnostics is optical coherence tomography (OCT). To prove the potential of OCT, even the amount of freely accessible OCT data is not sufficient to describe the variance of healthy human oral soft tissue in vivo. In order to remedy this deficiency, the present study provides in vivo OCT cross sections of the human oral mucosa of the anterior and posterior oral cavity as well as the oropharynx of 47 adult volunteers. A collection of representative OCT cross sections forms the basis for a randomized blinded image analysis by means of seven criteria to assess the main features of the superficial layers of the human oral mucosa and to determine its correlation to regional features known from hematoxylin and eosin (HE) stained histology.

Immunosuppressive agents for rheumatoid arthritis: a systematic review of clinical trials and their current development stage.

AIMS: With the arrival of conventional synthetic (csDMARDs), biological (bDMARDS) and then targeted synthetic (tsDMARDs) disease-modifying anti-rheumatic drugs, the therapeutic arsenal against rheumatoid arthritis (RA) has recently expanded. However, there are still some unmet needs for patients who do not achieve remission and continue to worsen despite treatments. Of note, most randomized controlled trials show that, for methotrexate-inadequate responders, only 20% of patients are ACR70 responders. With our better understanding of RA pathogenesis, finding new treatments is a necessary challenge. The objective of our study was to analyse the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development. METHODS: We conducted a systematic review of all drugs in clinical development in RA, in 17 online registries of clinical trials. RESULTS: The search yielded 4652 trials, from which we identified 243 molecules. Those molecules belong to csDMARDs (n = 22), bDMARDs (n = 118), tsDMARDs (n = 103). Twenty-four molecules are already marketed in RA in at least one country: eight csDMARDs, 10 bDMARDs and six tsDMARDs. Molecules under current development are mainly bDMARDs (n = 34) and tsDMARDs (n = 33). Seven of those have reached phase III. A large number of molecules (150/243, 61.7%) have been withdrawn. CONCLUSION: Despite the availability of 24 marketed molecules, the development of new targeted molecules is ongoing with a total of 243 molecules in RA. With seven molecules currently reaching phase III, we can expect an increase in the armamentarium in the years to come.