Notes

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5; p<0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events.

Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).
Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).
Minigenes and in silico prediction tools are commonly used to assess the impact on splicing of CFTR variants. Exon skipping is often neglected though it could impact the efficacy of targeted therapies. The aim of the study was to identify exon skipping associated with CFTR variants and to evaluate in silico predictions of seven freely available software.

CFTR basal exon skipping was evaluated on endogenous mRNA extracted from non-CF nasal cells and on two CFTR minigene banks. In silico tools and minigene systems were used to evaluate the impact of CFTR exonic variants on exon skipping.

Data showed that out of 65 CFTR variants tested, 26 enhanced exon skipping and that in silico prediction efficacy was of 50%-66%. Some in silico tools presented predictions with a bias towards the occurrence of splicing events while others presented a bias towards the absence of splicing events (non-detection including true negatives and false negatives). Classification of exons depending on their basal exon skipping level increased prediction rates up to 80%.

This study indicates that taking basal exon skipping into account could orientate the choice of the in silico tools to improve prediction rates. It also highlights the need to validate effects using in vitro assays or mRNA studies in patients. Eventually, it shows that variant-guided therapy should also target exon skipping associated with variants.
This study indicates that taking basal exon skipping into account could orientate the choice of the in silico tools to improve prediction rates. It also highlights the need to validate effects using in vitro assays or mRNA studies in patients. Eventually, it shows that variant-guided therapy should also target exon skipping associated with variants.Aminoglycosides are commonly used to treat infections in CF patients and are highly ototoxic. The incidence of tobramycin-induced hearing loss, tinnitus, vertigo or dizziness (ototoxicity) varies widely from 0 to 56% secondary to variation in patient enrollment, dosing, audiometry, and ototoxic criteria. The aim of this study is to determine the incidence of ototoxicity after one course of once-daily IV tobramycin in CF patients. Adult CF patients with acute pulmonary exacerbations were enrolled on IV tobramycin (10 mg/kg/d, ≥10 days). Pure-tone audiometry was performed for standard and extended high frequencies in the sensitive range for ototoxicity (SRO). American-Speech-Language-Hearing-Association cochleotoxicity criteria were applied. Distortion product otoacoustic emissions (DPOAE) and the words-in-noise-test (WINT) were assessed. Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS) were used. Eighteen CF patients, mean age 31.1 (18-59), were enrolled. The incidence of cochleotoxic change from baseline at 2 and 4 weeks post-treatment was 89% and 93%. For DPOAE, a measure of outer hair-cell function, the incidence of ≥5 dB decrease was 82% and 80%. For WINT, a measure of word recognition, the incidence of ≥10% decrease was 17% and 40%. For TFI, the incidence of ≥10pt increase was 12% and 8%, and for VSS, the incidence of ≥6pt increase was 0% and 8%. One course of IV tobramycin was sufficient to cause hearing loss and other ototoxic symptoms four weeks after treatment ended. Audiometric measures were more sensitive to ototoxic change than TFI & VSS. Age and duration of tobramycin treatment were not obvious factors for predicting ototoxicity.
We tested if disrupting iron utilisation by P. aeruginosa by adding the Tris-buffered chelating agent CaEDTA to nebulised tobramycin would enhance bacterial clearance and improve lung function in CF patients.

In this double-blind, randomised controlled trial, 26 episodes (25 patients) with P. aeruginosa infection admitted to two CF centres for treatment of an acute pulmonary exacerbation were randomly assigned to receive either 75mg CaEDTA in Tris-buffered saline or placebo (Tris-buffered saline) nebulised in combination with 250mg tobramycin twice daily for six weeks followed with four week safety follow-up. Primary endpoints were safety, tolerability, and bacterial density of P. aeruginosa. A secondary endpoint was lung function.

The study drug was well tolerated with adverse events comparable in both groups. The mean (SD) reduction in sputum P. aeruginosa count (log
CFU/g) in the CaEDTA vs placebo group was 2·05 (2·57) vs 0·82 (2·71) at two weeks relative to admission (p=0·39). The mean improvement in ppFEV
was 16vs 5 (p=0·16); 11vs 2 (p=0·28); and 6vs 2 percentage points (p=0·47) at two, six, and ten weeks in CaEDTA and placebo groups, respectively.

In this pilot study in CF patients, an increase in the reduction of sputum density of P. aeruginosa and an increase in ppFEV
was observed in the group of patients who received Tris-CaEDTA added to inhaled tobramycin compared to the group who received inhaled tobramycin alone, although these differences were not statistically significant. The treatment was also shown to be safe.
In this pilot study in CF patients, an increase in the reduction of sputum density of P. aeruginosa and an increase in ppFEV1 was observed in the group of patients who received Tris-CaEDTA added to inhaled tobramycin compared to the group who received inhaled tobramycin alone, although these differences were not statistically significant. The treatment was also shown to be safe.
In recent years, telemedicine has gained increasing importance in the delivery of pharmaceutical care. The use of video technologies for remote communication between different parties offers the potential to meet the future challenges which arise from the increase in elderly and chronically ill patients. However, the influence of these technologies on patient-related outcomes in pharmaceutical care is not yet sufficiently known.

In December 2018 a systematic literature search was conducted in the databases Medline, Cochrane Library and PubPharm. see more Randomized controlled trials were considered, which investigate real-time video conferencing between pharmacists on the one hand and patients or other healthcare providers on the other hand. The influence on patient related outcomes compared to standard care was assessed. The bias potential was evaluated using the Cochrane Risk-of-Bias instrument. A total of 4 randomized controlled trials could be included.

The studies describe partly complex intervention settin
Prescribing errors are prevalent in hospital settings with provision of feedback recommended to support prescribing of doctors. link2 Feedback on prescribing has been described as feasible and valued but limited by doctors, with pharmacists described as credible facilitators of prescribing feedback. link3 Evidence supporting prescribing feedback has been limited to date. A formalised programme of pharmacist-led prescribing error feedback was designed and implemented to support prescribers.

To evaluate the impact of a prescribing feedback intervention on prescribing error rates and frequency of prescribing error severity and type.

Prospective prescribing audits were undertaken across sixteen hospital wards in a UK teaching hospital over a five day period with 36 prescribers in the intervention group and 41 in the control group. The intervention group received pharmacist-led, individualised constructive feedback on their prescribing, whilst the control group continued with existing practice. Prescribing was re-auditebing feedback has the potential to reduce prescribing errors and improve prescribing outcomes and patient safety.
Previous studies have suggested that children with developmental coordination disorder (DCD) rely heavily on vision to perform movements, which may contribute to their clumsy movements. However, few studies have objectively and quantitatively investigated the perceptual biases of children with DCD.

A visual-tactile temporal order judgment (TOJ) task was used to measure and compare the perceptual biases of 19 children with DCD and 19 age- and sex-matched typically developing children. The point of subjective equality, which demonstrates when "visual first" and "tactile first" judgment probabilities are equal (50%), obtained by analyzing the results of the visual-tactile TOJ task, was used as an indicator of perceptual biases. Further, variables (age and manual dexterity in all participants; motor function, autism spectrum disorder and attention-deficit hyperactivity disorder traits, and depressive symptoms in children with DCD) associated with perceptual biases were examined with correlation analysis.

Children with DCD had significantly stronger visual bias than typically developing children. Overall correlation analysis showed that increased visual bias was significantly correlated with poor manual dexterity.

Children with DCD had a strong visual bias, which was associated with poor manual dexterity.
Children with DCD had a strong visual bias, which was associated with poor manual dexterity.
Sleep loss results in state instability of cognitive functioning. It is not known whether this effect is more expressed when there is an increased cognitive demand. Moreover, while vulnerability to sleep loss varies substantially among individuals, it is not known why some people are more affected than others. We hypothesized that top-down regulation was specifically affected by sleep loss and that subclinical inattention and emotional instability traits, related to attention-deficit/hyperactivity disorder symptoms, predict this vulnerability in executive function and emotion regulation, respectively.

Healthy subjects (ages 17-45 years) rated trait inattention and emotional instability before being randomized to either a night of normal sleep (n= 86) or total sleep deprivation (n= 87). Thereafter, they performed a neutral and emotional computerized Stroop task, involving words and faces. Performance was characterized primarily by cognitive conflict reaction time and reaction time variability (RTV), mirror that less stable performance in executive functioning may surface after sleep loss in vulnerable individuals characterized by subclinical symptoms of inattention.
Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.

Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.

A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.
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