Medicines and other factors causing deaths in English and welsh care homes: five-years of preventing future death reports by coroners.

BACKGROUND: Whilst information has been published on the impact, severity and causes of incidents involving medicines in care homes, it has not been systematically described. This review explored whether coroners' Preventing Future Death (PFD) reports involving medicines for people living in care homes could add to this evidence base. METHODS: PFD reports made publicly available between 2017 and 2021 classified as 'care home-related deaths' were reviewed. Reports describing medicines and/or medicines processes were identified. Contributory factors within these reports were then identified. RESULTS: Within the timeframe, 156 reports were published, and 25 described medicines (n = 27) or medicines processes (n = 5) concerning people living in care homes. The impact of medicines and/or medicines processes was quantified as no impact (n = 7), contributory (n = 6) and direct (n = 14) per report. Two key themes emerged. Four deaths had an association between their falls risk, prescribed anticoagulants, and the failure of the service to seek timely emergency care following a fall and two deaths concerned endocrine medicines, where people refused insulin or blood sugar monitoring and staff did not seek timely advice. CONCLUSION: This study demonstrated PFD reports provide an insight into the potential association between medicines, and other aspects of the person's care in causing harm.

The relationship between the pharmacist's role, patient understanding and satisfaction during the provision of a cost-effective pharmacist-led intervention.

RATIONALE, AIMS AND OBJECTIVES: This study aimed to investigate the relationship between the pharmacist's role, patient understanding and satisfaction during the provision of a cost-effective pharmacist-led intervention using structural equation modelling (SEM). SEM is a group of statistical techniques used in different disciplines to model latent variables and evaluate theories. METHODS: A validated questionnaire was used to gather patient views on a pharmacist-led intervention. A conceptual model was developed to test the statistical significance of the relationship between patient understanding and satisfaction, the pharmacist's role and patient understanding, the pharmacist's role and patient satisfaction. In addition, the study evaluated the model's in-sample and out-of-sample predictive power. The analysis tested fours hypotheses (H): 1) There was no significant relationship between patient understanding and patient satisfaction; 2) There was no significant relationship between the pharmacist's role and patient understanding; 3) There was no significant relationship between the pharmacist's role and patient satisfaction; 4) The in-sample and out-of-sample predictive power of the model. Data were analysed using Smart-PLS software version 3.2.8. RESULTS: Two hundred and forty-six patients returned the questionnaire. Construct reliability, validity (Cronbach's alpha〉0.70, ⍴A>0.70, ⍴C>0.70), average extracted variance (AVE〉0.50) and discriminant validity (HTMT<0.85) were confirmed. The structural model and hypothesis testing results showed that all hypotheses were supported in this study. Path coefficients and effect sizes suggested that the pharmacist's role played a significant part in patient understanding (H2, ß=0.650, f2 =0.730, p<0.001), which then influenced patient satisfaction (H1, ß=0.474, f2 =0.222, p<0.001). The in-sample and out-of-sample predictive powers were moderate. CONCLUSIONS: Patient satisfaction is becoming an integral component in healthcare provision and evaluation of healthcare quality. The results support using structural equation modelling to assess the link between the pharmacist's role and patient understanding and satisfaction when delivering cost-effective pharmacist-led interventions.

Evaluation of the effectiveness of the Super Enhanced Single Vision Lens 01 (SESL01) in reducing symptoms of computer vision syndrome (CVS): A study protocol for a double-blind, two-arm parallel randomized controlled trial.

BACKGROUND: The increased use of digital devices has implications for health and, particularly, the eyes, due to Computer Vision Syndrome (CVS). Millions of individuals of all ages are at risk of CVS, and its prevalence ranges from 25% to 93%. This trial will evaluate the effectiveness of the Super Enhanced Single Vision Lens 01 (SESL01) versus standard single vision lens in reducing symptoms of CVS assessed by the Computer Vision Syndrome Questionnaire (CVS-Q®) scores. METHOD: A double-blind, two-arm parallel randomized controlled trial will be conducted at the University of Central Lancashire, Preston (UK), recruiting students and staff with CVS-Q score ≥ 6. A 1:1 randomization and a sample size of 300 participants will be sufficient to detect a 2-point difference in the CVS-Q score between the intervention and control groups with an alpha of 5%, two-sided, allowing for a dropout of 10%. The control group will use standard single vision lenses, and the intervention group SESL01. The primary outcome to week 14 will be the difference in the CVS-Q score between SESL01 and standard single vision lenses. Secondary outcomes include the percentage of participants with CVS-Q score < 6 (no symptoms) and CVS-Q score ≥ 6 (symptoms) in the SESL01 and the standard single vision group at weeks 6, 10 and 14; the percentage of participants in each group with a total CVS-Q score < 6, 6-12, 13-19, and ≥ 20 at weeks 6, 10 and 14. The primary analysis will be the intention to treat. DISCUSSION: Findings may inform decisions about adopting the SESL01 lenses to reduce CVS. TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT05545878. Registered: Sept. 19, 2022.

Primate-specific transposable elements shape transcriptional networks during human development.

The human genome contains more than 4.5 million inserts derived from transposable elements (TEs), the result of recurrent waves of invasion and internal propagation throughout evolution. For new TE copies to be inherited, they must become integrated in the genome of the germline or pre-implantation embryo, which requires that their source TE be expressed at these stages. Accordingly, many TEs harbor DNA binding sites for the pluripotency factors OCT4, NANOG, SOX2, and KLFs and are transiently expressed during embryonic genome activation. Here, we describe how many primate-restricted TEs have additional binding sites for lineage-specific transcription factors driving their expression during human gastrulation and later steps of fetal development. These TE integrants serve as lineage-specific enhancers fostering the transcription, amongst other targets, of KRAB-zinc finger proteins (KZFPs) of comparable evolutionary age, which in turn corral the activity of TE-embedded regulatory sequences in a similarly lineage-restricted fashion. Thus, TEs and their KZFP controllers play broad roles in shaping transcriptional networks during early human development.

Medication errors and processes to reduce them in care homes in the United Kingdom: a scoping review.

Medicines-related incidents are a leading cause of preventable harm across all patient groups, including care home residents. Despite national guidance, there is little information on assessing medication error rates and evaluating changes to reduce them. This review explored the scientific and gray literature on medicine-related incidents, causation and evaluation of changes in care homes in the United Kingdom. The research identified 2951 documents, 32 analyzed; some of them covered more than one area. Seven reported rate and causes, eleven causes, eleven made recommendations, and four reported the evaluation of changes to processes and systems. Three areas emerged; 1) medicine-related incident rates ranged between 1% and 38%, 2) incident rates increased where formulations were not tablets or capsules ranging from 12% to 50% depending on the formulation, 3) three evaluations of changes aimed at reducing medicine incidents. Therefore, information on medicine-related incidents in care homes is available, but not systematically described.

Spoken propositional idea density, a measure to help second language English speaking students: A multicentre cohort study.

PURPOSE: Idea density has been shown to influence comprehension time for text in various populations. This study aims to explore the influence of spoken idea density on attainment in young, healthy subjects using demographic characteristics. METHODS: Students watched two online lectures and answered 10 multiple choice questions on them. Students received one more idea dense (MID) and one less idea dense (LID) lecture on two different subjects. RESULTS: Seventy-five students completed the study achieving a higher median score after a less idea-dense lecture (LID = 7(3), MID = 6(3), p = 0.04). Artificial neural network models revealed the first language as the main predictor of exam performance. The odds ratio (OR) of obtaining ≥70% after a more idea-dense lecture was six-time higher for the first language versus second language English speakers (OR = 5.963, 95% CI 1.080-32.911, p = 0.041). The odds ratio was not significant when receiving a less dense lecture (OR = 2.298, 95% CI 0.635-8.315, p = 0.205). Second-language speakers benefited from receiving a lower idea density, achieving a 10.8% score increase from high to low density, versus a 3.2% increase obtained by first language speakers. CONCLUSIONS: The propositional idea density of lectures directly influences students' comprehension, and disproportionately for second language speakers; revealing the possibility of reduced spoken idea density in levelling the attainment differential between first and second language speakers.

Evaluation of students' performance and engagement using post-laboratory integrated assessments within a pharmacy course in the United Kingdom: a pilot cohort cross-over study.

INTRODUCTION: This pilot study investigated the impact of practice integrated, post-laboratory assessment on the scientific education and attitudes of first-year pharmacy students. Median assessment performance, achievement of full marks, and engagement in laboratory classes were evaluated. METHODS: The pilot randomised cross-over study was conducted at the University of Central Lancashire. Students were randomly assigned to two groups, and after undertaking four identical pharmaceutics laboratory classes, answered two science-based questions that were either integrated with practice using a contextualizing scenario or had no integration. Student performance and engagement were subsequently analysed. RESULTS: Thirty students completed the study. Students performed better in the integrated assessment (median 3.5; interquartile range [IQR] 2.00-4.00) compared to the non-integrated assessment (median 2; IQR 1.75-3.00) (P < .001). Twenty-five students (83%) achieved full marks with the integrated assessment (P = .006). Correlation (R2) for the integrated assessment was 0.90 and for the non-integrated assessment was 0.12. Engagement was positive in both groups but significantly improved in the domains of "instructor contribution" and "value of activity" (P = .01) when receiving the integrated assessment. CONCLUSIONS: Integrated and contextualized assessment of science teaching as a lone intervention increased pharmacy students' performance and engagement in laboratory classes without requiring any change to the teaching session itself.

Pedagogic Interest Group: a novel and proven collaborative, adhocracy research group structure.

This article was migrated. The article was marked as recommended. Background: Teaching is a core activity for universities, and pedagogic research is essential for improving student experience, staff satisfaction, and research and teaching quality. Pedagogic research is often performed as a secondary research area or by part-time staff, requiring good collaboration. Existing research structures in universities often result in pedagogic research falling through the gaps and for quality work and pedagogic improvements to be missed. Aim: The aim was to develop a clear and flexible structure to improve participation and output of pedagogic research in the School of Pharmacy and Biomedical Sciences at the University of Central Lancashire. Method: A collaborative adhocracy called the Pedagogic Interest Group (PIG) was created in January 2020. It was designed to allow collaborative, flexible research projects to be easily set up by any staff member. The group supervises and organises a bespoke team of people for each project, drawing on all previously involved staff's expertise and contacts through an initial project meeting organised by an independent group chair. Each project group runs independently, with further help available from the group chairs. Results: Under the PIG structure, seven projects have been undertaken in less than one year. Two papers were published, one under review, two in preparation, one abstract accepted at an international conference, and fifteen funded undergraduate research projects completed. Part-time teaching staff are more involved in the research. Internally, three departments and externally, three other UK universities have been collaboratively involved in research projects. Conclusion: The PIG structure works and depends on staff's continued engagement and at least two independent chairs for impartiality and transparency.

Patient as teacher sessions contextualize learning, enhancing knowledge, communication, and participation of pharmacy students in the United Kingdom.

PURPOSE: This study aimed to evaluate the impact of Patient As Teacher (PAT) sessions on the knowledge, communication skills, and participation of pharmacy students in the United Kingdom. METHODS: During the academic year 2019-2020, year 1 and 2 pharmacy students at the University of Central Lancashire were invited to complete a questionnaire following PAT sessions. Data were analyzed by means of descriptive statistics, including mean and standard deviation (SD) for: continuous variables and reliability analysis. Pearson's Chi-Square or Fisher Exact Test, odds ratio, and Phi were used for analyzing dichotomous variables. Thematic analysis was used for free text comments. RESULTS: Sixty eight of 228 students participated, (response rate of 29.8%). No statistical difference was found between gender (p=0.090); a statistically significant difference was found between year (p=0.008). Cronbach's alpha (0.809) confirmed a good internal consistency. 97.0% of the students learned a lot, and 85.3% appreciated and valued the PAT sessions; 89.7% wanted more sessions. 92.7% perceived the sessions to contextualize their learning. Five questions were dichotomized by grouping the responses into negative and positive; 90.3% of responses were positive and did not show statistically significant differences in gender and year of study. Overall students' free text comments were positive, but active listening and consultation appeared in the positive and negative domains, highlighting the need for more student engagement. CONCLUSIONS: PAT sessions had a positive impact on students' knowledge, communication skills, and participation, and contextualized learning. They provide a valuable contribution to the pharmcy students' experience in the United Kingdom.

A conceptual model for students' satisfaction with team-based learning using partial least squares structural equation modelling in a faculty of life sciences, in the United Kingdom.

PURPOSE: Students' satisfaction is an essential element in higher education. This study aimed to identify paths and predictive power of students' satisfaction during team-based learning (TBL) activities in the faculty of life sciences using partial least squares structural equation modelling (PLS-SEM). METHODS: In 2018-2019, at the University of Sussex (Falmer, UK), 180 life science students exposed to TBL were invited to participate in the study. Team-Based-Learning-Student-Assessment-Instrument was used. A conceptual model was developed for testing six hypotheses. H1: What was the effect of TBL on student satisfaction? H2: What was the effect of lectures on student satisfaction? H3: What was the effect of TBL on accountability? H4: What was the effect of lectures on accountability? H5: What was the effect of accountability on student satisfaction? H6: What were the in-sample and out-of-sample predictive power of the model? The analysis was conducted using the PLS-SEM approach. RESULTS: Ninety-nine students participated in the study giving a 55% response rate. Confirmatory tetrad analysis suggested a reflective model. Construct reliability, validity, average extracted variance, and discriminant validity were confirmed. All path coefficients were positive, and 5 were statistically significant (H1: ß=0.587, P<0:001; H2: ß=0.262, P<0.001; H3: ß=0.532, P<0.001; H4: ß=0.063, P=0.546; H5: ß=0.200, P=0.002). The in-sample predictive power was weak for Accountability, (R2=0.303; 95% confidence interval [CI], 0.117-0.428; P<0.001) and substantial for Student Satisfaction (R2=0.678; 95% CI, 0.498-0.777; P<0.001). The out-of-sample predictive power was moderate. CONCLUSION: The results have demonstrated the possibility of developing and testing a TBL conceptual model using PLS-SEM for the evaluation of path coefficients and predictive power relative to students' satisfaction.

Perception of team-based learning using the team-based learning student assessment instrument: an exploratory analysis within pharmacy and biomedical students in the United Kingdom.

PURPOSE: This study aimed to evaluate students' perception of team-based learning (TBL) amongst a cohort who was exposed to this methodology for the first time at an university in the United Kingdom . METHODS: Between November and December 2018, 26 first year Master of Pharmacy and 90 second year B.Sc. Biomedical Science students of School of Life Sciences, University of Sussex, United Kingdom were invited to participate and requested to complete a questionnaire that contained quantitative and qualitative questions. The quantitative component was based on the team-based-learning student assessment instrument (TBL-SAI) instrument. It additionally contained questions about key student characteristics. RESULTS: The response rate was 60% (70/116), 74% (n=52) were females and 26% (n=18) males. The percentage of agreement in the TBL-SAI suggested a favourable response to TBL. The overall mean score for the TBL-SAI was 115.6 (SD 5.6) [maximum score: 140] which was above the threshold of 102, thus suggesting a preference for TBL. Statistically significant differences were not found according to demographics characteristics. Students who predicted a final result of ≥70% strongly agreed that TBL help improve their grades. Some students highlighted issues with working in teams and only 56% of students agreed that they could learn better in a team setting. CONCLUSION: This study shows that students exposed to TBL for the first-time favour several aspects of it. However, more focused strategies including team-building exercises activities and expert facilitation skills could potentially tackle resistance to working in teams.

Engineered signaling centers for the spatially controlled patterning of human pluripotent stem cells.

Signaling centers, localized groups of cells that secrete morphogens, play a key role in early development and organogenesis by orchestrating spatial cell fate patterning. Here we present a microfluidic approach that exposes human pluripotent stem cell (hPSC) colonies to spatiotemporally controlled morphogen gradients generated from artificial signaling centers. In response to a localized source of bone morphogenetic protein 4 (BMP4), hPSC colonies reproducibly break their intrinsic radial symmetry to produce distinct, axially arranged differentiation domains. Counteracting sources of the BMP antagonist NOGGIN enhance this spatial control of cell fate patterning. We also show how morphogen concentration and cell density affect the BMP response and germ layer patterning. These results demonstrate that the intrinsic capacity of stem cells for self-organization can be extrinsically controlled through the use of engineered signaling centers.

Consistency and replicability of a pharmacist-led intervention for asthma patients: Italian Medicines Use Review (I-MUR).

AimThis study aimed to assess the consistency and replicability of these process measures during provision of the Italian Medicines Use Review (I-MUR). BACKGROUND: Medication review is a common intervention provided by community pharmacists in many countries, but with little evidence of consistency and replicability. The I-MUR utilised a standardised question template in two separate large-scale studies. The template facilitated pharmacists in recording medicines and problems reported by patients, the pharmaceutical care issues (PCIs) they found and actions they took to improve medicines use. METHODS: Community pharmacists from four cities and across 15 regions were involved in the two studies. Patients included were adults with asthma. Medicines use, adherence, asthma problems, PCIs and actions taken by pharmacists were compared across studies to assess consistency and replicability of I-MUR.FindingsThe total number of pharmacists and patients completing the studies was 275 and 1711, respectively. No statistically significant differences were found between the studies in the following domains: patients' demographic, patients' perceived problems, adherence, asthma medicines used and healthy living advice provided by pharmacists. The proportion of patients in which pharmacists identified PCIs was similar across both studies. There were differences only in the incidence of non-steroidal anti-inflammatory drug use, the frequency of potential drug-disease interactions and in the types of advice given to patients and GPs. CONCLUSIONS: The use of a standardised template for the I-MUR may have contributed to a degree of consistency in the issues found, which suggests this intervention could have good replicability.

Novel pharmacist-led intervention secures the minimally important difference (MID) in Asthma Control Test (ACT) score: better outcomes for patients and the healthcare provider.

INTRODUCTION: A key priority in asthma management is achieving control. The Asthma Control Test (ACT) is a validated tool showing a numerical indicator which has the potential to provide a target to drive management. A novel pharmacist-led intervention recently evaluated and introduced in the Italian setting with a cluster randomised controlled trial (C-RCT) showed effectiveness and cost-effectiveness. This paper evaluates whether the intervention is successful in securing the minimally important difference (MID) in the ACT score and provides better health outcomes and economic savings. METHODS: Clinical data were sourced from 816 adult patients with asthma participating in the C-RCT. The success of the intervention was measured looking at the proportion of patients reaching MID in the ACT score. Different levels of asthma control were grouped according to international guidelines and graded using the traffic light rating system. Asthma control levels were linked to economic (National Health Service (NHS) costs) and quality-adjusted life years outcomes using published data. RESULTS: The median ACT score was 19 (partially controlled) at baseline, and 20 and 21 (controlled) at 3-month and 6-month-follow up, respectively (p<0.01). The percentage of patients reaching MID at 3 and 6 months was 15.8% (129) and 19.9% (162), respectively. The overall annual NHS cost savings per 1000 patients attached to the shift towards the MID target were equal to €346 012 at 3 months and increased to €425 483 at 6 months. Health utility gains were equal to 35.42 and 45.12 years in full health gained, respectively. DISCUSSION: The pharmacist-led intervention secured the MID in the ACT score and provided better outcomes for both patients and providers.

A single blind, multicenter, randomized controlled trial to evaluate the effectiveness and cost of a novel nutraceutical (LopiGLIK®) lowering cardiovascular disease risk.

CONTEXT: Cardiovascular disease (CVD) costs the economy €210 billion per year in Europe. There is an association between low-density lipoprotein cholesterol (LDL-C) and CVD risk. OBJECTIVE: To evaluate the cost and effectiveness of LopiGLIK® (LOPI) in lowering LDL-C and CVD risk. DESIGN: Single blind multicenter randomized controlled trial; patients were divided into two groups, subjected to centralized randomization. SETTING: Four Italian regions. PARTICIPANTS: Thirty-one physicians enrolled 573 adult patients with mild hypercholesterolemia between January 2016 and January 2018. INTERVENTION: Patients were treated for 16 weeks either with LOPI (intervention) or Armolipid Plus® (AP; control). OUTCOME MEASURES: Primary outcome: percentage of patients who achieved LDL-C <130 mg/dL. Secondary outcomes: reduction of HbA1c, survival analysis and HR linked to 38.67 mg/dL reduction of LDL-C and 1% reduction of HbA1c. Costs were assessed per unit and cure. RESULTS: Three hundred and seventy patients treated with LOPI and 203 treated with AP were randomized and completed the study. At baseline 8.9% (n=18) patients treated with AP and 9.5% (n=35) treated with LOPI had LDL-C levels <130 mg/dL (P=0.815). At the 16-week follow-up, 41.4% (n=84) of patients treated with AP and 67.6% (n=250) with LOPI achieved LDL-C levels <130 mg/dL (P<0.001). LOPI patients were three times more likely to achieve LDL-C levels <130 mg/dL; adjusted OR 2.97 (95% CI; 2.08-4.24; P<0.001), number needed to treat was four (95% CI; 5.60-2.90; P<0.001). Survival analysis demonstrated the superiority of LOPI vs AP relative to 38.67 mg/dL LDL-C reduction (P<0.002); HR was 0.761 (95% CI; 0.62-0.94; P<0.001). Both products reduced the HbA1c without a significant difference between them (P=0.156). Survival analysis and HR (0.91; 95% CI; 0.70-1.18) estimated for 1% HbA1c reduction, showed differences between LOPI and AP, which were not significant (P=0.411; P=0.464). The cost of LOPI was €2.11 (unit), €211 (cure), and AP €3.77 and €377, respectively. CONCLUSION: LOPI appeared more effective and less expensive than AP in lowering LDL-C and CVD risk. TRIAL REGISTRATION: NCT02898805, September 8, 2016.

Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4.

Cancer cells rely on dysregulated gene expression. This establishes specific transcriptional addictions that may be therapeutically exploited. Yet, the mechanisms that are ultimately responsible for these addictions are poorly understood. Here, we investigated the transcriptional dependencies of transformed cells to the transcription factors YAP and TAZ. YAP/TAZ physically engage the general coactivator bromodomain-containing protein 4 (BRD4), dictating the genome-wide association of BRD4 to chromatin. YAP/TAZ flag a large set of enhancers with super-enhancer-like functional properties. YAP/TAZ-bound enhancers mediate the recruitment of BRD4 and RNA polymerase II at YAP/TAZ-regulated promoters, boosting the expression of a host of growth-regulating genes. Treatment with small-molecule inhibitors of BRD4 blunts YAP/TAZ pro-tumorigenic activity in several cell or tissue contexts, causes the regression of pre-established, YAP/TAZ-addicted neoplastic lesions and reverts drug resistance. This work sheds light on essential mediators, mechanisms and genome-wide regulatory elements that are responsible for transcriptional addiction in cancer and lays the groundwork for a rational use of BET inhibitors according to YAP/TAZ biology.

Progress and potential in organoid research.

Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.

A cluster randomised control trial to evaluate the effectiveness and cost-effectiveness of the Italian medicines use review (I-MUR) for asthma patients.

BACKGROUND: The economic burden of asthma, which relates to the degree of control, is €5 billion annually in Italy. Pharmacists could help improve asthma control, reducing this burden. This study aimed to evaluate the effectiveness and cost-effectiveness of Medicines Use Reviews provided by community pharmacists in asthma. METHODS: This cluster randomised, multi-centre, controlled trial in adult patients with asthma was conducted in 15 of the 20 regions of Italy between September 2014 and July 2015. After stratification by region, community pharmacists were randomly allocated to group A (trained in and delivered the intervention at baseline) or B (training and delivery 3 months later), using computerised random number generation in blocks of 10. Each recruited up to five patients, with both groups followed for 9 months. The intervention consisted of a systematic, structured face-to-face consultation with a pharmacist, covering asthma symptoms, medicines used, attitude towards medicines and adherence, recording pharmacist-identified pharmaceutical care issues (PCIs). The primary outcome was asthma control, assessed using the Asthma-Control-Test (ACT) score (ACT ≥ 20 represents good control). Secondary outcomes were: number of active ingredients, adherence, cost-effectiveness compared with usual care. Although blinding was not possible for either pharmacists or patients, assessment of outcomes was conducted by researchers blind to group allocation. RESULTS: Numbers of pharmacists and patients enrolled were 283 (A = 136; B = 147) and 1263 (A = 600; B = 663), numbers completing were 201 (A = 97; B = 104) and 816 (A = 400; B = 416), respectively. Patients were similar in age and gender and 56.13% (458/816) had poor/partial asthma control. Pharmacists identified 1256 PCIs (mean 1.54/patient), mostly need for education, monitoring and potentially ineffective therapy. Median ACT score at baseline differed between groups (A = 19, B = 18; p < 0.01). Odds ratio for improved asthma control was 1.76 (95% CI 1.33-2.33) and number needed to treat 10 (95% CI 6-28). Number of active ingredients reduced by 7.9% post-intervention (p < 0.01). Adherence improved by 35.4% 3 months post-intervention and 40.0% at 6 months (p < 0.01). The probability of the intervention being more cost-effective than usual care was 100% at 9 months. CONCLUSIONS: This community pharmacist-based intervention demonstrated both effectiveness and cost-effectiveness. It has since been implemented as the first community pharmacy cognitive service in Italy. TRIAL REGISTRATION: TRN: ISRCTN72438848 (registered 5th January 2015, retrospectively).

Designer matrices for intestinal stem cell and organoid culture.

Epithelial organoids recapitulate multiple aspects of real organs, making them promising models of organ development, function and disease. However, the full potential of organoids in research and therapy has remained unrealized, owing to the poorly defined animal-derived matrices in which they are grown. Here we used modular synthetic hydrogel networks to define the key extracellular matrix (ECM) parameters that govern intestinal stem cell (ISC) expansion and organoid formation, and show that separate stages of the process require different mechanical environments and ECM components. In particular, fibronectin-based adhesion was sufficient for ISC survival and proliferation. High matrix stiffness significantly enhanced ISC expansion through a yes-associated protein 1 (YAP)-dependent mechanism. ISC differentiation and organoid formation, on the other hand, required a soft matrix and laminin-based adhesion. We used these insights to build a fully defined culture system for the expansion of mouse and human ISCs. We also produced mechanically dynamic matrices that were initially optimal for ISC expansion and subsequently permissive to differentiation and intestinal organoid formation, thus creating well-defined alternatives to animal-derived matrices for the culture of mouse and human stem-cell-derived organoids. Our approach overcomes multiple limitations of current organoid cultures and greatly expands their applicability in basic and clinical research. The principles presented here can be extended to identify designer matrices that are optimal for long-term culture of other types of stem cells and organoids.