Assessment of the Effectiveness and Cost-Effectiveness of Tailored Web- and Text-Based Smoking Cessation Support in Primary Care (iQuit in Practice II): Protocol for a Randomized Controlled Trial.

BACKGROUND: The prevalence of smoking is declining; however, it continues to be a major public health burden. In England, primary care is the health setting that provides smoking cessation support to most smokers. However, this setting has one of the lowest success rates. The iQuit in practice intervention (iQuit) is a tailored web-based and text message intervention developed for use in primary care consultations as an adjunct to routine smoking cessation support with the aim of increasing success rates. iQuit has demonstrated feasibility, acceptability, and potential effectiveness. OBJECTIVE: This definitive trial aims to determine the effectiveness and cost-effectiveness of iQuit when used as an adjunct to the usual support provided to patients who wish to quit smoking, compared with usual care alone. METHODS: The iQuit in Practice II trial is a two-arm, parallel-group, randomized controlled trial (RCT) with a 1:1 individual allocation comparing usual care (ie, pharmacotherapy combined with multisession behavioral support)-the control-with usual care plus iQuit-the intervention. Participants were recruited through primary care clinics and talked to a smoking cessation advisor. Participants were randomized during the initial consultation, and those allocated to the intervention group received a tailored advice report and 90 days of text messaging in addition to the standard support provided to all patients. RESULTS: The primary outcome is self-reported prolonged abstinence biochemically verified using saliva cotinine at 6 months after the quit date. A sample size of 1700 participants, with 850 per arm, would yield 90% power to detect a 4.3% difference in validated quit rates between the groups at the two-sided 5% level of significance. The Cambridge East Research Ethics Committee approved the study in February 2016, and funding for the study was granted from May 2016. In total, 1671 participants were recruited between August 2016 and July 2019. Follow-up for all participants was completed in January 2020. Data analysis will begin in the summer of 2020. CONCLUSIONS: iQuit in Practice II is a definitive, pragmatic RCT assessing whether a digital intervention can augment the impact of routine smoking cessation support in primary care. Previous research has found good acceptability and feasibility for delivering iQuit among smoking cessation advisors working in primary care. If demonstrated to be cost-effective, iQuit could be delivered across primary care and other settings, such as community pharmacies. The potential benefit would likely be highest where less behavioral support is delivered. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 44559004; http://www.isrctn.com /ISRCTN44559004. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17160

Study protocol for iQuit in Practice: a randomised controlled trial to assess the feasibility, acceptability and effectiveness of tailored web- and text-based facilitation of smoking cessation in primary care.

BACKGROUND: Primary care is an important setting for smoking cessation interventions. There is evidence for the effectiveness of tailored interventions for smoking cessation, and text messaging interventions for smoking cessation show promise. The intervention to be evaluated in this trial consists of two components: (1) a web-based program designed to be used by a practice nurse or other smoking cessation advisor (SCA); the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker; and (2) a three-month programme of automated tailored text messages sent to the smoker's mobile phone. The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone. METHODS/DESIGN: The design is a two parallel group randomised controlled trial (RCT). 600 smokers who want to quit will be recruited in up to 30 general practices in the East of England. During a consultation with an SCA, they will be individually randomised by computer program to usual care (Control) or to usual care plus the iQuit system (Intervention). At the four-week follow-up appointment, the SCA will record smoking status and measure carbon monoxide level. There will be two further follow-ups, at eight weeks and six months from randomisation date, by postal questionnaire sent from and returned to the study centre or by telephone interview conducted by a research interviewer. The primary outcome will be self-reported abstinence for at least two weeks at eight weeks. A sample size of 300 per group would give 80% power to detect an increase in quit rate from 20% to 30% (alpha = 0.05, 2-sided test). The main analyses of quit rates will be conducted on an intention-to-treat basis, making the usual assumption that participants lost to follow up are smoking. DISCUSSION: This trial will focus on acceptability, feasibility and short-term effectiveness. The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness. TRIAL REGISTRATION: ISRCTN56702353.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Randomized controlled trial to assess the short-term effectiveness of tailored web- and text-based facilitation of smoking cessation in primary care (iQuit in practice).

AIMS: To estimate the short-term effectiveness, feasibility and acceptability of a smoking cessation intervention (the iQuit system) that consists of tailored printed and Short Message Service (SMS) text message self-help delivered as an adjunct to cessation support in primary care to inform the design of a definitive trial. DESIGN: A stratified two parallel-group randomized controlled trial comparing usual care (control) with usual care plus the iQuit system (intervention), delivered by primary care nurses/healthcare assistants who were blinded to the allocation sequence. SETTING: Thirty-two general practice (GP) surgeries in England, UK. PARTICIPANTS: A total of 602 smokers initiating smoking cessation support from their local GP surgery were randomized (control n = 303, intervention n = 299). MEASUREMENTS: Primary outcome was self-reported 2-week point prevalence abstinence at 8 weeks follow-up. Secondary smoking outcomes and feasibility and acceptability measures were collected at 4 weeks after quit date, 8 weeks and 6 months follow-up. FINDINGS: There were no significant between-group differences in the primary outcome [control 40.3%, iQuit 45.2%; odds ratio (OR) = 1.22, 95% confidence interval (CI) = 0.88-1.69] or in secondary short-term smoking outcomes. Six-month prolonged abstinence was significantly higher in the iQuit arm (control 8.9%, iQuit 15.1%; OR = 1.81, 95% CI = 1.09-3.01). iQuit support took on average 7.7 minutes (standard deviation = 4.0) to deliver and 18.9% (95% CI = 14.8-23.7%) of intervention participants discontinued the text message support during the programme. CONCLUSIONS: Tailored printed and text message self-help delivered alongside routine smoking cessation support in primary care does not significantly increase short-term abstinence, but may increase long-term abstinence and demonstrated feasibility and acceptability compared with routine cessation support alone

Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6-9) and machaeridiols A-C (10-12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6-8 and 10-12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with \u3e32- and \u3e8-fold reduction of MIC\u27s, compared to 12, against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5-8 µg/mL for two strains of Acinetobacter baumannii, 2-16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC \u3e 64 µg/mL) against the two isolates of Klebsiella pneumoniae

Path to Success: Development of the Pharmacist Through the Continuum of Pharmacy School and Beyond

Objective: To explore the processes and opportunities provided in the co-curriculum of the Wegmans School of Pharmacy (WSoP) that contribute to the development of successful pharmacy graduates. Methods: Pharmacy career preparation begins at orientation with workshops on emotional intelligence, leadership, and the APhA Career Pathway Evaluation Program. During the P1 through P4 years, the optional Student Development Workshop Series (SDW) offers seminars for students on a variety of topics including time management, exam taking strategies/anxiety management, learning styles, personal “brand” creation, CV/portfolio development, and interview soft skills. All students may participate in the annual WSoP Career Day, which offers networking and career opportunities, including post-graduate training options. During the P4 year, there is opportunity for a structured Residency/Fellowship Preparation Program (RPP). Additionally, local pharmacy residents/fellows participate in a Residency Teaching/Learning Curriculum Program (TLC) to develop academic teaching and precepting skills. Results: The SDW program has been successful and well attended with greater than 90% of students finding the topics relevant to their post-graduate success. After the RPP, ASHP residency match results in the 2016 class yielded an improvement from previous years, with 76 % of applied students and 94% of ranked students matching programs in Phase 1. Of the TLC participants, 90% documented an improvement in multiple types of teaching skills. Implications: Based on data and student/faculty input, career development is reassessed and improved continuously at WSoP. In the near future, a method for tracking graduates will be designed to further monitor the impact of programs on student success

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Puberty classifications in beef heifers are moderately to highly heritable and associated with candidate genes related to cyclicity and timing of puberty

Introduction: Pubertal attainment is critical to reproductive longevity in heifers. Previously, four heifer pubertal classifications were identified according to attainment of blood plasma progesterone concentrations > 1 ng/ml: 1) Early; 2) Typical; 3) Start-Stop; and 4) Non-Cycling. Early and Typical heifers initiated and maintained cyclicity, Start-Stop started and then stopped cyclicity and Non-Cycling never initiated cyclicity. Start-Stop heifers segregated into Start-Stop-Discontinuous (SSD) or Start-Stop-Start (SSS), with SSD having similar phenotypes to Non-Cycling and SSS to Typical heifers. We hypothesized that these pubertal classifications are heritable, and loci associated with pubertal classifications could be identified by genome wide association studies (GWAS).Methods: Heifers (n = 532; 2017 – 2022) genotyped on the Illumina Bovine SNP50 v2 or GGP Bovine 100K SNP panels were used for variant component estimation and GWAS. Heritability was estimated using a univariate Bayesian animal model.Results: When considering pubertal classifications: Early, Typical, SSS, SSD, and Non-Cycling, pubertal class was moderately heritable (0.38 ± 0.08). However, when heifers who initiated and maintained cyclicity were compared to those that did not cycle (Early+Typical vs. SSD+Non-Cycling) heritability was greater (0.59 ± 0.19). A GWAS did not identify single nucleotide polymorphisms (SNPs) significantly associated with pubertal classifications, indicating puberty is a polygenic trait. A candidate gene approach was used, which fitted SNPs within or nearby a set of 71 candidate genes previously associated with puberty, PCOS, cyclicity, regulation of hormone secretion, signal transduction, and methylation. Eight genes/regions were associated with pubertal classifications, and twenty-two genes/regions were associated with whether puberty was attained during the trial. Additionally, whole genome sequencing (WGS) data on 33 heifers were aligned to the reference genome (ARS-UCD1.2) to identify variants in FSHR, a gene critical to pubertal attainment. Fisher’s exact test determined if FSHR SNPs segregated by pubertal classification. Two FSHR SNPs that were not on the bovine SNP panel were selected for additional genotyping and analysis, and one was associated with pubertal classifications and whether they cycled during the trial.Discussion: In summary, these pubertal classifications are moderately to highly heritable and polygenic. Consequently, genomic tools to inform selection/management of replacement heifers would be useful if informed by SNPs associated with cyclicity and early pubertal attainment

Introduction

info:eu-repo/semantics/publishe

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>Experimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4⁺ T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s). Despite some sporadic reports, however, models of DC-driven EAE have not been widely adopted. We sought to test the feasibility of this approach and whether activation of the DC by toll-like receptor (TLR)-4 ligation was a sufficient stimulus to drive EAE.</p> <p>Findings</p> <p>Host mice were seeded with myelin basic protein (MBP)-reactive CD4+ T cells and then were injected with DC that could present the relevant MBP peptide which had been exposed to lipopolysaccharide as a TLR-4 agonist. We found that this approach induced robust clinical signs of EAE.</p> <p>Conclusions</p> <p>DC are sufficient as APC to effectively drive the differentiation of naïve myelin-responsive T cells into autoaggressive effector T cells. TLR-4-stimulation can activate the DC sufficiently to deliver the signals required to drive the pathogenic function of the T cell. These models will allow the dissection of the molecular requirements of the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the central nervous system.</p

Insights into the Spectrum of Activity and Mechanism of Action of MGB-BP-3

MGB-BP-3 is a potential first-in-class antibiotic, a Strathclyde Minor Groove Binder (S-MGB), that has successfully completed Phase IIa clinical trials for the treatment of Clostridioides difficile associated disease. Its precise mechanism of action and the origin of limited activity against Gram-negative pathogens are relatively unknown. Herein, treatment with MGB-BP-3 alone significantly inhibited the bacterial growth of the Gram-positive, but not Gram-negative, bacteria as expected. Synergy assays revealed that inefficient intracellular accumulation, through both permeation and efflux, is the likely reason for lack of Gram-negative activity. MGB-BP-3 has strong interactions with its intracellular target, DNA, in both Gram-negative and Gram-positive bacteria, revealed through ultraviolet–visible (UV–vis) thermal melting and fluorescence intercalator displacement assays. MGB-BP-3 was confirmed to bind to dsDNA as a dimer using nano-electrospray ionization mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Type II bacterial topoisomerase inhibition assays revealed that MGB-BP-3 was able to interfere with the supercoiling action of gyrase and the relaxation and decatenation actions of topoisomerase IV of both Staphylococcus aureus and Escherichia coli. However, no evidence of stabilization of the cleavage complexes was observed, such as for fluoroquinolones, confirmed by a lack of induction of DSBs and the SOS response in E. coli reporter strains. These results highlight additional mechanisms of action of MGB-BP-3, including interference of the action of type II bacterial topoisomerases. While MGB-BP-3′s lack of Gram-negative activity was confirmed, and an understanding of this presented, the recognition that MGB-BP-3 can target DNA of Gram-negative organisms will enable further iterations of design to achieve a Gram-negative active S-MGB