Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology.

OBJECTIVES: Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD. METHODS: IgG binding to a high-density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca-controls without autoimmunity (n=75) and autoimmune-feature controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for binding abundance and controlled false discovery rate in group comparisons. For predictive modelling, we used logistic regression, model selection methods and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity. RESULTS: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) bound more in SSA- SjD than sicca-controls (p=0.004) and combined controls (sicca-controls and autoimmune-feature controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 and DTD2 were bound more in FS-positive than FS-negative participants (p=0.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (area under the curve (AUC) 74%) and between FS-positive versus FS-negative (AUC 72%). CONCLUSION: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS positivity.

The Impact of Periodontal Inflammation on the Severity of Coronary Atherosclerosis.

Introduction Through plausible biological mechanisms, periodontitis causes systemic inflammatory burden and response, thus resulting in damage far beyond the oral cavity. Studies have demonstrated periodontitis to be a significant risk factor for coronary heart disease (CHD) and stroke. The larger the quantum of periodontal inflamed tissue, the greater the chances of periodontitis eliciting bacteremia and systemic inflammatory responses. Studies have reported that periodontitis and other common oral infections play an important role in the development of atherosclerosis. Therefore, the quantity of inflamed periodontal tissue assumes significance in determining the severity of atherosclerosis. Hence, this study investigates the impact of periodontal inflamed surface area (PISA) on the severity of coronary atherosclerosis. Materials and methods In this cross-sectional study, a total of 160 patients who presented at the department of periodontics of The British University in Egypt (BUE) from 1 January 2023 to 30 September 2023 were enrolled. Patients were only enrolled if they had undergone coronary angiography within the last six months, were less than 60 years of age, shared their previous medical history and coronary angiographic report, and gave informed written consent. Data on classic coronary risk factors and periodontal inflammatory status and angiographic findings were recorded and subjected to appropriate statistical analysis. Results The results revealed that the periodontal inflamed surface area (p = 0.002) apart from age (p < 0.047) and low-density lipoprotein cholesterol (LDL-C) (p < 0.001) is a significant independent predictor of the severity of coronary atherosclerosis. Conclusions The periodontal inflamed surface area is an independent predictor of the severity of coronary atherosclerosis.

Effects of Preoperative COVID-19 Status on Emergent or Urgent Colectomy Outcomes.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID+ (n = 242) and COVID- cohorts (n = 11,049). Several clinical variables were compared. RESULTS: Before filtering for urgent/emergent operations, a large percentage of COVID+ patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001. CONCLUSIONS: Urgent or emergent colectomy patients who were COVID-19+ preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.

Pathogenomes and virulence profiles of representative big six non-O157 serogroup Shiga toxin-producing Escherichia coli.

Shiga toxin (Stx)-producing Escherichia coli (STEC) of non-O157:H7 serotypes are responsible for global and widespread human food-borne disease. Among these serogroups, O26, O45, O103, O111, O121, and O145 account for the majority of clinical infections and are colloquially referred to as the "Big Six." The "Big Six" strain panel we sequenced and analyzed in this study are reference type cultures comprised of six strains representing each of the non-O157 STEC serogroups curated and distributed by the American Type Culture Collection (ATCC) as a resource to the research community under panel number ATCC MP-9. The application of long- and short-read hybrid sequencing yielded closed chromosomes and a total of 14 plasmids of diverse functions. Through high-resolution comparative phylogenomics, we cataloged the shared and strain-specific virulence and resistance gene content and established the close relationship of serogroup O26 and O103 strains featuring flagellar H-type 11. Virulence phenotyping revealed statistically significant differences in the Stx-production capabilities that we found to be correlated to the strain's individual stx-status. Among the carried Stx1a, Stx2a, and Stx2d phages, the Stx2a phage is by far the most responsive upon RecA-mediated phage mobilization, and in consequence, stx2a + isolates produced the highest-level of toxin in this panel. The availability of high-quality closed genomes for this "Big Six" reference set, including carried plasmids, along with the recorded genomic virulence profiles and Stx-production phenotypes will provide a valuable foundation to further explore the plasticity in evolutionary trajectories in these emerging non-O157 STEC lineages, which are major culprits of human food-borne disease.

A Novel Variant of the LMAN1 Gene in Combined Factor V and Factor VIII Deficiency in a Saudi Female Child: A Case Report.

Combined factor V and factor VIII deficiency (F5F8D) is an exceedingly rare autosomal recessive disease that causes concomitantly low levels of factor V and factor VIII, leading to mild to moderate bleeding tendencies. Within this disorder, mutations manifest in the lectin mannose-binding protein (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) genes. This report presents a case of a five-year-old Saudi female child who was referred from an otolaryngology clinic, with an incidental finding of prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) detected during routine preoperative investigations for tonsillectomy, prompting further investigations. There was no prior history of bleeding symptoms in the patient. She was discovered to have low assays of factor V and factor VIII on subsequent investigations. Whole exome sequencing revealed the novel homozygous mutation c.604C>T in the LMAN1 gene, validating the diagnosis of F5F8D.

Disability and pain after anterior cervical decompression and fusion: A group-based trajectory analysis.

OBJECTIVES: This study aimed to identify the clusters of patients with different developmental trajectories of pain and disability after anterior cervical decompression and fusion (ACDF). METHODS: Group-based trajectory analysis among 318 patients undergoing the ACDF. RESULTS: Three developmental trajectories of disability were identified: "Steadily good functioning," "Improved functioning," and "Steadily poor functioning." Three developmental trajectories of neck pain were identified: "Worsened pain," "Pain relief," and "Steadily severe pain." Two developmental trajectories of arm pain were identified: "Decreased arm pain" and "Severe arm pain with only short-term relief." No associations were found between sex, preoperative pain duration, or body weight and probability to be classified into a particular disability trajectory group. Female sex (relative risk ratio (RRR) 1.78) and longer history of preoperative pain (RRR 2.31-2.68) increased the probability to be classified into a group with steadily severe neck pain. Longer history of preoperative pain increased the probability to be classified into group with severe arm pain with only short-term pain relief (RRR 2.68). CONCLUSION: After the ACDF, dissimilar developmental trajectories of pain and disability were identified between the patient clusters. While sex, preoperative pain duration, and body weight were not associated with differences in improvement in disability level, female sex and longer duration of preoperative pain were correlated with more severe neck and arm pain after surgery.

Multifaceted pharmacist-led interventions in secondary care settings between countries of various income levels: a scoping review protocol.

INTRODUCTION: Clinical pharmacy services often involve multifaceted pharmacist-led interventions. However, current pharmacy practice models vary across different countries. Despite the documented benefits of clinical pharmacy services, the characteristics of pharmacist-led interventions in different countries have not yet been adequately explored and described. Therefore, this protocol outlines the methodology for a proposed scoping review aiming to investigate various types of multifaceted pharmacist-led interventions and the outcomes used to evaluate their effectiveness within secondary care settings. Additionally, the scoping review will map the current evidence surrounding the characteristics of interventions and outcomes reported across various countries of socioeconomic status. METHODS AND ANALYSIS: The scoping review will be conducted according to the JBI Methodology for Scoping Reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews. We will systematically search the following electronic databases: MEDLINE (Ovid), CINAHL (EbscoHost), Embase (embase.com), Scopus (scopus.com), Cochrane Library (cochranelibrary.com) and APA PsycInfo (Ovid). Additionally, the reference lists of identified reviews and included full texts will be searched for relevant papers. Grey literature sources, such as International Pharmaceutical Abstracts and the International Pharmaceutical Federation (FIP) website, will be searched. We will include primary studies published in the English language from January 2013 to December 2023, involving secondary care multifaceted pharmacist-led interventions. Two independent reviewers will screen studies against eligibility criteria and use a piloted data extraction form to extract relevant information. We will extract relevant data, complete a tabular summary from each included publication and analyse it. ETHICS AND DISSEMINATION: Ethical approval is not required as we will be using data from publicly available literature sources. Findings will be disseminated in publications and presentations with relevant stakeholders. We aim to map available evidence across the breadth of studies that have reported multifaceted pharmacist-led interventions and their outcomes.

Pathogenomes of Shiga Toxin Positive and Negative Escherichia coli O157:H7 Strains TT12A and TT12B: Comprehensive Phylogenomic Analysis Using Closed Genomes.

Shiga toxin-producing Escherichia coli are zoonotic pathogens that cause food-borne human disease. Among these, the O157:H7 serotype has evolved from an enteropathogenic O55:H7 ancestor through the displacement of the somatic gene cluster and recurrent toxigenic conversion by Shiga toxin-converting bacteriophages. However, atypical strains that lack the Shiga toxin, the characteristic virulence hallmark, are circulating in this lineage. For this study, we analyzed the pathogenome and virulence inventories of the stx+ strain, TT12A, isolated from a patient with hemorrhagic colitis, and its respective co-isolated stx- strain, TT12B. Sequencing the genomes to closure proved critical to the cataloguing of subtle strain differentiating sequence and structural polymorphisms at a high-level of phylogenetic accuracy and resolution. Phylogenomic profiling revealed SNP and MLST profiles similar to the near clonal outbreak isolates. Their prophage inventories, however, were notably different. The attenuated atypical non-shigatoxigenic status of TT12B is explained by the absence of both the ΦStx1a- and ΦStx2a-prophages carried by TT12A, and we also recorded further alterations in the non-Stx prophage complement. Phenotypic characterization indicated that culture growth was directly impacted by the strains' distinct lytic phage complement. Altogether, our phylogenomic and phenotypic analyses show that these intimately related isogenic strains are on divergent Stx(+/stx-) evolutionary paths.

Sensitive "release-on-demand" fluorescent genosensors for probing DNA damage induced by commonly used cardiovascular drugs: Comparative study.

Cardiovascular drugs (CVDs) are agents working on the heart and the vascular system to treat many cardiovascular disorders. Such disorders represent the leading cause for morbidity and mortality worldwide. The treatment regimen includes different administered drugs on chronic basis. The cumulative drugs in human body coincides with exposure to electromagnetic radiations from different sources leading to drug-radiation interaction that may lead to drug photosensitization. Such photosensitization may lead to mutagenesis, cancer, and cell death due to molecular damage to DNA. This work involves the application of two bioluminescent genosensors; Terbium chloride and EvaGreen are utilized to investigate potential DNA damage caused by frequently used CVDs following UVA irradiation. A variety of CVDs are investigated. Ten drugs; Amiloride, Atorvastatin, Captopril, Enalapril, Felodipine, Hydrochlorothiazide, Indapamide, Losartan, Triamterene and Valsartan are studied. The study's findings showed that such drugs induced DNA damage following UVA irradiation. The induced DNA damage altered the fluorescence of terbium chloride and EvaGreen genosensors, proportionally. The results are confirmed by viscosity measurements reflecting the possible intercalation of CVDs with DNA. Also, the work is applied on calf thymus DNA to mimic the actual biological variability. The demonstrated bioluminescent genosensors provide automatic, simple and low-cost methods for assessing DNA-drug interactions.

Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study.

Schizophrenia is a chronic mental illness with a poor quality of life (QoL). The main aim of this study was to measure the QoL and factors that affect the QoL of patients with schizophrenia placed in a social welfare institution. This cross-sectional study included 287 patients with schizophrenia who were treated in a long-stay social care institution in which QoL was assessed using five different instruments: the World Health Organization Quality of Life scale, the EuroQoL Five-Dimension-Five-Level scale (including the visual analog scale), the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form, and the Brief Psychiatric Rating Scale. To determine the impact of patients' characteristics on score values, multiple linear regression using backward elimination was employed. Due to non-normality in the distribution of the dependent variables, a Box-Cox power transformation was applied to each dependent variable prior to conducting multiple linear regression analysis. Results revealed that patients with schizophrenia have lower QoL. Our study revealed that age, level of education, type of accommodation, type of pavilion, age of onset of the disease, number of prescribed antipsychotics, number of psychiatric comorbidities, duration of therapy, and the number of daily doses of antipsychotics are dominant contributors to the QoL in patients with schizophrenia who were treated in social welfare institution.

Repurposing Phytochemicals against Breast Cancer (MCF-7) using Classical Structure-Based Drug Design.

BACKGROUND: The significant public health effect of breast cancer is demonstrated by its high global prevalence and the potential for severe health consequences. The suppression of the proliferative effects facilitated by the estrogen receptor alpha (ERα) in the MCF-7 cell line is significant for breast cancer therapy. OBJECTIVE: The current work involves in-silico techniques for identifying potential inhibitors of ERα. METHODS: The method combines QSAR models based on machine learning with molecular docking to identify potential binders for the ERα. Further, molecular dynamics simulation studied the stability of the complexes, and ADMET analysis validated the compound's properties. RESULT: Two compounds (162412 and 443440) showed significant binding affinities with ERα, with binding energies comparable to the established binder RL4. The ADMET qualities showed advantageous characteristics resembling pharmaceutical drugs. The stable binding of these ligands in the active region of ERα during dynamic conditions was confirmed by molecular dynamics simulations. RMSD plots and conformational stability supported the ligands' persistent occupancy in the protein's binding site. After simulation, two hydrogen bonds were found within the protein-ligand complexes of 162412 and 443440, with binding free energy values of -27.32 kcal/mol and -25.00 kcal/mol. CONCLUSION: The study suggests that compounds 162412 and 443440 could be useful for developing innovative anti-ERα medicines. However, more research is needed to prove the compounds' breast cancer treatment efficacy. This will help develop new treatments for ERα-associated breast cancer.

The relationship between cleft palate repair technique and audiological outcomes: A retrospective cohort study.

Objective: Otitis media with effusion is common in children with cleft palates. This study aimed to investigate the link between palatal closure techniques and audiological outcomes. Methods: In this retrospective-prospective cohort study, we examined the relationship between palate repair techniques and hearing outcomes in children with cleft palates. From 2017 to 2022, 190 ears of 95 cleft patients were studied at the Cleft Lip and Palate Department of Shiraz University of Medical Sciences. Variables assessed included the surgical technique, cleft severity, auditory brainstem response (ABR) threshold, and tympanometry configuration. Results: The mean ABR improved from a prepalatoplasty value of 39.51(11.62) decibels (dB) to a postpalatoplasty mean of 26.61(11.60) dB (Cohen's d: 1.12 [95% CI; 0.90-1.34]). Initially, 87.9% of the studied ears exhibited abnormal tympanometry, but this significantly decreased to 47% postsurgery (risk ratio: 4.43 [95% CI; 1.20-16.43]). When compared with Sommerlad intravelar veloplasty, the Nadjmi modified Furlow palatoplasty was associated with a notably lower mean ABR (ß: -6.58 [95% CI: -10.43 to -2.73], p-value = .001) and a reduced frequency of abnormal tympanometry (odds ratio [OR]: -1.10; 95% CI: -1.85 to -0.36, p-value = .004). Factors like prepalatoplasty ABR, cleft palate severity, gender, and syndromic did not confound these findings. Conclusions: Although the Nadjmi modified Furlow palatoplasty showed better results, our findings indicate a significant improvement in ABR and tympanometry outcomes for both techniques. Future randomized controlled trials are suggested to confirm the influence of palatal closure techniques on audiological outcomes. Level of Evidence: 3b.

RETRACTED: Alhakamy et al. Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats. Biomolecules 2020, 10, 1006.

The journal retracts the article, "Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats" [...].

Biventricular catheterization combined with pressure-volume loop monitoring provides insight into the dynamic effects of left ventricular assist devices ramp on right ventricular function.

Ramp studies are utilized for speed optimization of continuous flow left ventricular assist devices (CF-LVADs). We here report the utility of combined left and right heart catheterization during a ramp study to ensure a comprehensive understanding of the hemodynamic implications on both ventricles. Pressure-volume loop (PV loop) monitoring uncovered compromised systolic and mildly compromised right ventricular function with increasing LVAD speeds, despite improvement in left ventricular unloading. These findings informed patient management and highlight the potential utility of PV loop monitoring as an adjunct to left and right heart catheterization during ramp studies of next-generation LVADs.

Mechanisms of endometrial aging: lessons from natural conceptions and assisted reproductive technology cycles.

Until recently, the study of age-related decline in fertility has focused primarily on the ovary; depletion of the finite pool of oocytes and increases in meiotic errors leading to oocyte aneuploidy are well-established mechanisms by which fertility declines with advancing age. Comparatively little is known about the impact of age on endometrial function. The endometrium is a complex tissue comprised of many cell types, including epithelial, stromal, vascular, immune and stem cells. The capacity of this tissue for rapid, cyclic regeneration is unique to this tissue, undergoing repeated cycles of growth and shedding (in the absence of an embryo) in response to ovarian hormones. Furthermore, the endometrium has been shown to be capable of supporting pregnancies beyond the established boundaries of the reproductive lifespan. Despite its longevity, molecular studies have established age-related changes in individual cell populations within the endometrium. Human clinical studies have attempted to isolate the effect of aging on the endometrium by analyzing pregnancies conceived with euploid, high quality embryos. In this review, we explore the existing literature on endometrial aging and its impact on pregnancy outcomes. We begin with an overview of the principles of endometrial physiology and function. We then explore the mechanisms behind endometrial aging in its individual cellular compartments. Finally, we highlight lessons about endometrial aging gleaned from rodent and human clinical studies and propose opportunities for future study to better understand the contribution of the endometrium to age-related decline in fertility.

Exploring the implementation of a novel community pharmacist-led support service for people living with severe and persistent mental illness.

BACKGROUND: Community pharmacists are well-placed to promote and provide mental health medication management services. However, literature evaluating the impact of pharmacy services in supporting people living with severe and persistent mental illness (SPMI) is currently limited. An individualised, goal-oriented pharmacist-led support service that focused on improving the physical and mental health of consumers living with SPMI, namely the PharMIbridge intervention, was provided to consumer participants as part of the PharMIbridge Randomised Controlled Trial (RCT). OBJECTIVE(S): To explore the experiences of the participants who delivered and supported the implementation of the PharMIbridge intervention and propose ideas and supports needed for broader implementation and sustainability of pharmacist-led support services for people living with SPMI. METHODS: Interviews and focus group discussions were undertaken with PharMIbridge pharmacists and mentors, respectively. Audio-recordings were de-identified and transcribed verbatim. Data analysis was conducted using an iterative, inductive approach. The key themes identified were furthered divided into subthemes. Subthemes were then mapped to the EPIS (Exploration, Preparation, Implementation and Sustainment) framework. RESULTS: Data were collected from one focus group involving six RCT mentors and 16 semi-structured interviews with community pharmacists. Five overarching themes emerged: "Training needs", "Pharmacist integration within the healthcare system", "Environmental factors", "Attitudes and behaviour" and "Pharmacy operations". Twelve subthemes were mapped to EPIS phases "Preparation", "Implementation" and "Sustainment" and EPIS constructs "Outer" context, "Inner" context and "Bridging" factors. CONCLUSION: Adequate remuneration and supports to encourage healthcare professional collaboration are necessary to establish and sustain functioning, integrated pharmacy mental health services. A shift in pharmacy business and workflow models is necessary to support community pharmacies to implement mental health services. In addition, there is a need to promote psychological support services to ensure that pharmacists are well supported while delivering pharmacy mental health services.

Multilevel Modeling Analysis of Odontogenic Risk Factors and Nasal Septum Deviation Associated with Maxillary Sinus Mucosal Thickening: A Cone-Beam Computed Tomography Study.

(1) Background: In this study, the impact of odontogenic risk factors with nasal septum deviation on maxillary sinus mucosal thickening was assessed using Cone-beam computed tomography CBCT. (2) Methods: A total of 328 maxillary sinus regions from 164 patients (85 males and 79 females) were examined. Images were interpreted by dental specialists and Otolaryngologists. Coronal and sagittal sections were examined to assess the proximity of the root tips of posterior maxillary teeth (RPMT) to the maxillary sinus. The periodontal bone loss for all maxillary posterior teeth was also assessed. Consequently, maxillary sinus mucosal thickening (MT) was further classified into three gradings. Multilevel modeling regression analysis was used due to the hierarchical structuring of the data. Four models were developed, a null model with no factors, a model with tooth-level factors (RPMT, PBL, tooth condition, and root length), a model with patient-level factors (gender and nasal septum deviation), and a model with combined patient- and tooth-level factors. Regression estimates (AOR) and 95% confidence intervals (CIs) of individual and tooth factors were calculated. (3) Results: Multilevel regression analysis showed that RPMT was significantly associated with MT of maxillary sinus (p < 0.001), where patients who had RPMT > 0 had higher odds of MT of maxillary sinus. Tooth condition was also found to be significantly associated with MT of maxillary sinus, where teeth with failed RCT (p < 0.001) and teeth with restorations (p < 0.008) had higher odds of MT of maxillary sinus (AOR = 2.87, 95%CI 1.65, 4.42, AOR = 1.64, 95%CI 1.14, 2.36, respectively). (4) Conclusions: In order to plan preoperative treatment for maxillary posterior teeth, it is important to assess the anatomical relationship between the sinus floor and the root tips of the maxillary posterior teeth. Additionally, we establish a better understanding of the clinician before surgical intervention is conducted.

Combining user-centered design and behavioral theory to enhance health technologies: A personas-based approach for a primary-care based multifactorial falls risk assessment tool.

INTRODUCTION: Multifactorial falls risk assessment tools (FRATs) can be an effective falls prevention method for older adults, but are often underutilized by health care professionals (HCPs). This study aims to enhance the use and implementation of multifactorial FRATs by combining behavioral theory with the user-centered design (UCD) method of personas construction. Specifically, the study aimed to (1) construct personas that are based on external (i.e., needs, preferences) and intrinsic user characteristics (i.e., behavioral determinants); and (2) use these insights to inform requirements for optimizing an existing Dutch multifactorial FRAT (i.e., the 'Valanalyse'). METHODS: Survey data from HCPs (n = 31) was used to construct personas of the 'Valanalyse.' To examine differences between clusters on 68 clustering variables, a multivariate cluster analysis technique with non-parametric analyses and computational methods was used. The aggregated external and intrinsic user characteristics of personas were used to inform key design and implementation requirements for the 'Valanalyse,' respectively, whereby intrinsic user characteristics were matched with appropriate behavior change techniques to guide implementation. RESULTS: Significant differences between clusters were observed in 20 clustering variables (e.g., behavioral beliefs, situations for use). These variables were used to construct six personas representing users of each cluster. Together, the six personas helped operationalize four key design requirements (e.g., guide treatment-related decision making) and 14 implementation strategies (e.g., planning coping responses) for optimizing the 'Valanalyse' in Dutch geriatric, primary care settings. CONCLUSION: The findings suggest that theory- and evidence-based personas that encompass both external and intrinsic user characteristics are a useful method for understanding how the use and implementation of multifactorial FRATs can be optimized with and for HCPs, providing important implications for developers and eHealth interventions with regards to encouraging technology adoption.

Community pharmacists' views and experiences of delivering in-pharmacy medication reviews for people living with severe and persistent mental illness: a qualitative study.

BACKGROUND: People living with severe and persistent mental illness (SPMI) often take multiple medications and are at risk of experiencing medication related problems. Medication review services have the potential to reduce inappropriate use of psychotropic medications and improve adherence. However, there is limited research regarding pharmacists' perspectives when providing such services. AIM: To explore community pharmacists' views and experiences of providing an in-pharmacy medication review (MedsCheck) for people living with SPMI. METHOD: Semi-structured interviews were conducted between November 2021 and May 2022 with community pharmacists participating in the comparator group of the PharMIbridge Randomised Controlled Trial (RCT), which aimed to improve medication adherence and manage physical health concerns for people living with SPMI. Interviews were recorded, transcribed, and analysed using inductive thematic analysis. RESULTS: Fifteen semi-structured interviews were conducted with community pharmacists including pharmacy owners, managers and employee pharmacists. Most pharmacist participants who were interviewed (n = 10) were aged under 39 and more than half (n = 8) had 10 or more years of pharmacy experience. Five key themes were identified: 1) Pharmacists' roles in the management of SPMI in community pharmacy; 2) Mental health education and training; 3) Pharmacy resources; 4) Challenges with interprofessional collaboration and 5) Impact on professional relationships and consumer outcomes. CONCLUSION: Pharmacists are motivated to support people living with SPMI. Mental health training, as well as arrangements regarding pharmacy workflow and appropriate remuneration are needed to enable pharmacists to better support people living with SPMI. Referral pathways should be directly accessible by community pharmacists to assist interprofessional collaboration.