Tracking the Message: Applying Single Molecule Localization Microscopy to Cellular RNA Imaging.

RNA function is increasingly appreciated to be more complex than merely communicating between DNA sequence and protein structure. RNA localization has emerged as a key contributor to the intricate roles RNA plays in the cell, and the link between dysregulated spatiotemporal localization and disease warrants an exploration beyond sequence and structure. However, the tools needed to visualize RNA with precise resolution are lacking in comparison to methods available for studying proteins. In the past decade, many techniques have been developed for imaging RNA, and in parallel super resolution and single-molecule techniques have enabled imaging of single molecules in cells. Of these methods, single molecule localization microscopy (SMLM) has shown significant promise for probing RNA localization. In this review, we highlight current approaches that allow super resolution imaging of specific RNA transcripts and summarize challenges and future opportunities for developing innovative RNA labeling methods that leverage the power of SMLM.

Untangling Macropore Formation and Current Facilitation in P2X7.

Macropore formation and current facilitation are intriguing phenomena associated with ATP-gated P2X7 receptors (P2X7). Macropores are large pores formed in the cell membrane that allow the passage of large molecules. The precise mechanisms underlying macropore formation remain poorly understood, but recent evidence suggests two alternative pathways: a direct entry through the P2X7 pore itself, and an indirect pathway triggered by P2X7 activation involving additional proteins, such as TMEM16F channel/scramblase. On the other hand, current facilitation refers to the progressive increase in current amplitude and activation kinetics observed with prolonged or repetitive exposure to ATP. Various mechanisms, including the activation of chloride channels and intrinsic properties of P2X7, have been proposed to explain this phenomenon. In this comprehensive review, we present an in-depth overview of P2X7 current facilitation and macropore formation, highlighting new findings and proposing mechanistic models that may offer fresh insights into these untangled processes.

Diazaquinomycin Biosynthetic Gene Clusters from Marine and Freshwater Actinomycetes.

Tuberculosis is an infectious disease of global concern. Members of the diazaquinomycin (DAQ) class of natural products have shown potent and selective activity against drug-resistant Mycobacterium tuberculosis. However, poor solubility has prevented further development of this compound class. Understanding DAQ biosynthesis may provide a viable route for the generation of derivatives with improved properties. We have sequenced the genomes of two actinomycete bacteria that produce distinct DAQ derivatives. While software tools for automated biosynthetic gene cluster (BGC) prediction failed to detect DAQ BGCs, comparative genomics using MAUVE alignment led to the identification of putative BGCs in the marine Streptomyces sp. F001 and in the freshwater Micromonospora sp. B006. Deletion of the identified daq BGC in strain B006 using CRISPR-Cas9 genome editing abolished DAQ production, providing experimental evidence for BGC assignment. A complete model for DAQ biosynthesis is proposed based on the genes identified. Insufficient knowledge of natural product biosynthesis is one of the major challenges of productive genome mining approaches. The results reported here fill a gap in knowledge regarding the genetic basis for the biosynthesis of DAQ antibiotics. Moreover, identification of the daq BGC shall enable future generations of improved derivatives using biosynthetic methods.

Assessing patients' acceptance of their medication to reveal unmet needs: results from a large multi-diseases study using a patient online community.

BACKGROUND: Patients with chronic conditions are required to take long-term treatments for their disease itself or to prevent any potential health risks. Measuring patient acceptance of their medication should help to better understand and predict patients' behavior toward treatment. This study aimed to describe the level of patient acceptance toward various long-term treatments in real life using an online patient community. METHODS: This was an observational, cross-sectional study conducted through the French Carenity platform. All Carenity patient members were invited to complete an online questionnaire including the 25-item ACCEptance by the Patients of their Treatment (ACCEPT©) questionnaire. ACCEPT© measures patient acceptance toward their medication and includes one general acceptance dimension (Acceptance/General) and six treatment-attribute specific dimensions (scores 0-100; lowest to highest acceptance): Acceptance/Medication Inconvenience, Acceptance/Long-term Treatment, Acceptance/Regimen Constraints, Acceptance/Side effects, Acceptance/Effectiveness, and Acceptance/Numerous Medications. Patients included in the analysis were treated adults experiencing any chronic diseases and who responded to at least one ACCEPT© item. RESULTS: Among the 4193 patients included in the analysis, more than 270 chronic diseases were represented, amidst which 19 included more than 30 patients. Mean ACCEPT© Acceptance/General score for those 19 diseases were 61.2 (SD = 31.9) for type 1 diabetes, 59.8 (SD = 32.3) for asthma, 56.3 (SD = 34.3) for hypertension, 52.0 (SD = 32.2) for chronic obstructive pulmonary disease, 51.7 (SD = 27.0) for epilepsy, 50.1 (SD = 33.1) for bipolar disorder, 49.9 (SD = 33.1) for type 2 diabetes, 48.6 (SD = 31.6) for multiple sclerosis, 46.1 (SD = 34.5) for Crohn's disease/ulcerative colitis, 44.3 (SD = 31.5) for depression, 42.8 (SD = 31.5) for lupus, 42.3 (SD = 33.0) for arthrosis, 41.8 (SD = 32.6) for Parkinson's disease, 40.5 (SD = 32.2) for rheumatoid arthritis, 38.6 (SD = 31.7) for breast cancer, 36.4 (SD = 36.4) for myocardial infarction, 35.8 (SD = 32.0) for ankylosing spondylitis, 34.1 (SD = 32.3) for psoriasis, and 33.7 (SD = 31.7) for fibromyalgia. CONCLUSIONS: This first of its kind study enabled ACCEPT© data to be collected in real life for a variety of chronic diseases. These data may help in evaluating and interpreting levels of acceptance in future studies and provide valuable insights about patient priorities and current unmet needs.

Real-life assessment of the multidimensional nature of dyspnoea in COPD outpatients.

Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful.

Scoring and psychometric validation of the 'Determinants of Intentions to Vaccinate' (DIVA©) questionnaire.

BACKGROUND: Primary care physicians (PCPs) play a key role regarding vaccination in France. The aims of the present study were to define the scoring rules and to assess the measurement properties of the 'Determinants of Intentions to Vaccinate' (DIVA©) questionnaire that aims to assess PCPs' attitudes and beliefs toward vaccination. METHODS: The DIVA questionnaire was derived from a literature review and PCPs focus groups. Scoring and early validation of the DIVA questionnaire were determined during a cross-sectional study conducted in France. During the study, PCPs had to complete the DIVA questionnaire for any of the six vaccine-preventable diseases (VPDs) to which they were randomly assigned (measles, pertussis, pneumococcus infection, seasonal influenza, human papillomavirus -HPV- infection and tetanus). Descriptive analyses of items and the analysis of the grouping of items into domains were conducted. Internal consistency reliability and construct validity was assessed according to each VPD. RESULTS: The DIVA questionnaire was completed by 1,069 PCPs and was well accepted. The 'Commitment of the PCP to the vaccination approach' score showed very good internal consistency reliability (Cronbach's alpha >0.70 overall and for each VPD). The construct validity of the DIVA questionnaire was confirmed. CONCLUSIONS: The DIVA questionnaire is a valid and reliable measure of PCPs' attitudes and beliefs toward vaccination.

[The commitment of French general practitioners to vaccination: the DIVA study (Determinants of Vaccination Intentions)]. / L’engagement des médecins généralistes français dans la vaccination : l’étude DIVA (Déterminants des Intentions de Vaccination).

OBJECTIVES: Vaccination is an effective way to reduce morbidity and mortality related to infectious diseases. In France, primary care physicians are the main administrators of vaccines. Our objective was to conduct an exploratory qualitative study with primary care physicians to identify determinants of their commitment to vaccination. METHODS: A qualitative research study was conducted with 36 primary care physicians from different geographical regions in France. Six focus group discussions, following a semi-structured interview guide, were held. Qualitative analysis based on coding of the transcribed discussions was performed to identify the factors influencing primary care physicians' attitudes toward vaccination. These factors were then organized into themes. Saturation was also evaluated. RESULTS: Diphtheria, tetanus, poliomyelitis, measles, mumps, rubella, hepatitis B, tuberculosis, pneumococcal infections, meningococcus, human papillomavirus, rotavirus, pertussis, varicella and flu vaccinations were all discussed in each focus group. Saturation was reached from the fourth focus group. Forty identified determinants were divided into six themes: vaccine characteristics, disease characteristics, primary care physicians' past experience, practical aspects, expected benefits and primary care physician-patient relationship. CONCLUSIONS: This study identified the behavioural and organizational determinants influencing primary care physicians' attitudes toward vaccination. These attitudes and determinants varied according to diseases and vaccines. The identified determinants and themes were used as a basis for the development of a questionnaire evaluating the Determinant of Vaccination Intentions (DIVA) of primary care physicians.

How do Clostridium difficile infections affect nurses' everyday hospital work: A qualitative study.

This qualitative study explored the impact of Clostridium difficile infections on nurses' everyday work in the hospital. Twelve nurses (six in France and six in the United States) were interviewed in depth using a semi-structured interview guide. Thematic analysis of the interviews was performed. Managing diarrhoea and taking precautionary measures for infection control were the two most inconvenient aspects nurses reported with C. difficile patient management. Precautions included contact isolation, hand hygiene and reorganization/coordination of nursing care and ward. Precautions were time consuming and significantly increased nurses' workload when combined with caring for patients with uncontrollable, frequent bouts of diarrhoea. Management of C. difficile infection is extremely burdensome for nurses in their everyday work and disruptive to hospital organizations as a whole. Prevention of C. difficile infections, together with coordinated team work and communication, would therefore contribute to decreasing nurses' workload and the burden to health-care facilities associated with caring for these patients.

Improving the primary care physicians' decision making for fibromyalgia in clinical practice: development and validation of the Fibromyalgia Detection (FibroDetect®) screening tool.

BACKGROUND: Fibromyalgia diagnosis is a challenging and long process, especially among primary care physicians (PCPs), because of symptom heterogeneity, co-morbidities and clinical overlap with other disorders. The purpose was to develop and validate a screening tool in French (FR), German (DE) and English (UK) to help PCPs identify patients with fibromyalgia. METHODS: The FibroDetect questionnaire was simultaneously developed in FR, DE and UK based on information obtained from a literature review, focus groups conducted with clinicians, and face-to-face interviews with fibromyalgia patients (FR, DE and UK, n = 23). The resulting tool was comprehension-tested in patients with diagnosed or suspected fibromyalgia (n = 3 and n = 2 in each country, respectively). Acceptability and applicability were assessed and the tool modified accordingly, then assessed in clinical practice. A scoring method was created using an iterative process based on statistical and clinical considerations with American College of Rheumatology + (ACR+) patients and ACR- patients (n = 276), and validated with fibromyalgia and non-fibromyalgia patients (n = 312). RESULTS: The FibroDetect included 14 questions assessing patients' pain and fatigue, personal history and attitudes, symptoms and impact on lives. Six questions were retained in the final scoring, demonstrating satisfactory discriminative power between ACR + and ACR- patients with area under the Receiver Operating Characteristic curve of 0.74. The predictive accuracy of the tool increased to 0.86 for fibromyalgia and non-fibromyalgia patient detection, with a sensitivity of 90% and a specificity of 67% for a cut-off of 6 on the score. CONCLUSIONS: The FibroDetect is a self-administered tool that can be used as a screening classification surrogate to the ACR criteria in primary care settings to help PCPs detect potential fibromyalgia patients among a population complaining of chronic widespread pain.

Spatial visualization of A-to-I Editing in cells using Endonuclease V Immunostaining Assay (EndoVIA).

Adenosine-to-Inosine (A-to-I) editing is one of the most widespread post-transcriptional RNA modifications and is catalyzed by adenosine deaminases acting on RNA (ADARs). Varying across tissue types, A-to-I editing is essential for numerous biological functions and dysregulation leads to autoimmune and neurological disorders, as well as cancer. Recent evidence has also revealed a link between RNA localization and A-to-I editing, yet understanding of the mechanisms underlying this relationship and its biological impact remains limited. Current methods rely primarily on in vitro characterization of extracted RNA that ultimately erases subcellular localization and cell-to-cell heterogeneity. To address these challenges, we have repurposed Endonuclease V (EndoV), a magnesium dependent ribonuclease that cleaves inosine bases in edited RNA, to selectively bind and detect A-to-I edited RNA in cells. The work herein introduces Endonuclease V Immunostaining Assay (EndoVIA), a workflow that provides spatial visualization of edited transcripts, enables rapid quantification of overall inosine abundance, and maps the landscape of A-to-I editing within the transcriptome at the nanoscopic level.

Development of a questionnaire to assess the impact on parents of their infant's bronchiolitis hospitalization.

BACKGROUND: Bronchiolitis is a distressing respiratory condition and the most common cause of hospitalization during the first year of life. The hospitalization of an infant is a stressful event for parents and deserves careful consideration. The objective of this work was to develop and validate a self-administered instrument that comprehensively assesses the impact on parents of the hospitalization of their infant for bronchiolitis. METHODS: The Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©) was developed using a literature review and pre-study interviews with both parents and clinicians. For finalization and psychometric validation, it was included in a multicenter, longitudinal, observational study conducted in France. Parents of infants under the age of 1 year and hospitalized for bronchiolitis were asked to complete the questionnaire at hospital discharge, and 3 months after. RESULTS: Seven hundred and seven questionnaires were completed by the parents of the 463 eligible infants. After finalization, based on principal component analyses, the IBHQ included 30 core items allowing the calculation of 7 dimension core scores (Worries and distress; Fear for future; Guilt; Impact on daily organization; Physical impact; Impact on behavior with hospitalized infant; Financial impact), as well as 16 optional items, allowing the calculation of 5 optional dimension scores (Disturbed breastfeeding; Physical reaction of hospitalized infant; Impact on feeding; Impact on behavior with other infants; Siblings' reaction). Internal consistency reliability and construct validity of the IBHQ were satisfactory. The highest impact was observed for "Worries and distress", "Fear for future" and "Impact on daily organization" scores. CONCLUSIONS: The IBHQ is a reliable and valid instrument for assessing the multifaceted impact on parents of the hospitalization of their infant for bronchiolitis.

Validation of the Dutch version of the DN4 diagnostic questionnaire for neuropathic pain.

Difficulties in diagnosing neuropathic pain in routine clinical practice support the need for validated and easy-to-use diagnostic tools. The DN4 neuropathic pain diagnostic questionnaire aims to discriminate neuropathic pain from nociceptive pain, but needs clinical validation. A total of 269 patients with chronic pain in three pain clinics were included in the study of which 248 had analyzable data. The mean duration of pain was 4.9 years. The most frequent etiologies were posttraumatic (36%), (pseudo) radicular (14%), and mechanical back pain (12%). The mean intensity of pain at visit was 5.6 on a 0-10 scale. Hundred and ninety-six of 248 patients had an identical pain diagnosis from both physicians: 85 had neuropathic pain, 57 had nociceptive pain, and 54 had mixed pain. Among patients with identical diagnoses of neuropathic or nociceptive pain, using a receiver operating characteristic curve analysis, the area under the curve (AUC) was 0.81 for the DN4 7-item and 0.82 for the 10-item version. A cutoff point of 5/10 for the full questionnaire resulted in a sensitivity of 75% and a specificity of 79%, while a cutoff point of 4/7 for the partial questionnaire resulted in a sensitivity of 74% and a specificity of 79%. The items "brushing," "painful cold," and "numbness" were most discriminating. The DN4 is an easy-to-use screening tool that is reliable for discriminating between neuropathic and nociceptive pain conditions in daily practice. Item-specific scores provide important information in addition to the total score.

Optical control of PIEZO1 channels.

PIEZO proteins are unusually large, mechanically-activated trimeric ion channels. The central pore features structural similarities with the pore of other trimeric ion channels, including purinergic P2X receptors, for which optical control of channel gating has been previously achieved with photoswitchable azobenzenes. Extension of these chemical optogenetics methods to mechanically-activated ion channels would provide tools for specific manipulation of pore activity alternative to non-specific mechanical stimulations. Here we report a light-gated mouse PIEZO1 channel, in which an azobenzene-based photoswitch covalently tethered to an engineered cysteine, Y2464C, localized at the extracellular apex of the transmembrane helix 38, rapidly triggers channel gating upon 365-nm-light irradiation. We provide evidence that this light-gated channel recapitulates mechanically-activated PIEZO1 functional properties, and show that light-induced molecular motions are similar to those evoked mechanically. These results push the limits of azobenzene-based methods to unusually large ion channels and provide a simple stimulation means to specifically interrogate PIEZO1 function.

Dyspnea-induced Limitation (DYSLIM), a new self-administered concise questionnaire to evaluate dyspnea-related activity limitation in chronic respiratory diseases.

BACKGROUND AND AIM: Few questionnaires are available for routine assessment of dyspnea. The study aimed to design a self-administered questionnaire assessing the impact of chronic dyspnea on daily activities, named DYSLIM (Dyspnea-induced Limitation). METHODS: The development followed 4 steps: 1: selection of relevant activities and related questions (focus groups); 2: clinical study: internal and concurrent validity vs. modified Medical Research Council (mMRC), Baseline Dyspnea Index (BDI) and Saint George Respiratory Questionnaire (SGRQ); 3: item reduction; 4: responsiveness. Eighteen activities (from eating to climbing stairs) were considered with 5 modalities for each: doing the task slowly, taking breaks, seeking assistance, changing habits, and activity avoidance. Each modality was graded from 5 (never) to 1 (very often). Validation study included 194 patients: COPD (FEV1 ≥ 50% pred: n = 40; FEV1 < 50% pred: n = 65); cystic fibrosis (n = 30), interstitial lung disease (n = 30), pulmonary hypertension (n = 29). Responsiveness was evaluated by post-pulmonary rehabilitation data in 52 COPD patients. RESULTS: Acceptability was high and short term (7 days) reproducibility was satisfactory (Kappa mostly above 0.7). Concurrent validity was high vs. mMRC (Spearman correlation coefficient, r = 0.71), BDI (r = - 0.75) and SGRQ (r = - 0.79). The reduced questionnaire with 8 activities (from cleaning to climbing stairs) and 3 modalities (slowly, seeking help, changing habits) showed a comparable validity and was chosen as the final short version. Effect size of rehabilitation was good for both the full (0.57) and short (0.51) versions. A significant correlation was also found between changes of SGRQ and DYSLIM post rehabilitation: r = - 0.68 and r = - 0.60 for full and reduced questionnaires, respectively. CONCLUSION: The DYSLIM questionnaire appears promising for the evaluation of dyspnea-induced limitations in chronic respiratory diseases and seems suitable for use in various contexts.

Keratoconus and the Impact of Treatment on Patients' Quality of Life: A Qualitative Study.

INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

Appraisal of patient-reported outcome instruments available for randomized clinical trials in dry eye: revisiting the standards.

Clinical signs in dry eye (DE) often underestimate the severity of the condition, correlating poorly with symptoms and the impact on patients' health-related quality of life (HRQL). Patient-reported outcome (PRO) questionnaires are therefore essential to accurately evaluate the health status of DE patients and the severity of their condition. A comprehensive evaluation of HRQL in addition to clinical signs and visual function is necessary to fully characterize the impact of DE on patients' health. Growing interest in PRO measures and their implementation in clinical trials has resulted in more formal guidance on the design and properties of these instruments. To be scientifically sound and accepted by regulatory authorities, an instrument's development process and its appropriateness for use in the target population, its psychometric properties and responsiveness must be described. To address the recent health authority guidance, this review discusses the design, development methodology, and performance of currently available PRO instruments for DE.

Impact on parents of bronchiolitis hospitalization of full-term, preterm and congenital heart disease infants.

BACKGROUND: The objective of this work was to explore the impact on parents of the bronchiolitis hospitalization of their infant using the Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©). METHODS: Four hundred sixty-three infants aged less than 1 year and hospitalized for bronchiolitis were included in a French observational study during the 2008-2009 season. Parents were asked to complete the IBHQ at hospital discharge and 3 months later. IBHQ scores, ranging from 0 (no impact) to 100 (highest impact), were compared according to gestational age (full-term, 33-36 wGA, ≤ 32 wGA) and the presence of congenital heart disease (CHD). The potential drivers of impact were explored using multivariate linear regressions. RESULTS: The study included 332 full-terms, 71 infants born at 33-36 wGA, and 60 at ≤ 32 wGA; 28 infants had a CHD. At hospital discharge, 9 of the 12 IBHQ mean scores were above 40, indicating a marked impact on parents. Three months later, all mean scores were lower but 5 were still greater than 40. At discharge, the length of hospitalization had a significant effect on IBHQ worries and distress, fear for future, guilt and impact on daily organization scores (p<0.01); the parents' educational level had a significant effect on IBHQ worries and distress, fear for future, impact on daily organization and financial impact scores (p<0.05). The only statistically significant difference found between the parents of preterm and full-term infants was for the physical impact score at discharge (p=0.004). CONCLUSIONS: Bronchiolitis hospitalization has conspicuous emotional, physical and organizational consequences on parents and siblings, which persist 3 months after hospital discharge. The main drivers of the impact were length of hospital stay and parents' educational level, while infants' gestational age or the presence of a CHD had little influence.

The impact of childhood acute rotavirus gastroenteritis on the parents' quality of life: prospective observational study in European primary care medical practices.

BACKGROUND: Rotavirus (RV) is the commonest cause of acute gastroenteritis in infants and young children worldwide. A Quality of Life study was conducted in primary care in three European countries as part of a larger epidemiological study (SPRIK) to investigate the impact of paediatric rotavirus gastroenteritis (RVGE) on affected children and their parents. METHODS: A self-administered questionnaire was linguistically validated in Spanish, Italian and Polish. The questionnaire was included in an observational multicentre prospective study of 302 children aged <5 years presenting to a general practitioner or paediatrician for RVGE at centres in Spain, Italy or Poland. RV infection was confirmed by polymerase chain reaction (PCR) testing (n = 264). The questionnaire was validated and used to assess the emotional impact of paediatric RVGE on the parents. RESULTS: Questionnaire responses showed that acute RVGE in a child adversely affects the parents' daily life as well as the child. Parents of children with RVGE experience worry, distress and impact on their daily activities. RVGE of greater clinical severity (assessed by the Vesikari scale) was associated with higher parental worries due to symptoms and greater changes in the child's behaviour, and a trend to higher impact on parents' daily activities and higher parental distress, together with a higher score on the symptom severity scale of the questionnaire. CONCLUSIONS: Parents of a child with acute RVGE presenting to primary care experience worry, distress and disruptions to daily life as a result of the child's illness. Prevention of this disease through prophylactic vaccination will improve the daily lives of parents and children.

The SPUR adherence profiling tool: preliminary results of algorithm development.

OBJECTIVE: The SPUR (Social, Psychological, Usage, and Rational) Adherence Profiling Tool is a recently developed adaptive instrument for measuring key patient-level risk factors for adherence problems. This study describes the SPUR questionnaire's psychometric refinement and evaluation. METHODS: Data were collected through an online survey among individuals with type 2 diabetes in the United States. 501 participants completed multiple questionnaires, including SPUR and several validated adherence measures. A Partial Credit Model (PCM) analysis was performed to evaluate the structure of the SPUR tool and verify the assumption of a single underlying latent variable reflecting adherence. Partial least-squares discriminant analyses (PLS-DA) were conducted to identify which hierarchically-defined items within each dimension needed to be answered by a given patient. Lastly, correlations were calculated between the latent trait of SPUR adherence and other patient-reported adherence measures. RESULTS: Of the 45 candidate SPUR items, 39 proved to fit well to the PCM confirming that SPUR responses reflected one underlying latent trait hypothesized as non-adherence. Correlations between the latent trait of the SPUR tool and other adherence measures were positive, statistically significant, and ranged from 0.32 to 0.48 (p-values < .0001). The person-item map showed that the items reflected well the range of adherence behaviors from perfect adherence to high levels of non-adherence. The PLS-DA results confirmed the relevance of using four meta-items as filters to open or close subsequent items from their corresponding SPUR dimensions. CONCLUSIONS: The SPUR tool represents a promising new adaptive instrument for measuring adherence accurately and efficiently using the digital behavioral diagnostic tool.

Finalization and Validation of Questionnaire and Algorithm of SPUR, a New Adherence Profiling Tool.

Purpose: The SPUR (Social, Psychological, Usage and Rational) Adherence Profiling Tool is a recently developed adaptive instrument for assessing key patient-level drivers for non-adherence. This study describes the SPUR questionnaire's finalization and psychometric evaluation. Patients and Methods: Data were collected through an online survey among patients with type 2 diabetes included by general practitioners and diabetologists in France. The survey included four questionnaires, SPUR and three validated adherence measures: BMQ, MARS and ACCEPT. Item-level analysis and a partial credit model (PCM) were performed to refine the response option coding of SPUR items. The final item selection of SPUR was defined using a PCM and a principal component analysis (PCA). Construct validity, concurrent validity and known-groups validity were assessed on the final SPUR questionnaire. Results: A total of 245 patients (55% men, mean age of 63 years) completed the survey remotely and were included in this analysis. Refining response option coding allowed a better discrimination of patients on the latent trait. After item selection, a short, an intermediate, and a long form composed the final SPUR questionnaire. The short form will be used to screen patients for risk and then the other forms will allow the collection of further information to refine the risk assessment and decide the best levers for action. Results obtained were supportive of the construct validity of the forms. Their concurrent validity was demonstrated: moderate to high significant correlations were obtained with BMQ, MARS and ACCEPT scores. Their known-groups validity were shown with a logical pattern of higher scores obtained for patients considered non-adherent and significant differences between the scores obtained for patients considered adherent versus non-adherent. Conclusion: SPUR is a valid tool to evaluate the risk of non-adherence of patients, allowing effective intervention by providing insights into the respective individual reasons for lack of adherence.