Patient-reported experiences with refractory or unexplained chronic cough: a qualitative analysis.

BACKGROUND: Chronic cough, defined as a cough lasting 8 or more weeks, affects up to 10% of adults. Refractory chronic cough (RCC) is a cough that is uncontrolled despite comprehensive investigation and treatment of comorbid conditions while unexplained chronic cough (UCC) is a cough with no identifiable cause despite extensive evaluation of comorbid conditions. RCC and UCC are often poorly controlled. Understanding individuals' lived experience of the symptoms and impacts of these conditions may guide therapeutic strategies. OBJECTIVES: The primary objectives of this study were to assess respondents' perceptions of the key symptoms of RCC and UCC and the impacts of RCC and UCC and their symptoms on well-being, health-related quality of life, work productivity, and social relationships. DESIGN: Qualitative study. METHODS: This study enrolled 30 adults with physician-diagnosed RCC or UCC. Two trained qualitative researchers conducted individual, in-depth telephone interviews using a semi-structured interview guide. Interviews were audio-recorded, transcribed, coded, and systematically analyzed to identify content themes. RESULTS: A total of 15 respondents with RCC and 15 with UCC were included in the study. Many respondents had RCC or UCC for a long duration (median 9 years, range: 0-24). Half of the respondents reported having a coughing episode at least once daily. Only 40% of respondents reported that medication had improved their symptoms. In over half of the respondents, RCC or UCC hindered communication, caused embarrassment, frustration, and worry, and lowered quality of life. Perceptions of meaningful treatment benefits in RCC or UCC varied widely across respondents. CONCLUSION: RCC and UCC remained poorly managed in many individuals and were associated with a wide range of symptoms and cough triggers that hindered daily activities and reduced emotional well-being. Understanding individuals' lived experiences may inform the development of RCC and UCC therapeutic strategies.

Patient-reported experiences with refractory or unexplained chronic cough: a qualitative analysisChronic cough, particularly refractory and unexplained chronic cough, remain poorly managed in many individuals and are associated with a wide range of symptoms and cough triggers that hinder daily activities and reduce emotional well-being. Currently there are no US Food and Drug Administration-approved treatments for refractory or unexplained chronic cough. Understanding the experience and treatment preferences of individuals with these conditions may help inform the development of new therapies and clarify the potential impact of such therapies on the lives of individuals with chronic cough. Using in-depth interviews, the present study comprehensively evaluated individuals' experience with refractory or unexplained chronic cough and treatment priorities, a research area that has not been well-studied. This study detailed broad-ranging physical, behavioral, and emotional impacts of chronic cough, which hindered individuals' social well-being.

Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II.

BACKGROUND: Approximately two-thirds of patients with mucopolysaccharidosis II (MPS II) have a severe, neuronopathic phenotype, characterized by somatic, cognitive, and behavioral issues. Current standard of care for the treatment of MPS II is enzyme replacement therapy with intravenous recombinant human iduronate-2-sulfatase (idursulfase). To target cognitive manifestations of MPS II, idursulfase has been formulated for intrathecal administration into the cerebrospinal fluid (idursulfase-IT). In accordance with recommendations for patient-focused drug development, semi-structured interviews were conducted to assess caregiver experiences and observations in a 52-week phase 2/3 trial of idursulfase-IT, in addition to intravenous idursulfase in pediatric patients with neuronopathic MPS II, or a substudy which enrolled patients younger than 3 years old, all of whom received idursulfase-IT. RESULTS: Overall, 46 caregivers providing care for 50 children (mean [range] age 7.9 [3-17] years at interview) took part in a single 60-min exit interview; six of these children had participated in the substudy. Qualitative and quantitative data were obtained demonstrating the burden of MPS II experienced by caregivers and their families. Following participation in the trials, 39 (78%) of the children were reported by their caregivers to have experienced improvements in the symptoms and impact of disease. Of those with improvements, 37 (95%) experienced cognitive improvements and 26 (67%) experienced emotional/behavioral improvements. Overall, 43 children (86%) were rated by caregivers as having moderate or severe symptoms before the trials; after the trials, 28 children (56%) were considered to have mild or no symptoms. For the six children who participated in the substudy, these proportions were 83% and 100%, respectively. Caregivers' qualitative descriptions of trial experiences suggested improvements in children's verbal and non-verbal functioning and spatial and motor skills, as well as a positive impact on family life. CONCLUSIONS: This study revealed caregiver-reported improvements in children's MPS II symptoms and the impact of the disease on patients and their families. There was a trend for cognitive improvement and a reduction in severity of MPS II symptoms. After many years of extensive review and regulatory discussions of idursulfase-IT, the clinical trial data were found to be insufficient to meet the evidentiary standard to support regulatory filings.

Psychometric evaluation of the respiratory syncytial virus infection, intensity and impact questionnaire (RSV-iiiQ) in adults.

BACKGROUND: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ. METHODS: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed. RESULTS: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory. CONCLUSIONS: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.

Evaluating Elements of the Care Partner Experience in Individuals Who Care for People with Alzheimer's Disease Across the Severity Spectrum.

INTRODUCTION: Non-professional care partners play an important and often evolving role in the care of persons living with Alzheimer's disease (PLWAD). We investigated two elements of the care partner experience, namely time and strain incurred by care partners providing care to PLWAD across the severity spectrum. METHODS: Data gathered from the Alzheimer's Disease Patient and Caregiver Engagement (AD PACE) What Matters Most (WMM) study series were analyzed to determine how much time care partners spent providing care to PLWAD based on where the care recipients lived. Additionally, quantitative assessments of weekly hours providing care and the strain experienced by care partners were conducted using the UsAgainstAlzheimer's A-LIST Insights Series survey, which included the Modified Caregiver Strain Index (MCSI). Finally, a targeted literature review was conducted to contextualize findings and characterize the existing literature landscape. RESULTS: Care partners in the AD PACE WMM studies (n = 139) spent significantly more hours providing care for recipients who lived with someone (mean ± standard deviation [SD], 57.3 ± 44.3 h/week) than for recipients who lived alone (26.0 ± 12.0 h/week) (P = 0.0096) or lived in assisted living/nursing home (23.6 ± 14.4 h/week) (P = 0.0002). In the A-LIST Insights Series survey, care partners provided an overall mean (± SD) 58.1 ± 53.0 h of direct care each week, with caregiving hours increasing with increasing severity of AD/AD-related dementias (AD/ADRD). Additionally, care partners for recipients with mild (n = 14), moderate (n = 111), and severe AD/ADRD (n = 91) had overall mean MCSI scores of 9.0 ± 3.8 (range 2-14), 13.3 ± 4.8 (range 4-23), and 17.5 ± 5.3 (range 4-26), respectively, with higher scores suggesting greater care partner strain. CONCLUSIONS: Persons living with AD require increasing levels of care along the spectrum of disease, and even individuals with early disease need care from partners. Early interventions that slow progression of AD and programs that improve family function may have beneficial impact on the experiences of care partners for recipients with mild, moderate, or severe AD.

Psychometric evaluation of an electronic Asthma Symptom Diary for young children.

BACKGROUND: Patient-reported outcome measures that facilitate self-report by children are needed to reduce the bias of proxy report. We previously developed an electronic Pediatric Asthma Symptom Diary (ePASD) to assess the severity of daily asthma symptoms and proximal impacts in children aged 6-11 years with mild to severe asthma. The ePASD, administered via a digital application with visuals, sounds, and text, is uniquely designed to minimize the importance of reading skills on children's ability to self-report accurately. Here, we describe the ePASD's psychometric properties. METHODS: Ninety-one children aged 6-11 years with mild to severe asthma and their caregivers participated in 2 study visits, which consisted of training on the provisioned device and completing asthma-specific clinical outcome assessment (COA) questionnaires. The children self-completed the ePASD at home twice daily for 8 consecutive days. The scoring of the ePASD was guided by factor analyses, inter-item correlations, and internal consistencies. Reliability, discriminating ability, construct validity, and responsiveness were evaluated for ePASD items and candidate scores. RESULTS: All COAs included in the study-the ePASD, Asthma Control Questionnaire (ACQ), Childhood Asthma Control Test, Pediatric Asthma Quality of Life Questionnaire-Standardized (PAQLQ[S]), and global ratings-demonstrated that the children exhibited few asthma-related symptoms and impacts at all timepoints, and consequently, showed little change over time. Internal consistencies (all Cronbach's alphas ≥ 0.52) and test-retest reliabilities (all intraclass correlation coefficients ≥ 0.60) were largely satisfactory. Patterns of convergent and divergent correlations supported the construct validity of ePASD scores. The ePASD symptom scores correlated moderately to strongly with PAQLQ(S) Symptom scores (all correlations ≥ - 0.46) and with ACQ scores (all correlations ≥ 0.42), as predicted. Evidence of the discriminating ability of ePASD items and composite scores was demonstrated by known-groups analyses. CONCLUSIONS: The ePASD is a reliable and valid measure of asthma symptoms and proximal impacts in children aged 6-11 years with mild, moderate, or severe asthma. These results lay the psychometric groundwork for use of the ePASD in future clinical trials for the management of pediatric asthma. An ongoing pediatric asthma treatment trial is anticipated to provide evidence of the ePASD's responsiveness to change.

Qualitative assessment of the patient experience of primary hyperoxaluria type 1: an observational study.

BACKGROUND: Without effective intervention, primary hyperoxaluria type 1 (PH1) causes oxalate-induced kidney damage, leading to end-stage kidney disease and serious complications throughout the body. Although PH1 carries a heavy burden that impacts quality of life, literature on the experiences of those living with PH1 and caring for patients with PH1 is limited. This study aimed to describe the diagnostic journey in PH1 and characterize patients' and caregivers' self-reported experiences throughout the disease course. METHODS: This was an observational study involving in-depth, semi-structured telephone interviews. Dominant trends were assessed using constant comparative analysis to identify themes in interviewees' descriptions of their experiences. Individuals aged ≥ 12 years and caregivers of children aged 6-17 years with genetically confirmed PH1 were eligible. Informed consent/assent and ability to read and speak English were required. RESULTS: Interviewees (16 patients, 12 caregivers) reported a prolonged diagnostic journey due to low disease awareness, among other factors. Upon diagnosis, PH1 was frequently symptomatic, typically involving kidney stone-related symptoms but also potentially symptoms arising beyond the kidneys. PH1 most commonly led to worry and social impairment in adolescents, impaired physical function in adults, and a range of impacts on caregivers. In late-stage disease, dialysis was the most burdensome aspect of living with PH1 (due to time requirements, limitations from living with a catheter, etc.), and this burden was exacerbated by the COVID-19 pandemic. Benefits desired from PH1 management included reductions in laboratory measures of oxalate burden, kidney stone and urination frequency, and oxalate-related skin ulcers. CONCLUSIONS: PH1 greatly impacts patients' and caregivers' lives, primarily due to burdensome disease manifestations and associated emotional, physical, and practical impacts, as well as disease management challenges - particularly those related to dialysis in late-stage disease.

Relationship between clinical-epidemiological parameters and outcomes of patients with COVID-19 admitted to the intensive care unit: a report from a Brazilian hospital.

Background: People in low-income countries, especially those with low socio-economic conditions, are likelier to test positive for SARS-CoV-2. The unequal conditions of public health systems also increase the infection rate and make early identification and treatment of at-risk patients difficult. Here, we aimed to characterize the epidemiological profile of COVID-19 patients in intensive care and identify laboratory and clinical markers associated with death. Materials and methods: We conducted an observational, descriptive, and cross-sectional study in a reference hospital for COVID-19 treatment in the Southern Region of Bahia State, in Brazil, to evaluate the epidemiological, clinical, and laboratory characteristics of COVID-19 patients admitted to the intensive care unit (ICU). Additionally, we used the area under the curve (AUC) to classify survivors and non-survivors and a multivariate logistic regression analysis to assess factors associated with death. Data was collected from the hospital databases between April 2020 and July 2021. Results: The use of bladder catheters (OR 79.30; p < 0.0001) and central venous catheters (OR, 45.12; p < 0.0001) were the main factors associated with death in ICU COVID-19 patients. Additionally, the number of non-survivors increased with age (p < 0.0001) and prolonged ICU stay (p < 0.0001). Besides, SAPS3 presents a higher sensibility (77.9%) and specificity (63.1%) to discriminate between survivors and non-survivor with an AUC of 0.79 (p < 0.0001). Conclusion: We suggest that multi-laboratory parameters can predict patient prognosis and guide healthcare teams toward more assertive clinical management, better resource allocation, and improved survival of COVID-19 patients admitted to the ICU.

Exploring Personal Recovery in Schizophrenia: The Role of Mentalization.

Recovery is a broadly debated concept in the field of psychiatry research and in schizophrenia. Our study aims to understand the correlation between personal recovery from schizophrenia and factors such as mentalization, disability, quality of life, and antipsychotic side effects; Methods: Participants with schizophrenia (according to DSM-5 criteria) were consecutively recruited from the Psychiatry Unit of the University of Catania, Italy. Participants were assessed with the Recovery Assessment Scale (RAS), the Multidimensional Mentalizing Questionnaire (MMQ), the brief version of the WHO Disability Assessment Schedule (WHO-DAS), the EuroQoL-5 dimensions-5 levels, the Insight Orientation Scale (IOS) and the Glasgow Antipsychotic Side Effect Scale (GASS); Results: 81 patients were included. Our findings showed a positive correlation between RAS total scores and MMQ scores, especially in "good mentalizing" subdomains. IOS scores also had a positive association with RAS and MMQ scores. In contrast, poor mentalizing abilities negatively correlated with WHO-DAS 2.0 scores. While antipsychotic side effects influenced functioning, they did not impact perceived recovery. Conclusions: The study's results identified potential predictors of personal recovery from schizophrenia. These findings could contribute to creating tailored interventions to facilitate the recovery process.

Psychometric evaluation of the Symptoms of Infection with Coronavirus-19 (SIC): results from a cross-sectional study and a phase 3 clinical trial.

BACKGROUND: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and longitudinal psychometric evaluations, qualitative exit interviews were conducted to support the content validity of the SIC. METHODS: In a cross-sectional study, adults diagnosed with COVID-19 in the United States completed the web-based SIC and additional PRO measures. A subset was invited to participate in phone-based exit interviews. Longitudinal psychometric properties were assessed in ENSEMBLE2, a multinational, randomized, double-blind, placebo-controlled, phase 3 trial of the Ad26.COV2.S COVID-19 vaccine. Psychometric properties evaluated included structure, scoring, reliability, construct validity, discriminating ability, responsiveness, and meaningful change thresholds of SIC items and composite scores. RESULTS: In the cross-sectional study, 152 participants completed the SIC (mean age, 51.0 ± 18.6 years) and 20 completed follow-up interviews. Fatigue (77.6%), feeling unwell (65.8%), and cough (60.5%) were symptoms most frequently reported. SIC inter-item correlations were all positive and mostly moderate (r ≥ 0.3) and statistically significant. SIC items and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) scores correlated as hypothesized (all r ≥ 0.32). Internal consistency reliabilities of all SIC composite scores were satisfactory (Cronbach's alpha, 0.69-0.91). SIC composite scores correlated moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) with PROMIS-29 scores and Patient Global Impression of Severity (PGIS) ratings (all P < 0.01). A variety of signs/symptoms were cited in exit interviews, and participants considered the SIC straightforward, comprehensive, and easy to use. From ENSEMBLE2, 183 participants with laboratory-confirmed moderate to severe/critical COVID-19 were included (51.5 ± 14.8 years). Strong test-retest reliabilities were observed for most SIC composite scores (intraclass correlations ≥ 0.60). Statistically significant differences across PGIS severity levels were found for all but 1 composite score, supporting known-groups validity. All SIC composite scores demonstrated responsiveness based on changes in PGIS. CONCLUSIONS: The psychometric evaluations provided strong evidence for the reliability and validity of the SIC for measuring COVID-19 symptoms, supporting its use in vaccine and treatment trials. In exit interviews, participants described a broad range of signs/symptoms consistent with previous research, further supporting the content validity and format of the SIC.

Coronavirus disease 2019 (COVID-19) is a serious disease that continues to evolve globally. Researchers developed the Symptoms of Infection with Coronavirus-19 (SIC), a 30-item questionnaire designed for patients to report signs and symptoms of COVID-19. In this study, the researchers formally analyzed how well the SIC measures the patient experience with COVID-19, using survey and clinical trial data as well as telephone interviews. Adults with COVID-19 and at least 2 bothersome symptoms completed the web-based survey, and some of these individuals also participated in in-depth interviews. Participants in a clinical trial for a COVID-19 vaccine also completed the SIC measure. The SIC was compared with other commonly used questionnaires that evaluate patient experience. The most commonly reported symptoms of COVID-19 were fatigue, feeling unwell, cough, weakness, and headache. The items for individual symptoms (e.g., "cough") and combined scores for body systems (e.g., "respiratory system") performed well in statistical analyses. Participants found the SIC to be straightforward, comprehensive, and easy to use. The SIC may prove useful in the future for vaccine and treatment trials for COVID-19.

Assessing the patient experience of respiratory syncytial virus infection: development of a patient-reported outcome measure.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in older adults. Despite a number of RSV vaccine candidates in clinical trials, there are no existing disease-specific, self-reported measures that assess the symptoms and severity of RSV infection from the perspective of adult patients with acute RSV. The objective of this study was to describe the initial conceptualization and development of the RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ), a new patient-reported outcome measure. METHODS: A targeted review of the literature identified relevant existing measures, symptoms, and impacts of RSV. A draft version of the RSV-iiiQ was developed based on the Influenza Intensity and Impact Questionnaire (Flu-iiQ) with expert input. Qualitative interviews (N = 20) were conducted with participants to optimize the RSV-iiiQ conceptual model and confirm the content validity of the RSV-iiiQ. Interviews included concept elicitation and a cognitive debriefing assessment. A draft conceptual framework was developed, and the electronic clinical outcome assessment was piloted. All steps of instrument development followed Food and Drug Administration guidance for patient-reported outcomes. RESULTS: In-depth concept elicitation interviews followed by cognitive debriefings demonstrated that the content of the items was comprehensive, covered the breadth of RSV symptoms and impacts, and was relevant to the experiences of individuals with RSV. Both the paper and electronic versions of the RSV-iiiQ were easily completed. Minor refinements were made to some items based on participant feedback, and the draft conceptual framework was refined. CONCLUSIONS: The RSV-iiiQ was developed for use in clinical trials to measure the symptom intensity and impact of acute RSV infection from the perspective of adult patients. The tool was developed in accordance with current regulatory guidance and is useful to support patient-focused drug development.

Cupuassu juice fermentation by Lactiplantibacillus plantarum Lp62 produces an antioxidant enriched probiotic beverage.

The present work aimed to produce a cupuassu juice (Theobroma grandiflorum) fermented by the probiotic bacterium Lactiplantibacillus plantarum Lp62 and to analyze its antioxidant potential, antimicrobial activity, and resistance to biological barriers. The fermented beverage showed an increase in the content of phenolics, flavonoids, and antioxidant potential. The culture showed antagonistic activity against pathogens, but this result was not observed when the juice was tested. The probiotic strain remained viable under refrigeration, even in an acidified environment, and survived simulated gastrointestinal transit in vitro. L. plantarum Lp62 showed 30% adherence to HT-29 intestinal cells and proved to be safe in terms of antibiotic resistance and production of virulence factors. Fermentation increased the functional characteristics of cupuassu juice. This drink proved to be a good vehicle for the delivery of the probiotic bacteria L. plantarum Lp62.

Technical Review of Clinical Outcomes Assessments Across the Continuum of Alzheimer's Disease.

INTRODUCTION: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. METHODS: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. RESULTS: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. CONCLUSION: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.

Assessing What Matters to People Affected by Alzheimer's Disease: A Quantitative Analysis.

INTRODUCTION: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. METHODS: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). RESULTS: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. CONCLUSION: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes.

Development of patient- and observer-reported outcome measures to assess COVID-19 signs and symptoms in children and adolescents.

BACKGROUND: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome measure to evaluate the presence and severity of COVID-19 signs/symptoms in adults. This study expanded the context of use of the adult SIC among adolescents aged 12-17 years and supported a pediatric adaptation (the Pediatric SIC [PedSIC]) for caregiver assessment of signs/symptoms in children aged < 12 years. METHODS: Draft versions of the PedSIC and reference materials containing sign/symptom definitions for adolescents, based on an assessment of the reading level of SIC items by a professional linguist, were developed to facilitate accurate completion of the SIC by adolescents and observer-report (PedSIC) by caregivers. For adolescents, reference materials were intended to provide definitions for selected signs/symptoms identified to have a higher reading level. Iterative rounds of cognitive debriefing interviews were conducted from November 2020 to January 2021 to evaluate adolescent understanding of the SIC reference materials and inform refinement of the PedSIC for caregivers of children too young to reliably self-report. Participants were identified via databases of individuals who previously expressed interest in participating in qualitative research and were then screened for eligibility. Recruitment quotas were established to improve sample diversity. Thematic analysis and descriptive statistics were used to assess qualitative and demographic data, respectively. RESULTS: Nine healthy adolescents (mean [SD, range] age, 14 [1.76, 12-17] years, 56% female, 22% non-White; round 1, n = 6; round 2, n = 3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26-41] years, 59% female, 35% non-White; round 1, n = 9; round 2, n = 8) were interviewed. Adolescents understood the majority of signs/symptoms (22 of the 30 SIC items) without assistance or use of the reference materials during the cognitive debriefing interview. Definitions were added to the reference materials for 5 additional items, and clarifications provided to existing definitions for 3 items. Seven observer-report (PedSIC) items were modified following feedback from caregivers of healthy young children. Reference materials (similar to those for adolescent use) were developed to support caregiver understanding of the intent of the PedSIC items collecting input from children ages ≥ 5- < 12 years. CONCLUSIONS: Results support using the SIC, PedSIC, and their associated reference materials to evaluate the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years via caregiver-supported report, respectively.

In vitro selection and characterization of probiotic properties in eight lactobacillus strains isolated from cocoa fermentation.

Traditionally, probiotic microorganisms are isolated from human and animal intestinal microbiota. However, the demand for diversification of biofunctional products has driven the search for new sources of probiotic candidates, such as fermented foods and vegetables. The present study found that strains isolated from the fermentation of fine cocoa from southern Bahia have biotechnological potential for use as a probiotic, since they showed capacity for self-aggregation and co-aggregation, antimicrobial activity against intestinal pathogens and resistance to gastrointestinal transits. Scores of importance for each property were established in order to more accurately assess the probiotic potential of the strains. The tests carried out contemplate the criteria previously established for the selection of probiotic candidates.

Antagonistic activity of Lactiplantibacillus plantarum 6.2 extracted from cocoa fermentation and its supernatant on Gardnerella vaginalis.

Search for alternative methods for the treatment of bacterial vaginosis has been growing, and probiotics being among them. The most well-known probiotic microorganisms are lactobacilli, which are naturally present in the vaginal microenvironment. Cocoa fermentation is a source of lactic acid bacteria, with lactobacilli being the most prominent. The aim of this study was to evaluate the antagonistic activity of Lactiplantibacillus plantarum 6.2 a strain of lactobacilli isolated from cocoa fermentation, and its cell-free supernatant on Gardnerella vaginalis. It was shown that Lpb. plantarum 6.2 and its supernatant, used at three concentrations, i.e., 40, 20 and 10 mg/mL, have a strong antagonistic activity against G. vaginalis, with a probable action of proteinaceous bacteriocins; the activity was lost after heat treatment. The ability to exclude and displace G. vaginalis from the adhesion site to vaginal HMVII epithelial cells was also demonstrated by the lactobacilli and the supernatant, with the latter showing a bactericidal effect. Thus, the Lpb. plantarum 6.2 strain presents itself as a good probiotic with potential to be used not only as a therapeutic alternative for vaginosis but also as a complement to existing therapies.

Development of a novel patient-reported outcome measure to assess signs and symptoms of COVID-19.

BACKGROUND: Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development. METHODS: An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method. The measure was refined based on additional feedback from the clinicians and three iterative rounds of combined concept elicitation and cognitive debriefing interviews conducted with patients, caregivers, and healthy volunteers. RESULTS: Among 39 scientific articles identified in the literature review, 35 COVID-19 signs and symptoms were reported and confirmed during interviews with clinicians, patients, and caregivers. Patients and healthy participants suggested changes for refining the draft SIC to ensure consistent interpretation and endorsed both the 24-h recall period and use of an 11-point numeric rating scale (NRS) for capturing change in symptom severity. The final version of the SIC captures the daily presence or absence of 30 symptoms and a rating of severity for 25 of the 30 symptoms using an NRS for those symptoms reported as present. CONCLUSIONS: The SIC comprehensively addresses observations described in the literature, by clinicians, and by patients, and captures patients' experiences with COVID-19 in a manner that minimizes complexity and facilitates completion for both patients and healthy volunteers. This measure is thus appropriate for use in clinical trials of both therapeutics and vaccines for COVID-19.

Bioprotective potential of lactic acid bacteria and their metabolites against enterotoxigenic Escherichia coli.

Escherichia coli is one of the main pathogens that impacts swine production. Given the need for methods for its control, the in vitro effect of lactic acid bacteria (LAB) and their metabolites against E. coli F4 was evaluated through cell culture and microbiological analysis. The strains Limosilactobacillus fermentum 5.2, Lactiplantibacillus plantarum 6.2, and L. plantarum 7.1 were selected. To evaluate the action of their metabolites, lyophilized cell-free supernatants (CFS) were used. The effect of CFS was evaluated in HT-29 intestinal lineage cells; in inhibiting the growth of the pathogen in agar; and in inhibiting the formation of biofilms. The bioprotective activity of LAB was evaluated via their potential for autoaggregation and coaggregation with E. coli. The CFS did not show cytotoxicity at lower concentrations, except for L. fermentum 5.2 CFS, which is responsible for cell proliferation at doses lower than 10 mg ml-1. The CFS were also not able to inhibit the growth of E. coli F4 in agar; however, the CFS of L. plantarum 7.1 resulted in a significant decrease in biofilm formation at a dose of 40 mg ml-1. Regarding LAB, their direct use showed great potential for autoaggregation and coaggregation in vitro, thus suggesting possible effectiveness in animal organisms, preventing E. coli fixation and proliferation. New in vitro tests are needed to evaluate lower doses of CFS to control biofilms and confirm the bioprotective potential of LAB, and in vivo tests to assess the effect of LAB and their metabolites interacting with animal physiology.

Validation of the Glasgow Antipsychotic Side-Effect Scale (GASS) in an Italian Sample of Patients with Stable Schizophrenia and Bipolar Spectrum Disorders.

Antipsychotics are a class of psychotropic drugs that improve psychotic symptoms and reduce relapse risk. However, they may cause side effects (SE) that impact patients' quality of life and psychosocial functioning. Therefore, there is a need for practical tools to identify them and possibly intervene. The objective of the present study was to translate into Italian the Glasgow Antipsychotic Side Effect Scale (GASS), which is suggested as the questionnaire of choice to collect SE reported by patients treated with antipsychotics. We administered the GASS and the Udvalg for Kliniske Undersøgelser (UKU) SE scale-which is considered the gold standard-to 100 stable patients with schizophrenia and bipolar spectrum disorders. We measured the structural validity, internal consistency, concurrent criterion validity, construct validity, and clinical feasibility. GASS was characterized by modest structural validity and good internal consistency. The binary correlations concerning the presence of specific symptoms investigated with the GASS and the UKU were strong or relatively strong for only half of them. The GASS total scale score was inversely related to patients' quality of life and psychosocial functioning. The GASS is useful to briefly assess the burden of antipsychotic SE (~5 min) but is not optimal in identifying them.

Patient experiences with patient-reported outcome measures in metastatic breast cancer trials: qualitative interviews.

BACKGROUND: Patient-reported outcome (PRO) measures are critical for assessing treatment benefit of anticancer treatments. Although PRO measures have been developed with the intention of capturing patient-centric concepts, a gap exists in understanding the patient experience with these tools. We characterized the experience of patients with metastatic breast cancer (mBC) with PRO measures in an oncology clinical trial setting to determine the importance, relevance, barriers, and facilitators for PRO completion. METHODS: The multicenter, qualitative design included semistructured interviews with 18 women with mBC who completed PRO measures in a clinical trial setting within 1 year of screening. Interviews began with concept elicitation to understand symptom characterization, decision to participate in a clinical trial, pre-trial expectations, and thoughts on study-related questionnaires. Cognitive debriefing was conducted to determine if items in a commonly used PRO instrument were relevant to the patient experience. Qualitative data were analyzed using a constant comparative approach. RESULTS: Participants described the need for detailed explanation of PRO measures at study start, including information about how the PRO data will likely be used to support drug development. Respondents who felt connected to clinical trial research were more likely to feel as if the measures adequately captured their experiences. Items that were deemed irrelevant or out of date to the patient experience may cause a respondent to feel marginalized and adds to the overall burden of PRO measure completion. Mode of PRO measure administration (electronic/paper) was important to some, but placement of the instrument completion within a study visit appeared to influence respondent willingness to fully engage with the measures. A lack of any type of feedback loop to allow respondents to learn from the captured PRO data was noted as important but missing from the patient experience. CONCLUSIONS: PRO measures need to include content that is relevant to the patient experience over the course of the clinical trial period to be considered meaningful to respondents, and administration techniques also impact engagement. Robust communication strategies that socialize the intent, use, and results of PRO data may enrich the patient experience and support greater adherence to PRO completion in future studies.