Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth.

The experiments presented here are based on the reconfiguration of an ancient medicine, Lemnian Earth (LE) (terra sigillata, stamped earth, sphragis), an acclaimed therapeutic clay with a 2500-year history of use. Based on our hypothesis that LE was not a natural material but an artificially modified one involving a clay-fungus interaction, we present results from experiments involving the co-culture of a common fungus, Penicillium purpurogenum (Pp), with two separate clay slurries, smectite and kaolin, which are the principal constituents of LE. Our results show: (a) the leachate of the Pp+smectite co-culture is antibacterial in vitro, inhibiting the growth of both Gram-positive and Gram-negative bacteria; (b) in vivo, supplementation of regular mouse diet with leachates of Pp+smectite increases intestinal microbial diversity; (c) Pp+kaolin does not produce similar results; (d) untargeted metabolomics and analysis of bacterial functional pathways indicates that the Pp+smectite-induced microbiome amplifies production of short-chain fatty acids (SCFAs) and amino acid biosynthesis, known to modulate intestinal and systemic inflammation.

Outcome measures for migraine: Measuring the impact of migraine and results of migraine treatment.

The experience of migraine symptoms and the impacts of migraine on quality of life (QOL) are best reported by the person experiencing them. Therefore, patient-reported outcome (PRO) measures are often used to collect data about the experience and impact of migraine, and value of migraine treatments. PRO concepts that are assessed for the evaluation of migraine treatment outcomes are myriad and diverse (e.

Using Health-Related Social Media to Understand the Experiences of Adults With Lung Cancer in the Era of Immuno-Oncology and Targeted Therapies: Observational Study.

Background: The treatment of non-small cell lung cancer (NSCLC) has evolved dramatically with the approval of immuno-oncology (IO) and targeted therapies (TTs). Insights on the patient experience with these therapies and their impacts are lacking. Health-related social media has been increasingly used by patients to share their disease and treatment experiences, thus representing a valuable source of real-world data to understand the patient's voice and uncover potential unmet needs.

The Severity of Chronic Cough Diary (SCCD): development and content validation of a novel patient-reported outcome instrument for evaluating the symptom experience of chronic cough.

Background: Refractory chronic cough (RCC), a cough lasting longer than 8 weeks with an unexplained underlying etiology and unresponsive to conventional treatment, can have substantial effects on patients' quality of life. For assessment of the efficacy of antitussive medication in clinical trials in RCC, patient-reported outcome (PRO) instruments should be fit for purpose with appropriate content validity. Here we describe the qualitative testing of a newly developed PRO instrument: the Severity of Chronic Cough Diary (SCCD).

Validation of Spleen Shear Wave Elastography for the Screening of High-risk Varices in Patients with Compensated Advanced Chronic Liver Disease.

Objectives: Total number of avoided endoscopies using Baveno VI criteria is relatively low. Spleen elastography is an attractive tool and when compared with liver stiffness, it better represents the dynamic changes occurring in portal hypertension. The aim of the study was to evaluate spleen shear wave elastography (SWE) in compensated advanced chronic liver disease (cACLD) patients for ruling out the presence of esophageal high-risk varices (HRV).

Barrett's Esophagus: A Comparison Study between Two Cohorts of Gastroesophageal Reflux Disease.

Introduction: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD). It is seen among 15% of GERD patients as per a population-based study by Ronkainen et  al. Barrett's has malignant potential and annual progression to carcinoma depends on the presence or absence of dysplasia.

Assessment of Visceral Fat Volume and Its Correlation with the Severity of Hepatic Fibrosis in Patients with NAFLD.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease. The spectrum of NAFLD includes simple steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Our study aimed to calculate visceral fat volume at the L3-L4 vertebral level and its association with hepatic fibrosis assessed by transient elastography.

Developing a Conceptual Disease Model of Patient Experiences and Identifying Patient-Reported Clinical Outcome Assessments for Use in Trials of Treatments for Focal Onset Seizures.

Purpose: To identify concepts important to understanding the experiences of adults with focal onset seizures (FOS) and evaluate clinical outcome assessments (COAs) for measuring these concepts in clinical trials of treatments for FOS.

Methods: A search of published qualitative research, clinical trials, and approved product labels for FOS treatments was performed to develop a conceptual disease model (CDM) of patients' experience of living with FOS. Concepts of interest (COI) were selected, and a second literature search was conducted to identify COAs measuring these concepts.

Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials.

Objective: The purpose of this study was to examine changes in the functional impact of migraine following treatment with erenumab, as measured by the Migraine Functional Impact Questionnaire (MFIQ).

Background: The MFIQ, a novel patient-reported outcome (PRO) measuring the impact of migraine on four domains (physical function, social function, and emotional function [PF, SF, and EF]; usual activities [UAs]) and a single item assessing overall impact on UA, was included in phase III trials evaluating erenumab 70 and 140 mg monthly for migraine prevention among people with episodic migraine (EM).

Methods: In the ARISE study, 577 patients with EM were randomized to erenumab 70 mg or placebo.

Development of the SMA independence scale-upper limb module (SMAIS-ULM): A novel scale for individuals with Type 2 and non-ambulant Type 3 SMA.

Background: The amount of assistance required to perform daily activities for individuals with Type 2 and non-ambulant Type 3 spinal muscular atrophy (SMA) is often cited as meaningful for quality of life, and important to routinely assess.

Methods: The SMA Independence Scale (SMAIS), a patient-reported outcome measure for individuals with SMA aged ≥12 years, and an observer-reported outcome measure for caregivers of individuals aged ≥2 years, was developed and evaluated in two phases. In Phase 1, 30 draft items were developed following review of the literature.

Impact and burden of acid sphingomyelinase deficiency from a patient and caregiver perspective.

Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease (NPD) types A, A/B, and B, is a rare, progressive, potentially fatal lysosomal storage disease with a spectrum of phenotypes. Little is known about how ASMD symptoms affect the lives of patients and their caregivers. In a cross-sectional qualitative study conducted in the US and UK, and in collaboration with the National Niemann-Pick Disease Foundation (US) and Niemann-Pick UK, we investigated the symptom experience of patients with ASMD types B and A/B and explored how the disease impacts their and their caregivers' lives.

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine: A Focus Group Study.

Background: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients' perceptions towards them is limited.

Objective: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine.

Evaluating functional disability in clinical trials of lisdexamfetamine dimesylate in binge eating disorder using the Sheehan Disability Scale.

Objectives: This study examined Sheehan Disability Scale (SDS) performance in binge eating disorder (BED) and explored relationships between SDS and BED outcomes using data from three placebo-controlled lisdexamfetamine (LDX) studies (two short-term, dose-optimized studies and one double-blind, randomized-withdrawal study) in adults with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)-defined BED.

Methods: Analyses evaluated the psychometric properties of the SDS.

Results: Confirmatory factor analysis supported a unidimensional total score in the short-term studies, with internal consistency (Cronbach's α) being 0.

Quality of life, caregiver burden and mental health disorders in primary caregivers of patients with Cirrhosis.

Background And Aims: Caregivers are needed for cirrhotic patients as there is progressive decline in cognition and self-care. We intend to study the quality of life (QOL), psychosocial burden and prevalence of mental health disorders among caregivers.

Methods: Cross-sectional study where caregivers, defined as person who takes responsibility of providing care to patient, of cirrhotic patients were included.

Defining Patient Engagement in Research: Results of a Systematic Review and Analysis: Report of the ISPOR Patient-Centered Special Interest Group.

Objectives: Lack of clarity on the definition of "patient engagement" has been highlighted as a barrier to fully implementing patient engagement in research. This study identified themes within existing definitions related to patient engagement and proposes a consensus definition of "patient engagement in research."

Methods: A systematic review was conducted to identify definitions of patient engagement and related terms in published literature (2006-2018).

Assessing the impact on caregivers caring for patients with rare pediatric lysosomal storage diseases: development of the Caregiver Impact Questionnaire.

Background: Capturing the impact of caring for patients with debilitating rare disease is important for understanding disease burden. We aimed to develop and validate an instrument to measure the impact on caregivers of caring for children with three lysosomal storage diseases (LSDs): metachromatic leukodystrophy (MLD), neuronopathic mucopolysaccharidosis type II (MPS II) and mucopolysaccharidosis type IIIA (MPS IIIA).

Methods: A draft instrument was developed based on targeted literature searches and revised through sequential qualitative interviews with caregivers of patients first with MLD (n = 16), then with MPS II (n = 22), and finally with MPS IIIA (n = 8).

Evaluating the Psychometric Properties of the Migraine Functional Impact Questionnaire (MFIQ).

Background: Migraine is a chronic neurologic disease that can be associated with significant migraine-related impact, disability, and burden. Patient-reported outcome measures (PRO) are included in clinical trials of migraine interventions to capture treatment effects from a patient perspective. Clinical and regulatory guidelines also encourage use of PROs in trials.

Development of a New Tool for Evaluating the Benefit of Preventive Treatments for Migraine on Functional Outcomes - The Migraine Functional Impact Questionnaire (MFIQ).

Objective: The objective of this study was to develop a method for evaluating patient-relevant outcomes of interventions for preventing migraine attacks, followed by an assessment of the content validity of a new patient-reported outcome (PRO) instrument: the Migraine Functional Impact Questionnaire (MFIQ).

Background: The aim of preventive treatments for migraine is not only to reduce migraine frequency, but also to restore patients' ability to function and improve quality of life.

Methods: A multi-stage process based on best practice methods and regulatory guidelines for ensuring content validity of PRO instruments for evaluating treatment benefit was followed.

Evaluation of the psychometric properties of the Early Morning Symptoms of COPD Instrument (EMSCI).

Background: Early morning respiratory symptoms impact quality of life and are often the most troublesome for patients with COPD. Reduction in symptoms and their impact are important treatment outcomes for COPD. The Early Morning Symptoms of COPD Instrument (EMSCI) is a daily diary designed to collect patients' report of the occurrence, severity, and impact of morning COPD symptoms.

Development and exploration of the content validity of a patient-reported outcome measure to evaluate the impact of migraine- the migraine physical function impact diary (MPFID).

Background: Adults with migraine experience substantial reductions in quality of life during and in-between migraine attacks. Clinical and regulatory guidelines encourage the inclusion of patient reported outcomes for the evaluation of benefits of interventions for migraine.

Methods: The conceptual framework and items for a new patient-reported outcome (PRO) instrument, the Migraine Physical Function Impact Diary (MPFID), were developed using scientific methods recommended to ensure content validity of PRO instruments.

Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary.

Objective: The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient-reported outcome (PRO) measure for assessing the impact of migraine on physical functioning.

Methods: In a prospective, observational study, adults with episodic migraine (EM) or chronic migraine (CM) used an eDiary to complete the MPFID (assessing daily impacts of migraine on physical function) and a headache diary (capturing migraine days, migraine pain intensity, and migraine interference) each day, and other PRO instruments related to migraine. Item-level evaluation, item response theory (IRT), and exploratory factor analysis (EFA) methods were applied to identify domains, select final MPFID items, and develop scoring procedures.

Beyond study participants: a framework for engaging patients in the selection or development of clinical outcome assessments for evaluating the benefits of treatment in medical product development.

Background: Patients are participating more actively in health care decision-making with regard to their health, as well as in the broader realm of assessing the value of medical products and influencing decisions about their registration and reimbursement. There is an increasing trend to include patients' perspectives throughout the stages of medical product development by broadening the traditional study-participant role to that of an active partner throughout the process. Including patients in the selection and development of clinical outcome assessments (COAs) to evaluate the benefit of treatment is particularly important.

Measuring the impact of migraine for evaluating outcomes of preventive treatments for migraine headaches.

Background: Migraine is characterized by headache with symptoms such as intense pain, nausea, vomiting, photophobia, and phonophobia that significantly impact individuals' lives. The objective of this study was to develop a strategy to measure outcomes from the patients' perspectives for use in evaluating preventive treatments for migraine.

Methods: This study used a multi-stage process.

The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies.

Background: Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS(™): COPD) scale (formerly EXACT-RS).

Methods: Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction.

Evaluating functional outcomes in adolescents with attention-deficit/hyperactivity disorder: development and initial testing of a self-report instrument.

Background: Engaging adolescents in decisions about their health may enhance their compliance with treatment and result in better health outcomes. Treatment outcomes in attention-deficit/hyperactivity disorder (ADHD) are rarely evaluated from the adolescents' point of view. There is also concern that adolescents with ADHD may not have insight about the impacts of their disease.