Ensuring Stakeholder Feedback in the Design and Conduct of Clinical Trials for Rare Diseases: ISCTM Position Paper of the Orphan Disease Working Group.

The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor.

"The ignored pain" - experiences of encounters with healthcare from the perspective of women with pain persisting after childbirth - a qualitative study.

Introduction: Although the prevalence of pain persisting after pregnancy or labour decreases with time, up to 35 % of women report pain 8 months to 12 years after childbirth. To prevent the development and reduce the impact of chronic pain, researchers and clinicians emphasize the importance of early diagnosis as well as timely and appropriate treatment. Previous studies have shown that when women with post-childbirth morbidities consult healthcare professionals during the first year following birth, their problems are often neglected, and they do not receive adequate treatment.

Disempowering women-a mixed methods study exploring informational support about pain persisting after childbirth and its consequences.

Background: Access to information is essential to achieving individual empowerment; meaning the ability to exercise control, manage one's own condition and make informed decisions. However, studies have shown that information provided to women regarding physiological changes during the postpartum period and postpartum health was inadequate, incorrect, or inconsistent.

Methods: The aim of this study was to explore informational support about pain persisting after childbirth and its consequences.

Disease Progression in Multiple System Atrophy-Novel Modeling Framework and Predictive Factors.

Background: Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course.

Objectives: The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease.

Sensitivity to Change and Patient-Centricity of the Unified Multiple System Atrophy Rating Scale Items: A Data-Driven Analysis.

Background: The Unified Multiple System Atrophy Rating Scale (UMSARS) is a commonly used semiquantitative rating scale to assess symptoms and measure disease progression in multiple system atrophy (MSA). However, it is currently incompletely understood which UMSARS items are the most sensitive to change and most relevant to the patient.

Objective: The objective of this study was to assess sensitivity to change and patient-centricity of single UMSARS items.

Clinician- and Patient-reported Endpoints in CNS Orphan Drug Clinical Trials: ISCTM Position Paper on Best Practices for Endpoint Selection, Validation, Training, and Standardization.

Objective: The International Society of CNS Clinical Trials Methodology (ISCTM) Working Group on Rare Disease/Orphan Drug Development is dedicated to improving and streamlining trials to best develop new treatments for rare diseases. The rarity of these disorders requires a drug development strategy that differs from those of nonrare conditions. Rare disease drug development programs are challenged with small sample sizes, heterogeneous clinical presentations, and few, if any, off-the-shelf endpoints.

Grieving over the past and struggling forward - a qualitative study of women's experiences of chronic pain one year after childbirth.

Objective: To describe women's experiences of chronic pain related to childbirth approximately one year after labour.

Design: A qualitative design with face-to-face interviews analysed using inductive qualitative content analysis.

Participants: Twenty women who reported chronic pain, with onset during pregnancy and/or following labour, approximately one year after childbirth.

Building clinically relevant outcomes across the Alzheimer's disease spectrum.

Demonstrating that treatments are clinically meaningful across the Alzheimer's disease (AD) continuum is critical for meeting our goals of accelerating a cure by 2025. While this topic has been a focus of several Alzheimer's Association Research Roundtable (AARR) meetings, there remains no consensus as to what constitutes a "clinically meaningful outcome" in the eyes of patients, clinicians, care partners, policymakers, payers, and regulatory bodies. Furthermore, the field has not come to agreement as to what constitutes a clinically meaningful treatment effect at each stage of disease severity.

Simultaneous modeling of Alzheimer's disease progression via multiple cognitive scales.

Analyzing the progression of Alzheimer's disease (AD) is challenging due to lacking sensitivity in currently available measures. AD stages are typically defined based on cognitive cut-offs, but this results in heterogeneous patient groups. More accurate modeling of the continuous progression of the disease would enable more accurate patient prognosis.

Raising awareness about chronic pain and dyspareunia among women - a Swedish survey 8 months after childbirth.

Background and aims Although several studies have been conducted, knowledge about chronic pain and dyspareunia after childbirth is still limited. The aim of this study was to explore the prevalence of chronic pain 8 months after childbirth in a cohort of Swedish women. The characteristics of chronic pain, such as, pain intensity, localization and frequency as well as pain interference with daily activities were examined.

Differential effects of depressive symptoms on prospective and retrospective memory in old age.

The effects of depressive symptoms on prospective and retrospective memory were examined in a population-based sample of elderly persons (n = 404). Depression was assessed using the Comprehensive Psychopathological Rating Scale and treated as a continuous variable. The variation in depressive symptoms ranged from no symptoms to presence of a clinical depression.

Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis.

To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (< 75 years) and shorter follow-up intervals (< 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory.

Alzheimer's disease and depression: preclinical comorbidity effects on cognitive functioning.

Both Alzheimer's disease (AD) and depression (D) are prevalent disorders in old age and may co-occur in the same individual. The present study examined whether a diagnosis of D in AD has negative effects on cognitive functioning in the preclinical stage of the diseases, as well as at the time when the diagnoses were rendered. Population-based samples of 13 individuals with incident AD and D, 109 incident AD cases without D, and 179 normal older adults were followed over a three-year period.

Negligible effects of depression on verbal and spatial performance in Alzheimer's disease.

We examined whether a diagnosis of depression affects verbal and visuospatial performance in Alzheimer's disease (AD). Using data from a population-based study, persons with AD and depression (AD/D), AD alone and a control group of normal older adults were compared in two tests of verbal ability (category and letter fluency) and two tests of visuospatial skill (block design and clock drawing). As expected, there were clear AD-related deficits across all cognitive tasks.