Symptom burden of people with progressive ataxia, and its wider impact on their friends and relatives: a cross-sectional study

Background: Progressive ataxias are complex disorders that result in a wide variety of symptoms. Whilst we currently have a relatively good understanding of the symptom patterns associated with the various types of ataxia, and how these diseases progress over time, their impact on the person with ataxia is less well understood. In addition, little is known about how carers, friends and families are affected by them. This paper aims to provide preliminary information on the presence and impact of medical symptoms and day-to-day challenges on people with ataxia and their friends and relatives. Method: Data were extracted from a survey by Ataxia UK for their members. The views of 366 people with ataxia and 52 friends and relatives are reported. Data were analysed for the entire groups, as well as for the three most common ataxia types represented in the sample, Friedreich’s ataxia, inherited ataxia (excluding Friedreich’s ataxia), and cerebellar ataxia of unknown cause. Results: The survey confirmed the symptom patterns described in previous research, but further showed that the impact of these symptoms can vary across ataxia populations. Similar findings were observed for day-to-day challenges. Friends and relatives experienced similar challenges to people with ataxia, indicating that support provided has to consider those supporting people with ataxia as well as the patient. Respondents also highlighted limitations in terms of accessing support services, and not all services were able to cater fully to their specific needs. Conclusion: This study begins to provide information that can be used in further research to explore the needs of people with ataxia and their carers, friends, and relatives. Such research will support treatment trial design, ensuring patients’ needs are considered, help to tailor support services to their needs, and ensure health care professionals have the necessary skills to fully address them.

Different clinical symptom patterns in patients with reflux micro-micro-aspiration

BackgroundPulmonary manifestation of gastro-oesophageal reflux disease (GORD) is a well-recognised entity, however little primary reported data exists on presenting symptoms of patients in whom reflux micro-aspiration is confirmed. The aim of this study is to report symptoms and presenting patterns of a large group of patients with confirmed reflux micro-aspiration.Patients and methodsData was extracted from a prospectively populated database of patients referred to a tertiary specialist centre with severe, refractory, or atypical reflux. Patients with reflux micro-aspiration on scintigraphy were included in this study. Separate group included patients with evidence of proximal reflux to the level of pharynx when supine and/or upright.ResultsInclusion criteria were met by 243 patients with confirmed reflux micro-aspiration (33% males; mean age 59). Most common symptoms amongst patients with micro-aspiration were regurgitation (72%), cough (67%), heartburn (66%), throat clearing (65%), and dysphonia (53%). The most common two-symptom combinations were heartburn/regurgitation, cough/throat clearing, regurgitation/throat clearing, cough/regurgitation and dysphonia/throat clearing. The most common three-symptom combinations were cough/heartburn/regurgitation, cough/regurgitation/throat clearing and dysphonia/regurgitation/throat clearing. Cluster analysis demonstrated two main symptom groupings, one suggestive of proximal volume reflux symptoms and the other with motility/inflammatory bowel syndrome (IBS)-like symptoms (bloat, constipation).ConclusionCombination of typical symptoms of GORD such as heartburn or regurgitation and a respiratory or upper aero-digestive complaint such as cough, throat clearing, or voice change should prompt consideration of reflux micro-aspiration.

SENSIBLE DIAGNOSES FOR SENSIBLE CLINICIANS: THE NEW EDITION OF THE PSYCHODYNAMIC DIAGNOSTIC MANUAL (PDM-2)

The article analyzes psychodynamic clinical models focused on clinical case formulation and treatment planning, offers practitioners empirically grounded and clinically validated alternatives to such personality maps as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). The PDM-2 diagnostic model aims to provide a systematic description of healthy functioning and personality disorders; individual profiles of mental functioning (including patterns of relationships with other people, understanding and expressing feelings, overcoming stress and anxiety, regulating impulses, observing one's own emotions and behavior and forming moral judgments, etc.); as well as symptom patterns, including differences in each person's subjective experience of symptoms and in the subjective experiences of treating therapists.

Exploration of Parkinson’s Disease Symptomatology Subtypes From the Caregiver Perspective: Implications for Caregiver Burden, Depression, and Anxiety

Background: While research has demonstrated associations between Parkinson’s disease (PD) severity and caregiver burden and emotional functioning, less is known about the associations between specific PD symptom patterns and caregiver functioning. Objective: The purpose of the current study was to explore symptomatology subtypes in PD from the caregiver perspective in the U.S. and Mexico and to determine whether caregiver burden, depression, or anxiety differed by PD symptomatology subtype. Methods: Two hundred fifty-three caregivers ( M age = 59.9) completed Parts I and II of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Zarit Burden Interview, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scales. Results: Cluster analysis using domains from the MDS-UPDRS revealed 5 symptomatology subtypes: pain/motor predominant, low symptoms, severe diffuse symptoms, moderate restricted symptoms with speech/oral predominant, and mood predominant. Caregiver burden was greatest for caregivers of individuals in the severe diffuse symptom and moderate restricted symptoms with speech/oral predominant clusters. High caregiver depression and caregiver anxiety were observed in all clusters other than the low symptoms cluster. There were no site by cluster interactions, suggesting that symptom patterns contribute to caregiver functioning in similar ways in the U.S. and Mexico. Conclusions: This data-driven analysis revealed 5 symptomatology subtypes of PD from caregivers’ perspectives and highlighted the need for treatments and interventions based on predominant PD symptom expression. Importance of caregiver support across various symptomatology expressions, and particularly on specialist treatment for predominant speech/oral difficulties was recommended.

Concordance of Skin Prick Test, Intradermal Testing, Serum IgE Levels and Symptoms in Patients with Allergic Rhinitis

Background: Diagnosis of allergic rhinitis is achieved by a combination of patient history and different screening tools, followed by specific provocation testing. Screening tools usually involve a skin prick test (SPT), specific serum IgE or a combination of both. Objective: The purpose of this study was to evaluate the correlation of SPT, intradermal testing and specific serum IgE testing in certain allergens and to evaluate sensitization rates, symptom patterns and time of symptoms in a cohort of patients with suspected allergic rhinitis. Methods: Data on 4653 patients with suspected allergic rhinitis were included and divided into five groups: spring bloomers (birch, hazel, etc.), summer bloomers (grasses and rye), autumn bloomers (ribwort and mugwort), mites and mold. Correlation of SPT, intradermal testing and specific IgE test results using Cohen’s kappa and logistic regression were carried out to evaluate the probability of symptoms. Results: Comparison of SPT and specific serum IgE led to kappa coefficients between 0.33 and 0.47, corresponding to a minor to moderate concordance. Comparing the symptoms reported by patients with sensitization diagnosed by SPT, a correlation was only found for spring and summer bloomers with an odds ratio of 1.5 and 2.1, respectively. The most prevalent symptom in the study cohort was rhinitis, followed by others such as asthma, sense of smell and atopic dermatitis. Conclusions: SPT seems to be more sensitive than specific IgE for detection of sensitization. Patients’ symptoms as well as the timing of symptoms, especially for perennial allergies, are not always very pronounced.

Rheum to Diagnosis: A Mixed Methods Study to Uncover Impediments to Accurate Diagnosis of Nonradiographic Axial Spondyloarthritis in the United States

BackgroundDelayed diagnosis of axial spondyloarthritis (axSpA) is well documented, but little is known about the distinct diagnostic journey and impediments for US patients with nonradiographic axSpA (nr-axSpA).MethodsInterviews of adults with rheumatologist-diagnosed nr-axSpA and of rheumatologists explored the diagnostic journey and barriers to diagnosis. Emerging themes were further explored in an online patient survey. Patients were recruited through Spondylitis Association of America outreach and patient panels. ResultsInterviews were conducted with 25 patients (mean age, 45 years; 80% female) and 16 rheumatologists. Survey responses from 186 eligible patients (median age, 40 years; 67% female) were analyzed. Among surveyed patients, median time from symptom onset to nr-axSpA was 3.25 years. In multivariable analysis, delayed diagnosis was significantly more likely for women and people in rural areas. Most patients consulted ≥4 different types of healthcare providers (HCPs) before seeing a rheumatologist and consulted ≥2 rheumatologists before nr-axSpA diagnosis. Identified impediments to timely diagnosis included the insidious onset of bothersome but tolerable chronic pain; episodic rather than persistent symptom patterns that seemed related to activity; symptoms other than chronic lumbosacral back pain that were dominant and required medical consultation; and widespread unfamiliarity with and misperceptions about nr-axSpA among frontline HCPs, radiologists, and rheumatologists. ConclusionsDelayed nr-axSpA diagnosis is common and reflects HCP knowledge gaps as well as frequent patient presentation with dominant nonaxial symptoms. Targeted HCP education, further research into early disease patterns, and interventions sensitive to the broader spectrum of nr-axSpA manifestations are needed to improve timely diagnosis. Trial RegistrationNot applicable.

641 CLINICAL SYMPTOM PATTERNS IN PATIENTS WITH REFLUX ASPIRATION

Multiple papers have discussed pulmonary manifestation of gastro-oesophageal reflux disease (GORD), however little primary reported data exists on presenting symptoms of patients in whom reflux aspiration is confirmed. The aim of this study is to report symptoms and presenting patterns of a large group of patients with confirmed reflux aspiration. Methods Data was extracted from a prospectively populated database of patients referred to a tertiary specialist centre with severe, refractory, or atypical reflux. Patients with reflux aspiration on scintigraphy were included in this study. Separate group included patients with evidence of proximal reflux to the level of pharynx when supine and/or upright. Results Inclusion criteria were met by 243 patients (33% males; mean age 59). Most common symptoms amongst patients with aspiration were regurgitation (72%), cough (67%), heartburn (66%), throat clearing (65%), and dysphonia (53%). The most common two-symptom combinations were heartburn/regurgitation, cough/throat clearing, regurgitation/throat clearing, cough/regurgitation and dysphonia/throat clearing. The most common three-symptom combinations were cough/heartburn/regurgitation, cough/regurgitation/throat clearing and dysphonia/regurgitation/throat clearing. Clusters analysis demonstrated two main symptom clusters one suggestive of proximal large volume reflux symptoms (regurgitation, heartburn) and the other with IBS type symptoms (bloat, dysphagia, constipation). Conclusion Combination of typical symptoms of GORD and a respiratory or upper aero-digestive complaint should prompt consideration of reflux aspiration. Cluster analysis of symptoms in this group supports previously postulated hypothesis of reflux aspiration pathogenesis by either large volume proximal reflux or by ineffective oesophageal motility.

Heterogeneity in Symptoms in Depression - A replication study in a Digital Mental Health Intervention using the PHQ-9 Questionnaire (Preprint)

BACKGROUND Past work has shown massive variation in depressive symptoms between patients, challenging the perception of major depressive disorder (MDD) as being uniform. This appears quite relevant also for digital mental health (DMH) interventions. While individualization is one of the key potentials of these approaches, this is regularly not utilized and the same static depression treatment is offered to all patients. OBJECTIVE This paper aims to replicate the approach from Fried & Nesse (2015), analyzing the variation of depressive symptoms within 1757 participants in a DMH intervention for depression and anxiety. METHODS Participants’ answers to the single items of the Patient Health Questionnaire 9-item scale (PHQ-9) were used to identify distinct patterns out of the 9 core symptoms of the DSM-5. RESULTS Overall, the 1757 participants showed 231 different patterns of symptoms. The most regular pattern occurred for 8% of the patients. 85% of the participants had a symptom pattern that was shared with less than 4% of the whole sample. The number of unique symptom patterns per participant decreased with higher symptom severity, but the 342 patients with overall severe depression symptoms still exhibited 34 different constellations of single symptoms. CONCLUSIONS The large variation in symptoms challenges the assignment of static depression interventions in DMH and calls for more individualized treatment procedures. Luckily, such procedures can be implemented particularly easily in an app-based context, for example by modular program structures.

Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing

Major depressive disorder (MDD) is the single largest contributor to global disability and up to 20–30% of patients do not respond to at least two antidepressants (treatment-resistant depression, TRD). This study leveraged imputed gene expression in TRD to perform a drug repurposing analysis. Among those with MDD, we defined TRD as having at least two antidepressant switches according to primary care records in UK Biobank (UKB). We performed a transcriptome-wide association study (TWAS) of TRD (n = 2165) vs healthy controls (n = 11,188) using FUSION and gene expression levels from 21 tissues. We identified compounds with opposite gene expression signatures (ConnectivityMap data) compared to our TWAS results using the Kolmogorov-Smirnov test, Spearman and Pearson correlation. As symptom patterns are routinely assessed in clinical practice and could be used to provide targeted treatments, we identified MDD subtypes associated with TRD in UKB and analysed them using the same pipeline described for TRD. Anxious MDD (n = 14,954) and MDD with weight gain (n = 4697) were associated with TRD. In the TWAS, two genes were significantly dysregulated (TMEM106B and ATP2A1 for anxious and weight gain MDD, respectively). A muscarinic receptor antagonist was identified as top candidate for repurposing in TRD; inhibition of heat shock protein 90 was the main mechanism of action identified for anxious MDD, while modulators of metabolism such as troglitazone showed promising results for MDD with weight gain. This was the first TWAS of TRD and associated MDD subtypes. Our results shed light on possible pharmacological approaches in individuals with difficult-to-treat depression.