Patient Perspective on Acute Intermittent Porphyria with Frequent Attacks: A Disease with Intermittent and Chronic Manifestations.

OBJECTIVE: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living. METHODS: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences. RESULTS: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms. CONCLUSIONS: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.

Greater BOLD response to working memory in endurance-trained adults revealed by breath-hold calibration.

BACKGROUND: Cardiorespiratory fitness is associated with increased frontal and parietal activation during executive function tasks. While these findings suggest fitness-related enhancement of neuronal response, the utility of functional magnetic resonance imaging (fMRI) may be limited by potential fitness-related differences in global vascular reactivity. The aim of this study was to determine if highly fit adults display differential activation during working memory after calibration for vascular reactivity relative to their sedentary counterparts. METHODS: Thirty-two endurance-trained and 24 sedentary adults, aged 40-65 years, completed a 2-Back verbal working memory task and a breath-hold challenge during fMRI. Group differences in blood oxygen level-dependent (BOLD) response during working memory were examined across the whole brain and in a priori regions of interest (ROI) before and after breath-hold calibration using non-parametric permutation testing. Multiple regression was used to explore the association between cardiorespiratory fitness (VO2 max), age, and calibrated 2-Back-related activation within the one a priori ROI with significant group effects. RESULTS: In comparison to the endurance-trained group, the sedentary group exhibited greater BOLD signal changes in response to the breath-hold task. After, but not before calibration, the endurance-trained group displayed significantly higher 2-Back-related activation in the right middle frontal gyrus (P = 0.049). Older age predicted lower 2-Back-related activation (ß = -0.308, P = 0.031), whereas fitness predicted higher activation (ß = 0.372, P = 0.021) in this region. CONCLUSIONS: Breath-hold calibration increased detection of working memory-related BOLD response differences between sedentary and endurance-trained adults. Moreover, cardiorespiratory fitness appeared to mitigate age-related changes in BOLD during working memory in this region.