24 hour-ambulatory blood pressure and heart rate profiles in diagnosing orthostatic hypotension in Parkinson’s disease and Multiple System Atrophy

Background:24-hour ambulatory blood pressure and heart rate monitoring (24hr-ABPM) can provide vital information on circadian blood pressure (BP) profiles, which are commonly abnormal in Parkinson’s disease with and without autonomic failure (PD+AF and PD) and multiple system atrophy (MSA). 24hr-ABPM has not been directly compared between these disorders regarding cardiovascular autonomic function. We aim to determine the usefulness of 24hr-ABPM with diary compared to Head-up Tilting (HUT) in diagnosing orthostatic hypotension (OH) in these patients. Methods: 74 patients (23 MSA,18 PD+AF,33 PD) underwent cardiovascular autonomic screening followed by 24hr-ABPM with diary. Standing tests were included during 24hr-ABPM. The sensitivity and specificity in detecting OH from the 24hr-ABPM standing test were compared with HUT. Results: There was no difference in OH during HUT between MSA and PD+AF (p>0.05). MSA and PD+AF had a higher proportion of abnormal BP circadian rhythms compared to PD (p0.05). Patients were divided into groups with (OH+) and without OH (OH-) on HUT. Using the standing test during 24hr-ABPM, a SBP fall of >20 mmHg showed a sensitivity and specificity of 82% and 100 % (AUC 0.91, 95% CI 0.84-0.98) in differentiating OH+ from OH-, respectively. Conclusions:PD+AF and MSA patients had similar circadian BP patterns suggesting that autonomic dysfunction influences abnormal BP circadian patterns similarly in these disorders. The higher sensitivity and specificity in detecting OH using a SBP fall of >20 mmHg compared to a DBP fall of >10 mmHg during standing test supports its usefulness to assess autonomic function in MSA and PD

Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: results of the COSMOS mixed-methods study

Background:  Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS).  Objective:  To determine the variables that affect continuation or discontinuation of the use of CIC.  Methods:  A three-part mixed-method study (prospective longitudinal cohort (n = 56), longitudinal qualitative interviews (n = 20) and retrospective survey (n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual’s age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity.  Results:  For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation.  Conclusion:  Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person’s readiness to try CIC

On the equivalence of the X-ray scattering retrieval with beam tracking and analyser-based imaging using a synchrotron source

X-ray phase contrast imaging (XPCI) methods give access to contrast mechanisms that are based on the refractive properties of matter on top of the absorption coefficient in conventional x-ray imaging. Ultra small angle x-ray scattering (USAXS) is a phase contrast mechanism that arises due to multiple refraction events caused by physical features of a scale below the physical resolution of the used imaging system. USAXS contrast can therefore give insight into subresolution structural information, which is an ongoing research topic in the vast field of different XPCI techniques. In this study, we quantitatively compare the USAXS signal retrieved by the beam tracking XPCI technique with the gold standard of the analyzer based imaging XPCI technique using a synchrotron x-ray source. We find that, provided certain conditions are met, the two methods measure the same quantity

Multi-modal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy

Objective: To evaluate patients with ganglionic acetylcholine receptor antibody (gAChR‐Ab) positive autoimmune autonomic ganglionopathy using a multi‐modal testing protocol to characterise their full clinical phenotype and explore biomarkers to quantify immunotherapy response. Methods: Cohort study of thirteen individuals (seven female; 21–69 years) with autonomic failure and gAChR‐Ab>100pM identified between 2005–2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and COMPASS‐31 autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head‐up tilt. Eleven patients received immunotherapy. Results: At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7/8 had post‐ganglionic sudomotor dysfunction, 9/11 had urinary retention and xeropthalmia, and 6/8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3[17.8–61.3] to 5.2[1.4–8.2], P = .007), heart rate response to deep breathing (1.5[0.0–3.3] to 4.5[3.0–6.3], P = .02), pupillary constriction to light (12.0[5.5–18.0] to 19.0[10.6–23.8]%, P = .02), saliva production (0.01[0.01–0.05] to 0.08[0.02–0.20]g/min, P = .03) and COMPASS‐31 scores (52 to 17, P = .03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, P = .01) and following immunotherapy (r = 0.889, P = .02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibres supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. Interpretation: Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Background: Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. Methods and Results: EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455650 V vs. CD36- 346653 V, p = 0.001; CD31+436643 V vs. CD31- 340655 V, p = 0.001; MMP-3+ 400668 V vs. MMP-3- 323633 V, p = 0.03)

Detection of distant metastases in patients with oesophageal or gastric cardia cancer: a diagnostic decision analysis

Computed tomography (CT) is presently a standard procedure for the detection of distant metastases in patients with oesophageal or gastric cardia cancer. We aimed to determine the additional diagnostic value of alternative staging investigations. We included 569 oesophageal or gastric cardia cancer patients who had undergone CT neck/thorax/abdomen, ultrasound (US) abdomen, US neck, endoscopic ultrasonography (EUS), and/or chest X-ray for staging. Sensitivity and specificity were first determined at an organ level (results of investigations, i.e., CT, US abdomen, US neck, EUS, and chest X-ray, per organ), and then at a patient level (results for combinations of investigations), considering that the detection of distant metastases is a contraindication to surgery. For this, we compared three strategies for each organ: CT alone, CT plus another investigation if CT was negative for metastases (one-positive scenario), and CT plus another investigation if CT was positive, but requiring that both were positive for a final positive result (two-positive scenario). In addition, costs, life expectancy and quality adjusted life years (QALYs) were compared between different diagnostic strategies. CT showed sensitivities for detecting metastases in celiac lymph nodes, liver and lung of 69, 73, and 90%, respectively, which was higher than the sensitivities of US abdomen (44% for celiac lymph nodes and 65% for liver metastases), EUS (38% for celiac lymph nodes), and chest X-ray (68% for lung metastases). In contrast, US neck showed a higher sensitivity for the detection of malignant supraclavicular lymph nodes than CT (85 vs 28%). At a patient level, sensitivity for detecting distant metastases was 66% and specificity was 95% if only CT was performed. A higher sensitivity (86%) was achieved when US neck was added to CT (one-positive scenario), at the same specificity (95%). This strategy resulted in lower costs compared to CT only, at an almost similar (quality adjusted) life expectancy. Slightly higher specificities (97–99%) were achieved if liver and/or lung metastases found on CT, were confirmed by US abdomen or chest X-ray, respectively (two-positive scenario). These strategies had only slightly higher QALYs, but substantially higher costs. The combination of CT neck/thorax/abdomen and US neck was most cost-effective for the detection of metastases in patients with oesophageal or gastric cardia cancer, whereas the performance of CT only had a lower sensitivity for metastases detection and higher costs. The role of EUS seems limited, which may be due to the low number of M1b celiac lymph nodes detected in this series. It remains to be determined whether the application of positron emission tomography will further increase sensitivities and specificities of metastases detection without jeopardising costs and QALYs

Effect of a Simple Information Booklet on Pain Persistence after an Acute Episode of Low Back Pain: A Non-Randomized Trial in a Primary Care Setting

Mass-media campaigns have been known to modify the outcome of low back pain (LBP). We assessed the impact on outcome of standardized written information on LBP given to patients with acute LBP.A 3-month pragmatic, multicenter controlled trial with geographic stratification.Primary care practice in France.2752 patients with acute LBP.An advice book on LBP (the "back book").The main outcome measure was persistence of LBP three months after baseline evaluation.2337 (85%) patients were assessed at follow-up and 12.4% of participants reported persistent LBP. The absolute risk reduction of reporting persistent back pain in the intervention group was 3.6% lower than in the control group (10.5% vs. 14.1%; 95% confidence interval [-6.3% ; -1.0%]; p value adjusted for cluster effect = 0.01). Patients in the intervention group were more satisfied than those in the control group with the information they received about physical activities, when to consult their physician, and how to prevent a new episode of LBP. However, the number of patients who had taken sick leave was similar, as was the mean sick-leave duration, in both arms, and, among patients with persistent pain at follow-up, the intervention and control groups did not differ in disability or fear-avoidance beliefs.The level of improvement of an information booklet is modest, but the cost and complexity of the intervention is minimal. Therefore, the implications and generalizability of this intervention are substantial.ClinicalTrials.gov NCT00343057