340880 research outputs found
Sort by
Is cardiovascular disease in PCOS driven by MASLD?
No full textRecent genetic studies have implicated an active role for intrahepatic lipid accumulation in the pathogenesis of both polycystic ovary syndrome (PCOS) and cardiovascular disease. These new insights may provide novel (non)pharmacological opportunities for the prevention and treatment of PCOS and cardiovascular disease at both the societal and clinical level
Computational Synaptic Modeling of Pitch and Duration Mismatch Negativity in First-Episode Psychosis Reveals Selective Dysfunction of the N-Methyl-D-Aspartate Receptor
No full textMismatch negativity (MMN) to pitch (pMMN) and to duration (dMMN) deviant stimuli is significantly more attenuated in long-term psychotic illness compared to first-episode psychosis (FEP). It was recently shown that source-modeling of magnetically recorded MMN increases the detection of left auditory cortex MMN deficits in FEP, and that computational circuit modeling of electrically recorded MMN also reveals left-hemisphere auditory cortex abnormalities. Computational modeling using dynamic causal modeling (DCM) can also be used to infer synaptic activity from EEG-based scalp recordings. We measured pMMN and dMMN with EEG from 26 FEP and 26 matched healthy controls (HCs) and used a DCM conductance-based neural mass model including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, N-methyl-D-Aspartate (NMDA), and Gamma-aminobutyric acid receptors to identify any changes in effective connectivity and receptor rate constants in FEP. We modeled MMN sources in bilateral A1, superior temporal gyrus, and inferior frontal gyrus (IFG). No model parameters distinguished groups for pMMN. For dMMN, reduced NMDA receptor activity in right IFG in FEP was detected. This finding is in line with literature of prefrontal NMDA receptor hypofunction in chronic schizophrenia and suggests impaired NMDA-induced synaptic plasticity may be present at psychosis onset where scalp dMMN is only moderately reduced. To the best of our knowledge, this is the first report of impaired NMDA receptor activity in FEP found through computational modeling of dMMN and shows the potential of DCM to non-invasively reveal synaptic-level abnormalities that underly subtle functional auditory processing deficits in early psychosis.</p
A 5-year natural history cohort of patients with facioscapulohumeral muscular dystrophy determining disease progression and feasibility of clinical outcome assessments for clinical trials
No full textIntroduction/AimsThe number of clinical trials in facioscapulohumeral muscular dystrophy (FSHD) is expected to increase in the near future. There is a need for clinical outcome assessments (COAs) that can capture disease progression over the relatively short time span of a clinical trial. In this study, we report the natural progression of FSHD and determine the feasibility of COAs for clinical trials.MethodsGenetically confirmed FSHD patients underwent various COAs at baseline and after 5 years. COAs consisted of the Motor Function Measure (MFM), manual muscle testing using the Medical Research Council score, six-minute walk test, quantitative muscle strength assessment of the quadriceps muscle, clinical severity score, and FSHD evaluation score (FES). Statistical significance and the minimal clinically important difference (MCID) were calculated and power calculations were performed.ResultsOne hundred fifty-four symptomatic FSHD patients were included, with a mean (SD) age of 51.4 (14.6) years old. All COAs showed a minimal, yet statistically significant progression after 5 years. MCID was reached for the MFM Domain 1, MFM total score, and FES. These three COAs showed the lowest sample size requirements for clinical trials (185, 156, and 201 participants per group, respectively, for a trial duration of 2 years).DiscussionThe captured FSHD disease progression rate in 5 years was generally minimal. The COAs in this study are not feasible for clinical trials with a duration of 2 years. Extended trial durations or novel outcome assessments might be necessary to improve trial feasibility in FSHD
Primary percutaneous metal stenting above the ampulla in resectable perihilar cholangiocarcinoma
No full textIntroductionWe present a case of a patient with resectable perihilar cholangiocarcinoma (pCCA) who underwent primary metal stenting above the ampulla, followed by a successful surgical resection. Biliary drainage is a crucial step in the preoperative management of pCCA, yet there is no consensus on the optimal approach. Traditional drainage methods involve passing through the ampulla and/or the skin barrier, thereby increasing the risk of bacterial contamination of the biliary tree and secondary cholangitis.MethodA novel drainage technique was utilised in this case. A metal stent was percutaneously placed across the malignant hilar stenosis without external biliary drainage. During the procedure, both guidewires and stents were meticulously prevented from passing through the ampulla. Additionally, percutaneous access to the biliary tree was removed during the index procedure to minimise the risk of biliary colonisation and cholangitis.ResultsFollowing the drainage, bilirubin levels rapidly normalised, and no clinical or biochemical signs of cholangitis were observed. This allowed for rapid and uncomplicated surgical resection.ConclusionThis case illustrates the potential of a novel biliary drainage technique in patients with pCCA. By minimising the risk of biliary colonisation and cholangitis, this approach could potentially improve surgical outcomes
The impact of affective and negative symptoms on the development of psychosis in a six-year follow-up of a community-based population
No full textPurposeThe Clinical High Risk (CHR) concept has a limited transition risk to psychotic disorders (PD). This study investigates the association between affective and negative symptoms, currently not included in the CHR concept, and the risk of transition to PD in a community-based population of 2185 participants in Turkey.MethodsParticipants were assessed twice over six years using a multistage sampling technique. Two separate linear regression analyses were conducted on data from both assessments, investigating the relationship between affective and negative symptoms, subclinical and clinical psychotic experiences (PE) and progression to PD.ResultsThe overall transition rate to PD was 1.3%. The analysis showed no increased risk of developing PD for the 'subclinical PE only' group at follow-up, compared to the 'no PE' group. However, being classified as having 'clinical PE only' (OR: 6.23; p = 0.010) and 'clinical PE + affective/negative symptoms' (OR: 8.48; p = 0.001) at baseline was associated with an increased risk of developing PD at follow-up. The presence of 'affective/negative symptoms' at baseline was associated with an increased risk of incident subclinical PE (RR: 1.98; p = 0.001), incident clinical PE (RR: 3.14; p = 0.001), and incident PD (RR: 4.21; p = 0.030) at follow-up.ConclusionThe results confirm the significance of the baseline severity of positive symptoms in predicting the transition to PD and suggest that both positive and affective/negative symptoms impact the transition risk to PD and incident psychotic symptoms. This highlights the potential utility of defining CHR groups based on a combination of positive, affective, and negative symptoms
The impact of different radiology report formats on patient information processing:a systematic review
No full textBackground: Since radiology reports are primarily written for health professionals, patients may experience difficulties understanding jargon and terminology used, leading to anxiety and confusion. Objectives: This review evaluates the impact of different radiology report formats on outcomes related to patient information processing, including perception, decision (behavioral intention), action (actual health behavior), and memory (recall of information). Methods: PubMed, Web of Science, EMBASE, and PsycInfo were searched for relevant qualitative and quantitative articles describing or comparing ways of presenting diagnostic radiology reports to patients. Two reviewers independently screened for relevant articles and extracted data from those included. The quality of articles was assessed using the Mixed Methods Appraisal Tool. Results: Eighteen studies, two qualitative and sixteen quantitative, were included. Sixteen studies compared multiple presentation formats, most frequently traditional unmodified reports (n = 15), or reports with anatomic illustrations (n = 8), lay summaries (n = 6) or glossaries (n = 6). Glossaries, illustrations, lay summaries, lay reports or lay conclusions all significantly improved participants’ cognitive perception and perception of communication of radiology reports, compared to traditional reports. Furthermore, these formats increased affective perception (e.g., reduced anxiety and worry), although only significant for lay reports and conclusions. Conclusion: Modifying traditional radiology reports with glossaries, illustrations or lay language enhances patient information processing. Key Points: Question Identifying the impact of different radiology report formats on outcomes related to patient information processing to enhance patient engagement through online access to radiology reports. Findings Lay language summaries, glossaries with patient-oriented definitions, and anatomic illustrations increase patients’ satisfaction with and understanding of their radiology reports. Clinical relevance To increase patients’ satisfaction, perceived usefulness and understanding with radiology reports, the use of lay language summaries, glossaries with patient-oriented definitions, and anatomic illustrations is recommended. These modifications decrease patients’ unnecessary insecurity, confusion, anxiety and physician consultations after viewing reports.</p
Role of the GH-IGF Axis in Statural Growth and Harmonious Body Proportionality:In Search of Vitruvian Man
No full textContext Body proportions are the objective parameters of harmonious growth and reflect the interplay of genetic, environmental, metabolic, and hormonal actions. Mutations in the growth hormone receptor gene (GHR) result in severe growth failure. The study of individuals affected with these mutations can inform us about the role of growth peptides in harmonious, proportional growth. Objective The aim of this study was to critically assess the role of the growth hormone-insulin-like growth factor (GH-IGF) axis in statural growth and in particular body proportionality. Methods In this epidemiological, noninterventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adults with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of GHR, to their carrier and noncarrier relatives, and to noncarrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations. Results In this cohort of 201 adults, sex-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), and hand and foot length were lower in the GHI individuals than in the other groups. The GHI individuals had the lowest lower segment/Ht, the highest upper segment/Ht, the lowest arm span/Ht and the highest HC/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentrations displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the HC/Ht ratio. Conclusion These findings indicate that individuals homozygous for the GHR mutation have disharmonious body proportions due to abnormal GH/IGF-I action on the growth of the long bones. Contrary to common assumptions, disruption of the GH-IGF axis results in disproportionality and disharmonious growth.</p
Long-Term Outcomes of Early Surgery vs Endoscopy First in Chronic Pancreatitis:Follow-Up Analysis of the ESCAPE Randomized Clinical Trial
No full textIMPORTANCE: Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach. OBJECTIVE: To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: Between April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023. EXPOSURE: Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach. MAIN OUTCOMES AND MEASURES: The primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle. RESULTS: In this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were "very satisfied" with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]). CONCLUSIONS AND RELEVANCE: In this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes
Measuring energy expenditure in narcolepsy using doubly labeled water and respiration chamber calorimetry
No full textSTUDY OBJECTIVES: Hypocretin deficiency causes type 1 narcolepsy, a condition characterized by excessive daytime sleepiness, cataplexy, and fragmented nocturnal sleep. Two-thirds of people with narcolepsy are also overweight, of which half are obese. The pathophysiology behind weight gain in people with narcolepsy remains unknown. We assessed a possible decrease in energy expenditure as a cause for overweight in narcolepsy using respiration chamber calorimetry and doubly labeled water. METHODS: Ten males with type I narcolepsy and nine matched (for age, sex, and BMI) healthy controls were enrolled. Participants stayed in a respiration chamber for 24 hours. They subsequently received doubly labeled water and wore an accelerometer for 2 weeks to assess energy expenditure and physical activity under daily living conditions. Total daily energy expenditure, resting energy expenditure (REE), overnight metabolic rate, physical activity level, and activity-induced energy expenditure were measured. RESULTS: No significant differences were found in REE, mean 24-hour respiration chamber energy expenditure, overnight metabolic rate, and activity-induced energy expenditure when comparing people with narcolepsy type 1 to controls. Physical activity was also comparable between groups. CONCLUSIONS: Energy expenditure in narcolepsy type 1 is similar to matched controls, suggesting comparable metabolism and physical activity rates. It remains possible that metabolic changes are most pronounced around disease onset. In addition, patients had to discontinue their medication which may have influenced the results. Still, our findings suggest that other factors may also play a role in weight gain in narcolepsy, such as differences in dietary behavior.</p
