Abstract
Background
Parkinson’s Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease ...modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.
Methods/design
DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.
Discussion
DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.
Trial registration
NCT04180865
; registered retrospectively, November 28th 2019.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flexor tendinitis is a common and debilitating injury of elite and recreational athletes. Healing may be improved through intratendinous injection of insulin-like growth factor-I (IGF-I), which has ...been shown in vitro to stimulate mitogenesis and enhance tendon matrix production. This study investigated the effects of intratendinous injection of IGF-I on tendon healing in an equine model of flexor tendinitis. Collagenase-induced lesions were created in the tensile region of the
flexor digitorum superficialis tendon of both forelimbs of eight horses. Treated tendons were injected with 2 μg rhIGF-I intralesionally every other day for 10 injections, while controls received 0.9% NaCl. Tendon fiber deposition and organization were evaluated serially using ultrasonography throughout the 8 week trial period. Following euthanasia, the tendons were harvested and DNA, hydroxyproline, and glycosaminoglycan content determined, mechanical strength and stiffness evaluated, gene expression and spatial arrangement of collagen types I and III assessed by northern blot and in situ hybridization, and tendon fiber architecture assessed by polarized light microscopy. Local soft tissue swelling was reduced in the IGF-I treated limbs. Similarly, lesion size in IGF-I treated tendons was smaller 3 and 4 weeks after initiation of treatment. Cell proliferation and collagen content of the IGF-I treated tendons were increased compared to controls. Mechanically, IGF-I treated tendons showed a trend toward increased stiffness compared to saline treated controls. Considered together with the decreased soft tissue swelling and improved sonographic healing, these data support the potential use of intralesional IGF-I for treatment of debilitating tendon injuries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The acceptability of the combined contraceptive vaginal ring, NuvaRing
®, was assessed during two trials conducted in North America and Europe. Women completed a questionnaire about the ring’s ...clarity of instructions, ease of use, sexual comfort, cycle-related characteristics and satisfaction after 3, 6 and 13 cycles of use. A total of 1950 women (82% of those recruited) completed a questionnaire at cycle 3. At baseline, 66% of participants preferred oral contraceptives, but after three cycles of ring use 81% preferred the ring. On study completion, 97% agreed that the instructions for use were clear; 85% of women and 71% of their partners never/rarely felt the ring during intercourse and 94% of partners never/rarely minded that the woman was using the ring. Overall acceptance was high, 96% were satisfied with the ring and 97% would recommend the ring. Similar responses were seen for women who prematurely discontinued from the studies, except that slightly fewer women were satisfied (60%) and would recommend the ring (75%). Reasons for liking the ring included ‘not having to remember anything’ (45%) and ‘ease of use’ (27%). In conclusion, there is a high level of user and partner acceptability for the contraceptive ring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Randomized trials demonstrated that chromoendoscopy is superior to white light endoscopy with random biopsy sampling (WLE) for the detection of dysplasia in patients with inflammatory bowel disease ...(IBD). Whether implementing chromoendoscopy can increase the detection of dysplasia in clinical practice is unknown.
Patients with ulcerative colitis (UC) and Crohn's disease (CD) undergoing colonoscopic surveillance between January 2000 and November 2013 in three referral centers were identified using the patients' medical records. In recent years, the use of high-definition chromoendoscopy was adopted in all three centers using segmental pancolonic spraying of 0.1% methylene blue or 0.3% indigo carmine (chromoendoscopy group). Previously, surveillance was performed employing WLE with random biopsies every 10 cm (WLE group). The percentage of colonoscopies with dysplasia was compared between both groups.
A total of 440 colonoscopies in 401 patients were performed using chromoendoscopy and 1,802 colonoscopies in 772 patients using WLE. Except for a higher number of CD patients with extensive disease and more patients with a first-degree relative with colorectal cancer (CRC) in the chromoendoscopy group, the known risk factors for IBD-associated CRC were comparable between both groups. Dysplasia was detected during 48 surveillance procedures (11%) in the chromoendoscopy group as compared with 189 procedures (10%) in the WLE group (P=0.80). Targeted biopsies yielded 59 dysplastic lesions in the chromoendoscopy group, comparable to the 211 dysplastic lesions detected in the WLE group (P=0.30).
Despite compelling evidence from randomized trials, implementation of chromoendoscopy for IBD surveillance did not increase dysplasia detection compared with WLE with targeted and random biopsies.
Background
Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived ...disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food‐allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food‐allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL.
Methods
A total of 648 European food‐allergic patients (404 adults, 244 children) completed an age‐specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients.
Results
For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto‐injector (EAI) contributed to impairment of HRQL.
Conclusions
In this study, food allergy‐related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Smoking affects the course of inflammatory bowel disease IBD. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life HrQoL among adults with Crohn's disease ...CD and ulcerative colitis UC.
A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders.
In total, 3030 patients 1558 CD, 1054 UC, 418 IBD-unknown were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 95% confidence interval €6,234 - €9,864 vs €6,017 €5,186 - €6,946 in never-smokers and €5,710 €4,687 - €6,878 in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 95% CI €4,122 - €6,303 vs €9,342 €6,010 - €12,788, p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL.
Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.
Abstract
Gut microbiota alterations in Parkinson’s disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be ...adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (
n
= 136 and 56 PD,
n
= 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.
Background and Aims:
Peripheral joint complaints pJTC and chronic back pain CBP are the most common extra-intestinal manifestations in patients with inflammatory bowel disease IBD. This prospective ...study evaluates variables associated with joint/back pain, including IBD disease activity.
Methods:
IBD patients with back pain ≥ 3 months and/or peripheral joint pain/swelling n = 155, and IBD patients without joint complaints n = 100; controls, were followed for a period of 1 year. Patients were classified as having SpondyloArthritis SpA according to several sets of criteria. Statistical analysis included logistic regression models and linear mixed model analysis.
Results:
Of the 155 patients with joint/back pain, 13 had chronic back pain, 80 peripheral joint complaints, and 62 axial and peripheral joint complaints. Smoking, female gender, and IBD disease activity were independently associated with IBD joint/back pain. The Assessment in Spondyloarthritis International Society criteria for axial and peripheral SpA were fulfilled in 12.3% of patients, with 9.7% n = 15 receiving a rheumatological diagnosis of arthritis. During the 12-month follow-up, the majority of the patients reporting joint/back pain remained stable.
Conclusions:
In our cohort, the majority of IBD patients reported joint/back pain and SpA was relatively common. To facilitate effective care, gastroenterologists should be aware of the various features of SpA to classify joint complaints and, by making use of an efficient referral algorithm, to refer CBP patients to the rheumatologist.
Background and aims:
Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to study the association between smoking and extra-intestinal ...manifestations (EIMs) in inflammatory bowel disease (IBD).
Methods:
We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD.
Results:
In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1–2 years; Groningen cohort, within 1 year).
Conclusions:
There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.
Aim
There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and ...inter‐hospital variation in surgical strategy, and to compare long‐term survival in a propensity score‐matched analysis.
Method
The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver‐limited metastases who underwent liver resection. Survival outcomes of propensity score‐matched groups were compared.
Results
Of 1830 patients, 270 (14.8%) underwent a liver‐first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel‐first approach. The proportion of patients undergoing either a liver‐first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4‐year survival between the propensity score‐matched cohorts according to surgical strategy: bowel first vs simultaneous hazard ratio (HR) 0.92 (95% CI: 0.80–1.06) or bowel first vs liver first HR 0.99 (95% CI: 0.82–1.19).
Conclusion
There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver‐first strategies have comparable long‐term survival to the bowel‐first approach.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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