Population mixing and incidence of cancers in adolescents and young adults between 1990 and 2013 in Yorkshire, UK

Purpose: Epidemiological evidence suggests a role for an infectious etiology for cancers in teenagers and young adults (TYAs). We investigated this by describing associations between infection transmission using the population mixing (PM) proxy and incidence of cancers in TYAs in Yorkshire, UK. Methods: We extracted cancer cases from the Yorkshire Specialist Register of Cancer in Children and Young People from 1990 to 2013 (n = 1929). Using multivariable Poisson regression models (adjusting for effects of deprivation and population density), we investigated whether PM was associated with cancer incidence. We included population mixing–population density interaction terms to examine for differences in effects of PM in urban and rural populations. Results: Nonsignificant IRRs were observed for leukemias (IRR 1.20, 95% CI 0.91–1.59), lymphomas (IRR 1.09, 95% CI 0.90–1.32), central nervous system tumors (IRR 1.06, 95% CI 0.80–1.40) and germ cell tumors (IRR 1.14, 95% CI 0.92–1.41). The association between PM and cancer incidence did not vary in urban and rural areas. Conclusions: Study results suggest PM is not associated with incidence of cancers among TYAs. This effect does not differ between rural and urban settings

Study protocol of the DUtch PARkinson Cohort (DUPARC):a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology

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

Radiation of parotid or submandibular glands is effective for drooling in patients with parkinsonism:a randomised double-blind placebo-controlled trial

BACKGROUND: Drooling is a common symptom in patients with parkinsonism, causing physical and emotional distress. It is unknown which major salivary glands are the best candidates for irradiation to reduce drooling with minimal adverse events. Therefore, this study assessed the efficacy and safety of submandibular and parotid salivary gland irradiation to reduce drooling. METHODS: A prospective, randomised, double-blind, placebo-controlled trial was conducted at the University Medical Center Groningen, the Netherlands. After informed consent, 31 patients with parkinsonism and severe drooling according to the Unified Parkinson Disease Rating Scale (UPDRS) were included in this study. Exclusion criteria consisted of the use of anticholinergic drugs, the existence of salivary gland diseases, and/or an history of (pre)malignancies of the salivary glands. Patients were randomized for parotid-, submandibular- or sham irradiation (2x6 Gy with one week interval). Patients were evaluated at 1, 3, 6 and 12 months after radiation. Primary outcome measure was drooling severity according to the UPDRS. Secondary outcomes measures consisted of stimulated glandular salivary secretion rates and adverse effects. FINDINGS: Overall 31 parkinsonian patients were included. Initially 11 patients were radiated on the parotid glands, 10 patients on the submandibular glands and 10 patients were sham-radiated. After 6 months, the sham-radiated patients were actively treated after a second randomisation. One patient in the parotid radiation group discontinued his participation after three months due to physical deterioration. Radiation of parotid or submandibular glands significantly improved the existing drooling, as compared to placebo radiation. Parotid- and submandibular radiation was equally effective, but more patients in the submandibular radiated group reported sticky saliva vs. patients treated by parotid radiation (33∙33% vs. 13∙33%). INTERPRETATION: Major salivary gland radiation significantly improves drooling in parkinsonian patients with few adverse effects. However, parotid gland radiation is accompanied by fewer side effects and therefore is the preferred mode of radiation in this patient population

Chlamydia control activities in Europe: cross-sectional survey

Background: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. Methods: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. Results: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). Conclusion: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes

Intermuscular coherence as a biomarker of subthalamic nucleus deep brain stimulation efficacy in Parkinson's disease

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD. METHODS: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated. RESULTS: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01). CONCLUSIONS: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement. SIGNIFICANCE: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS

On the relation between virial coefficients and the close-packing of hard disks and hard spheres

The question of whether the known virial coefficients are enough to determine the packing fraction $\eta_\infty$ at which the fluid equation of state of a hard-sphere fluid diverges is addressed. It is found that the information derived from the direct Pad\'e approximants to the compressibility factor constructed with the virial coefficients is inconclusive. An alternative approach is proposed which makes use of the same virial coefficients and of the equation of state in a form where the packing fraction is explicitly given as a function of the pressure. The results of this approach both for hard-disk and hard-sphere fluids, which can straightforwardly accommodate higher virial coefficients when available, lends support to the conjecture that $\eta_\infty$ is equal to the maximum packing fraction corresponding to an ordered crystalline structure.Comment: 10 pages, 6 figures; v2: discussion about hard-square and hard-hexagon systems on a lattice added; five new reference

The detection and modeling of direct effects in latent class analysis

Several approaches have been proposed for latent class modeling with external variables, including one-step, two-step and three-step estimators. However, very little is known yet about the performance of these approaches when direct effects of the external variable to the indicators of latent class membership are present. In the current article, we compare those approaches and investigate the consequences of not modeling these direct effects when present, as well as the power of residual and fir statistics to identify such effects. The results of the simulations show that not modeling direct effect can lead to severe parameter bias, especially with a weak measurement model. Both residual and fit statistics can be used to identify such effects, as long as the number and strength of these effects is low and the measurement model is sufficiently strong

Validity of summing painful joint sites to assess joint-pain comorbidity in hip or knee osteoarthritis

BACKGROUND: Previous studies in patients with hip and knee osteoarthritis (OA) have advocated the relevance of assessing the number of painful joint sites, other than the primary affected joint, in both research and clinical practice. However, it is unclear whether joint-pain comorbidities can simply be summed up. METHODS: A total of 401 patients with hip or knee OA completed questionnaires on demographic variables and joint-pain comorbidities. Rasch analysis was performed to evaluate whether a sum score of joint-pain comorbidities can be calculated. RESULTS: Self-reported joint-pain comorbidities showed a good fit to the Rasch model and were not biased by gender, age, disease duration, BMI, or patient group. As a group, joint-pain comorbidities covered a reasonable range of severity levels, although the sum score had rather low reliability levels suggesting it cannot discriminate well among patients. CONCLUSIONS: Joint-pain comorbidities, in other than the primary affected joints, can be summed into a joint pain comorbidity score. Nevertheless, its use is discouraged for individual decision making purposes since its lacks discriminative power in patients with minimal or extreme joint pain