The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma

Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. In particular, very few osteosarcoma metastases have been sequenced to date, critical to better understand mechanisms of progression and evolution in this tumor. We performed an integrated whole genome and exome sequencing analysis of paired primary and metastatic pediatric osteosarcoma specimens to identify recurrent genomic alterations. Sequencing of 13 osteosarcoma patients including 13 primary, 10 metastatic, and 3 locally recurring tumors revealed a highly heterogeneous mutational landscape, including cases of hypermutation and microsatellite instability positivity, but with virtually no recurrent alterations except for mutations involving the tumor suppressor genes RB1 and TP53. At the germline level, we detected alterations in multiple cancer related genes in the majority of the cohort, including those potentially disrupting DNA damage response pathways. Metastases retained only a minimal number of short variants from their corresponding primary tumors, while copy number alterations showed higher conservation. One recurrently amplified gene, KDR, was highly expressed in advanced cases and associated with poor prognosis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Student learning outcomes,perceptions and beliefs in the context of strengthening research integration into the first year of medical school

Research integrated into undergraduate education is important in order for medical students to understand and value research for later clinical practice. Therefore, attempts are being made to strengthen the integration of research into teaching from the first year onwards. First-year students may interpret attempts made to strengthen research integration differently than intended by teachers. This might be explained by student beliefs about learning and research as well as student perceptions of the learning environment. In general, student perceptions of the learning environment play a pivotal role in fostering student learning outcomes. This study aims to determine whether a curriculum change intended to promote research integration fosters student learning outcomes and student perceptions of research integrated into teaching. To serve this purpose, three subsequent cohorts of first-year students were compared, one before and two after a curriculum change. Learning outcomes of these students were measured using scores on a national progress test of 921 students and assessments of a sample of 100 research reports of a first-year student research project. 746 Students filled out the Student Perceptions of Research Integration Questionnaire. The findings suggest that learning outcomes of these students, that is, scores on research related test items of the progress test and the quality of research reports, were better than those of students before the curriculum change.     

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter-and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the perinuclear space and Golgi compartment. The function of these proteins is currently under investigation.     

Aetiological factors for oral manifestations of HIV

OBJECTIVES: Describe the oral diseases in HIV-infected individuals in London, UK and identify social and medical factors related to the presence of specific oral diseases.
DESIGN: Cross-sectional analytic study.
SETTING: Dental clinics.
SUBJECTS: Consecutive sample of 456 patients with HIV infection.
METHODS: Social and medical history and clinical examinations. Univariate and logistic regression analysis.
OUTCOMES: Presence of HIV-associated oral disease.
RESULTS: 80% of patients with AIDS and 50% of patients with HIV had a specific oral disease. The most common diseases were hairy leukoplakia (30%), erythematous candidiasis (24%), pseudomembranous candidiasis (14%), angular chielitis (6%), necrotising periodontal disease (8%) and non-recurrent ulceration (6%).
CONCLUSIONS: The presence of erythematous candidiasis was not related to advanced HIV disease. Pseudomembranous candidiasis, hairy leukoplakia and mucosal ulceration were significantly associated with advanced HIV disease. Smoking was also identified as a strong aetiological factor in oral diseases. Longitudinal studies are required to further explore the prognostic significance of oral diseases in HIV infection.     

Clinical evaluation of brushing time and plaque removal potential of two manual toothbrushes

Abstract: Aim: To compare plaque removal efficacy of Oral‐B CrossAction (CA) used for 1 min with an American Dental Association (ADA) manual toothbrush used for 2 or 5 min in an examiner‐blind, three‐treatment, six‐period crossover study. Materials and methods: After refraining from all oral hygiene procedures for 23–25 h, subjects were randomly assigned to one of nine possible six‐period (visit) treatment sequences. Plaque was assessed at baseline (Rustogi Modified Navy Plaque Index). Post‐brushing scores were recorded after brushing with a marketed dentifrice and the assigned toothbrush for the specified duration. The same procedure was followed at each of six subsequent visits. Clinical measurements were carried out by the same examiner. Results: Forty subjects completed the study. All three treatments effectively removed plaque from the whole mouth, along the gingival margin and from approximal surfaces. Whole mouth and gingival margin plaque removal scores with CA for 1 min did not differ significantly from scores with the ADA toothbrush used for 2 min. The ADA brush used for 5 min showed significantly greater whole mouth (P < 0.001) and gingival margin (P < 0.001) plaque reduction than the two other treatments. Approximal plaque removal scores did not differ between the three treatments. Conclusions: Efficient plaque removal can be achieved after 1 min of brushing with CA. The amount of plaque removed did not differ significantly from that achieved with the ADA brush after 2 min of brushing. Greater whole mouth and gingival margin plaque removal scores were seen with the ADA brush after 5 min.     

The inability of Streptococcus mutans and Lactobacillus acidophilus to form a biofilm in vitro on dentine pretreated with ozone

Background: The use of ozone therapy in the treatment of dental caries is equivocal. The aim of this study was to use an in vitro model to determine the effects of prior ozone application to dentine on biofilm formation and to measure any associated reduction in bacteria viability. Methods: Twenty dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials. Ten dentine discs were infused with ozone for 40 seconds, 10 samples remained untreated as a control. The vials were filled with nutrient medium, sterilized and placed into the outflow from a continuous chemostat culture of Streptococcus mutans and Lactobacillus acidophilus for four weeks. At the conclusion of the experiment bacterial growth was monitored by taking optical density readings of the growth medium in each vial and the outer surface of the dentine specimens were examined by scanning electron microscopy as shown by SEM analysis. Results: Ozone infusion prevented biofilm formation on all the treated samples while there was substantial biofilm present on the control specimens. While the average optical density of the control specimens was almost twice that of the ozone infused dentine (0.710 for the control with a SD of 0.288 and 0.446 for the ozonated samples with a SD of 0.371), the results were not significant (p > 0.05). Conclusions: This preliminary study has shown that the infusion of ozone into non‐carious dentine prevented biofilm formation in vitro from S. mutans and L. acidophilus over a four‐week period. The possibility exists that ozone treatment may alter the surface wettability of dentine through reaction with organic constituents.     

The impact of physical therapy on functional outcomes after stroke: what's the evidence?

OBJECTIVE: To determine the evidence for physical therapy interventions aimed at improving functional outcome after stroke. METHODS: MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, PEDro, EMBASE and DocOnline were searched for controlled studies. Physical therapy was divided into 10 intervention categories, which were analysed separately. If statistical pooling (weighted summary effect sizes) was not possible due to lack of comparability between interventions, patient characteristics and measures of outcome, a best-research synthesis was performed. This best-research synthesis was based on methodological quality (PEDro score). RESULTS: In total, 151 studies were included in this systematic review; 123 were randomized controlled trials (RCTs) and 28 controlled clinical trials (CCTs). Methodological quality of all RCTs had a median of 5 points on the 10-point PEDro scale (range 2-8 points). Based on high-quality RCTs strong evidence was found in favour of task-oriented exercise training to restore balance and gait, and for strengthening the lower paretic limb. Summary effect sizes (SES) for functional outcomes ranged from 0.13 (95% Cl 0.03-0.23) for effects of high intensity of exercise training to 0.92 (95% Cl 0.54-1.29) for improving symmetry when moving from sitting to standing. Strong evidence was also found for therapies that were focused on functional training of the upper limb such as constraint-induced movement therapy (SES 0.46; 95% Cl 0.07-0.91), treadmill training with or without body weight support, respectively 0.70 (95% Cl 0.29-1.10) and 1.09 (95% Cl 0.56-1.61), aerobics (SES 0.39; 95% Cl 0.05-0.74), external auditory rhythms during gait (SES 0.91; 95% Cl 0.40-1.42) and neuromuscular stimulation for glenohumeral subluxation (SES 1.41; 95% Cl 0.76-2.06). No or insufficient evidence in terms of functional outcome was found for: traditional neurological treatment approaches; exercises for the upper limb; biofeedback; functional and neuromuscular electrical stimulation aimed at improving dexterity or gait performance; orthotics and assistive devices; and physical therapy interventions for reducing hemiplegic shoulder pain and hand oedema. CONCLUSIONS: This review showed small to large effect sizes for task-oriented exercise training, in particular when applied intensively and early after stroke onset. In almost all high-quality RCTs, effects were mainly restricted to tasks directly trained in the exercise programme.     

Measurement properties of the Dutch version of the Western Ontario Shoulder Instability Index (WOSI)

Background

The Western Ontario Shoulder Instability Index (WOSI) is a disease-specific shoulder questionnaire to measure quality of life in patients with shoulder instability. The aim of the present study was to translate the WOSI into Dutch and assess its principal measurement properties.

Methods

The WOSI was translated into Dutch according to guidelines in the literature. Fifty-two shoulder instability patients completed the questionnaire twice within 2 weeks. We assessed internal consistency (Cronbach’s alpha), test–retest reliability [Intraclass Correlation Coefficient (ICC)], standard error of measurement (SEM), smallest detectable change (SDC) and reliable change index. The Bland–Altman analysis was applied to assess test–retest agreement and floor and ceiling effects were calculated.

Results

Cronbach’s alpha was 0.95 for the total WOSI score (range 0.88–0.95 for the 4 domains). ICC for the total WOSI score was 0.91 (range 0.79–0.90 for domains), SEM was 130.6 for the total WOSI score resulting in a SDC of 362.0, which is 17.3 % of the maximum obtainable score of 2100. Bland–Altman analysis showed no systematic differences or consistent bias between the two assessments. We observed no relevant floor and ceiling effects.

Conclusion

The results of the present study suggest the Dutch version of the WOSI is a reliable tool for clinical assessment and scientific evaluation. It shows high values for Cronbach’s alpha and ICC implying excellent internal consistency and good test–retest reliability.