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Objective To predict the development of arthritis in anticyclic citrullinated peptide antibodies and/or IgM rheumatoid factor positive (seropositive) arthralgia patients. Methods A prediction rule was developed using a prospective cohort of 374 seropositive arthralgia patients, followed for the development of arthritis. The model was created with backward stepwise Cox regression with 18 variables. Results 131 patients (35%) developed arthritis after a median of 12 months. The prediction model consisted of nine variables: Rheumatoid Arthritis in a first degree family member, alcohol non-use, duration of symptoms <12 months, presence of intermittent symptoms, arthralgia in upper and lower extremities, visual analogue scale pain ≥50, presence of morning stiffness ≥1 h, history of swollen joints as reported by the patient and antibody status. A simplified prediction rule was made ranging from 0 to 13 points. The area under the curve value (95% CI) of this prediction rule was 0.82 (0.75–0.89) after 5 years. Harrell's C (95% CI) was 0.78 (0.73–0.84). Patients could be categorised in three risk groups: low (0–4 points), intermediate (5–6 points) and high risk (7–13 points). With the low risk group as a reference, the intermediate risk group had a hazard ratio (HR; 95% CI) of 4.52 (2.42–8.77) and the high risk group had a HR of 14.86 (8.40–28.32). Conclusions In patients presenting with seropositive arthralgia, the risk of developing arthritis can be predicted. The prediction rule that was made in this patient group can help (1) to inform patients and (2) to select high-risk patients for intervention studies before clinical arthritis occurs.

BackgroundThe introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening.MethodsThis study evaluated the discriminative power of FAM19A4/miR124-2 methylation, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping in HPV-positive women with BMD (n = 294) in two Dutch screening trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated.ResultsMethylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16/18 and HPV16/18/31/33/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for FAM19A4/miR124-2 methylation, HPV16/18 and HPV16/18/31/33/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%.ConclusionThe use of FAM19A4/miR124-2 methylation and/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.

eHealth and social media could be of particular benefit to adults with hearing impairment, but it is unknown whether their use of smart devices, apps, and social media is similar to that of the general population. Our aim is to study whether adults with normal hearing and those with impaired hearing differ in their weekly use of smart devices, apps, and social media; reasons for using social media; and benefits from using social media. We used data from a Dutch cohort, the National Longitudinal Study on Hearing. Data were collected from September 2016 to April 2020 using a web-based questionnaire and speech-in-noise test. The results from this test were used to categorize normal hearing and hearing impairment. Outcomes were compared using (multiple) logistic regression models. Adults with impaired hearing (n=384) did not differ from normal hearing adults (n=341) in their use of a smartphone or tablet. They were less likely to make use of social media apps on a smartphone, tablet, or smartwatch (age-adjusted odds ratio [OR] 0.67, 95% CI 0.48-0.92; P=.02). Use of social media on all devices and use of other apps did not differ. Adults with hearing impairment were more likely to agree with using social media to stay in touch with family members (OR 1.54, 95% CI 1.16-2.07; P=.003) and friends (age-adjusted OR 1.35, 95% CI 1.01-1.81; P=.046). Furthermore, they were more likely to agree with using social media to perform their work (age-adjusted OR 1.51, 95% CI 1.04-2.18; P=.03). There were no differences in the experienced benefits from social media. The potential for eHealth is confirmed because adults with hearing impairment are not less likely to use smart devices than their normal hearing peers. Adults with hearing impairment are less likely to use social media apps on a smart device but not less likely to use social media on all types of internet-connected devices. This warrants further research on the types of social media platforms that adults with hearing impairment use and on the type of device on which they prefer to use social media. Given that participants with hearing impairment are more likely than their normal hearing peers to use social media to perform their work, use of social media may be seen as an opportunity to enhance vocational rehabilitation services for persons with hearing impairment.

AimsThe aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.MethodsProliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.ResultsLow proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).ConclusionsLow proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.

Although cystoscopy is a reliable tool for detecting bladder cancer (BC) in patients with hematuria, it is invasive, costly and often unnecessary since most patients with hematuria do not have BC. Consequently, developing urinary biomarkers for non-invasive BC detection is a major clinical need. While DNA methylation markers hold promise, diagnostic performance can still be improved. We assessed 11 candidate methylation markers for urinary BC detection. Urine samples from 77 primary BC patients and 69 controls were used for marker selection and training, with independent validation conducted on samples from 63 primary BC patients and 71 controls. Samples were self-collected at home, mailed to the hospital and analyzed via quantitative methylation-specific polymerase chain reaction. Marker performance was evaluated through univariable and multivariable logistic regression analyses. Decision curve analysis (DCA) gauged clinical utility by potential cystoscopy reduction. Evaluation identified three most promising markers: NRN1 , GALR1 , and HAND2 . These markers exhibited significantly elevated methylation levels in BC compared to controls in both cohorts ( P  < 0.001). The combined marker set demonstrated an area under the curve (AUC) of 0.94 at 84% (95% CI: 76–92%) sensitivity and 96% (95% CI: 91–100%) specificity. Validation yielded nearly equivalent accuracy (AUC 0.89, sensitivity 76% (95% CI: 65–86%), specificity 93% (95% CI: 86–99%)). DCA indicated a potential of 20 to 35% reduction in cystoscopies depending on the clinical scenario. The excellent diagnostic potential of our methylation markers for non-invasive BC detection, emphasizes their significance for future diagnostic strategies.

Purpose Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the outcome in our centre. Methods A retrospective chart analysis with survival analyses was performed combined with fluorescence in situ hybridization (FISH) analysis to assess CRTC1/3 MAML 2 fusion gene presence. Results Sixty-four cases of MEC were identified. Median age at presentation was 51.4 years with a predominance for parotid gland involvement. Five, 10- and 20- year disease-free survival was 98%, 90% and 68%, respectively. Overall survival was 94%, 90% and 64%, respectively. Local recurrence was seen up to 14 years after primary diagnosis; distant metastases were diagnosed up to 17 years later. The overall recurrence rate was less than 20 per cent. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. Conclusion MEC of the head and neck has a favorable outcome with the exception of high-grade MEC. PNI and nodal involvement are not rare. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. The tendency for late onset of loco-regional and distant recurrence should not be underestimated.

BackgroundHead and neck cancer (HNC) patients often suffer from distress attributed to their cancer diagnosis which may disturb their sleep. However, there is lack of research about poor sleep quality among newly diagnosed HNC patients. Therefore, our aim was to investigate the prevalence and the associated factors of poor sleep quality among HNC patients before starting treatment.Materials and methodsA cross-sectional study was conducted using the baseline data from NET-QUBIC study, an ongoing multi-center cohort of HNC patients in the Netherlands. Poor sleep quality was defined as a Pittsburgh Sleep Quality Index (PSQI) total score of > 5. Risk factors examined were sociodemographic factors (age, sex, education level, living situation), clinical characteristics (HNC subsite, tumor stage, comorbidity, performance status), lifestyle factors, coping styles, and HNC symptoms.ResultsAmong 560 HNC patients, 246 (44%) had poor sleep quality before start of treatment. Several factors were found to be significantly associated with poor sleep: younger age (odds ratio [OR] for each additional year 0.98, 95% CI 0.96–1.00), being female (OR 2.6, 95% CI 1.7–4.1), higher passive coping style (OR 1.18, 95% CI 1.09–1.28), more oral pain (OR 1.10, 95% CI 1.01–1.19), and less sexual interest and enjoyment (OR 1.13, 95% CI 1.06–1.20).ConclusionPoor sleep quality is highly prevalent among HNC patients before start of treatment. Early evaluation and tailored intervention to improve sleep quality are necessary to prepare these patients for HNC treatment and its consequences.

BackgroundThe majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing of 26 weeks. With B-cell-guided dosing patients receive their next dose when B-cell repopulation occurs. Prediction of B-cell repopulation using ocrelizumab concentrations could aid in personalising treatment regimes. The objectives of this study were to evaluate the association between ocrelizumab drug concentration, antidrug antibodies (ADAs) and CD19 B-cell count, and to define a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 CD19+ B cells/µL).MethodsIn this investigator-initiated prospective study, blood samples at various time points during ocrelizumab treatment were collected from a biobank. Serum ocrelizumab concentrations and ADAs were measured with two different assays developed for this study. Data were analysed using linear mixed effect models. An receiver operating characteristic (ROC) curve was used to determine a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 cells/µL).ResultsA total of 452 blood samples from 72 patients were analysed. Ocrelizumab concentrations were detectable up until 53.3 weeks after last infusion and ranged between <0.0025 and 204 µg/mL after 1–67 weeks. Ocrelizumab concentration was negatively associated with B-cell count, with body mass index identified as effect modifier. We found a cut-off value of 0.06 µg/mL for start of B-cell repopulation of ≥10 cells/µL. Ocrelizumab ADAs were detectable in four patients (5.7%) with corresponding low ocrelizumab concentrations and start of B-cell repopulation.ConclusionsSerum ocrelizumab concentration was strongly associated with B-cell count. Measurement of ocrelizumab drug concentrations and ADAs could play an important role to further personalise treatment and predict the start of B-cell repopulation.

For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases. Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0–2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8. Although at the operator's discretion, a minimally invasive approach in both treatment groups was recommended. The primary endpoint was overall survival, assessed in the intention-to-treat population. A hazard ratio (HR) of 1·30 was considered the upper limit of non-inferiority for the primary endpoint. A preplanned interim analysis with predefined stopping rules for futility (conditional power to prove the null hypothesis <20%) and early benefit (conditional power >90%, superior safety outcomes for the experimental group, and no difference or superiority regarding local control for the experimental group) was done 12 months after enrolment of 50% of the planned sample size. Safety was assessed per treatment group. This trial is registered with ClinicalTrials.gov, NCT03088150. Between Aug 7, 2017, and Feb 14, 2024, 300 patients were randomly assigned to the experimental group (n=148, 100 male [68%] and 48 female [32%]; median age 67·9 years [range 29·2–85·7]) or to the control group (n=148, 107 male [72%] and 41 female [28%]; median age 65·1 [range 31·4–87·4]); four patients (two in each treatment group) were excluded after randomisation because they were found to have other disease pathology. Median follow-up at the prespecified interim analysis was 28·9 months (range 0·3–77·8). The trial was stopped early for meeting the predefined stopping rules: (1) a conditional likelihood to prove non-inferiority for overall survival of 90·5% (median overall survival not reached in both groups; HR 1·05; 95% CI 0·69–1·58; p=0·83), (2) a non-inferior local control (median local control not reached in both groups; HR 0·13, 95% CI 0·02–1·06; p=0·057), and (3) a superior safety profile for the experimental group. Patients in the experimental group had fewer adverse events than those in the control group (28 [19%] vs 67 [46%]; p<0·0001). Serious adverse events occurred in 11 (7%) of 148 patients in the experimental group and 29 (20%) of 146 in the control group, mostly periprocedural haemorrhage requiring intervention (one [1%] vs eight [5%]), and infectious complications requiring intervention (six [4%] vs 11 [8%]). There were no treatment-related deaths in the experimental group and three treatment-related deaths (2%) in the control group (two due to postoperative cardiac complications and one due to sepsis and liver failure). The assumption that thermal ablation should be reserved for unresectable colorectal liver metastases requires re-evaluation and the preferred treatment should be individualised and based on clinical characteristics and available expertise. Medtronic-Covidien.

Purpose The aim of this study was to explore the perceived need for supportive care including healthy lifestyle programs among cancer survivors, their attitude towards self-management and eHealth, and its association with several sociodemographic and clinical variables and quality of life. Methods A questionnaire on the perceived need for supportive care and attitude towards self-management and eHealth was completed by 212 cancer survivors from an online panel. Results Highest needs were reported regarding physical care (66 %), followed by healthy lifestyle programs (54 %), social care (43 %), psychological care (38 %), and life question-related programs (24 %). In general, cancer survivors had a positive attitude towards self-management and eHealth. Supportive care needs were associated with male gender, lower age, treatment with chemotherapy or (chemo)radiation (versus surgery alone), hematological cancer (versus skin cancer, breast cancer, and other types of cancer), and lower quality of life. A positive attitude towards self-management was associated with lower age. A more positive attitude towards eHealth was associated with lower age, higher education, higher income, currently being under treatment (versus treatment in the last year), treatment with chemotherapy or (chemo)radiation (versus surgery alone), prostate and testicular cancer (versus hematological, skin, gynecological, and breast cancer and other types of cancer), and lower quality of life. Conclusions The perceived need for supportive care including healthy lifestyle programs was high, and in general, cancer survivors had a positive attitude towards self-management and eHealth. Need and attitude were associated with sociodemographic and clinical variables and quality of life. Therefore, a tailored approach seems to be warranted to improve and innovate supportive care targeting cancer survivors.