Epidemiology of diagnosed cluster headache in Norway

Background: Cluster headache (CH) is one of the most painful conditions in humans and there is limited epidemiological data on this debilitating condition. Objectives: To describe the epidemiology of CH in Norway Methods: We conducted a nationwide study to investigate the prevalence, incidence, and comorbidity of CH in Norway between January 1 2008 and December 31 2016. Treatment and outcome data from the Norwegian patient registry and the Norwegian prescription database were linked on an individual basis. Results: Among 3,892,260 individuals ≥18 years old of age, we identified a total of 1891 patients with CH. The prevalence of CH was 48.6 per 100,000, and the male-to-female ratio was 1.47. The estimated incidence of CH was 3.0 per 100,000/year. Among patients with CH, increased age and sex adjusted odds ratios ([OR], all with p-values <0.0001, were observed for medication-induced headache (OR 50.7, 95% CI 36.7–69.9), migraine (OR 25.2, 95% CI 22.5–28.3), chronic posttraumatic headache (OR 22.2, 95% CI 12.8–38.45), history of cranial trauma (OR 1.9, 95% CI 1.5–2.4), somatoform disorders (OR 4.2, 95% CI 3.0–5.8), suicide attempt (OR 3.9, 95% CI 2.6–5.8), personality disorder (OR 3.6, 95% CI 2.6–4.9), bipolar disorder (OR 3.6, 95% CI 2.8–4.8), peptic ulcer (OR 2.8, 95% CI 2.3–3.3), depression (OR 2.8, 95% CI 2.4–3.1), substance abuse (OR 2.6, 95% CI 2.0–3.3), and cerebrovascular disease (OR 2.4, 95% CI 1.8–3.1). Use of opioid analgesics during the study period was more common among patients with CH compared to others (81% vs. 22%, sex and age adjusted OR 23.4, 95% CI 20.8–26.2, p < 0.0001)

Interobserver agreement and prognostic impact for MRI–based 2018 FIGO staging parameters in uterine cervical cancer

Objectives To evaluate the interobserver agreement for MRI–based 2018 International Federation of Gynecology and Obstetrics (FIGO) staging parameters in patients with cervical cancer and assess the prognostic value of these MRI parameters in relation to other clinicopathological markers. Methods This retrospective study included 416 women with histologically confirmed cervical cancer who underwent pretreatment pelvic MRI from May 2002 to December 2017. Three radiologists independently recorded MRI–derived staging parameters incorporated in the 2018 FIGO staging system. Kappa coefficients (κ) for interobserver agreement were calculated. The predictive and prognostic values of the MRI parameters were explored using ROC analyses and Kaplan–Meier with log-rank tests, and analyzed in relation to clinicopathological patient characteristics. Results Overall agreement was substantial for the staging parameters: tumor size > 2 cm (κ = 0.80), tumor size > 4 cm (κ = 0.76), tumor size categories (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) (κ = 0.78), parametrial invasion (κ = 0.63), vaginal invasion (κ = 0.61), and enlarged lymph nodes (κ = 0.63). Higher MRI–derived tumor size category (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) was associated with a stepwise reduction in survival (p ≤ 0.001 for all). Tumor size > 4 cm and parametrial invasion at MRI were associated with aggressive clinicopathological features, and the incorporation of these MRI–based staging parameters improved risk stratification when compared to corresponding clinical assessments alone. Conclusion The interobserver agreement for central MRI–derived 2018 FIGO staging parameters was substantial. MRI improved the identification of patients with aggressive clinicopathological features and poor survival, demonstrating the potential impact of MRI enabling better prognostication and treatment tailoring in cervical cancer.publishedVersio

What MRI-based tumor size measurement is best for predicting long-term survival in uterine cervical cancer?

Background: Tumor size assessment by MRI is central for staging uterine cervical cancer. However, the optimal role of MRI-derived tumor measurements for prognostication is still unclear. Material and methods: This retrospective cohort study included 416 women (median age: 43 years) diagnosed with cervical cancer during 2002–2017 who underwent pretreatment pelvic MRI. The MRIs were independently read by three radiologists, measuring maximum tumor diameters in three orthogonal planes and maximum diameter irrespective of plane (MAXimaging). Inter-reader agreement for tumor size measurements was assessed by intraclass correlation coefficients (ICCs). Size was analyzed in relation to age, International Federation of Gynecology and Obstetrics (FIGO) (2018) stage, histopathological markers, and disease-specific survival using Kaplan–Meier-, Cox regression-, and time-dependent receiver operating characteristics (tdROC) analyses. Results: All MRI tumor size variables (cm) yielded high areas under the tdROC curves (AUCs) for predicting survival (AUC 0.81–0.84) at 5 years after diagnosis and predicted outcome (hazard ratios [HRs] of 1.42–1.76, p < 0.001 for all). Only MAXimaging independently predicted survival (HR = 1.51, p = 0.03) in the model including all size variables. The optimal cutoff for maximum tumor diameter (≥ 4.0 cm) yielded sensitivity (specificity) of 83% (73%) for predicting disease-specific death after 5 years. Inter-reader agreement for MRI-based primary tumor size measurements was excellent, with ICCs of 0.83–0.85. Conclusion: Among all MRI-derived tumor size measurements, MAXimaging was the only independent predictor of survival. MAXimaging ≥ 4.0 cm represents the optimal cutoff for predicting long-term disease-specific survival in cervical cancer. Inter-reader agreement for MRI-based tumor size measurements was excellent.publishedVersio

The North Carolina Physical Activity Policy Research Center: Making Connections with North Carolina Planners

Physical activity participation for youth and adults is suboptimal in North Carolina. There is growing interest among policy makers to promote physical activity, yet research in this area is limited. The North Carolina Physical Activity Policy Research Center was established in 2004 to conduct research on physical activity and policy. This cross-disciplinary center brings together faculty and researchers from the University of North Carolina School of Public Health and the College of Arts and Sciences. Current projects include understanding and documenting polices that affect walking and bicycling to school, trail development, and community planning decisions related to physical activity

The North Carolina Physical Activity Policy Research Center: Making Connections with North Carolina Planners

Physical activity participation for youth and adults is suboptimal in North Carolina. There is growing interest among policy makers to promote physical activity, yet research in this area is limited. The North Carolina Physical Activity Policy Research Center was established in 2004 to conduct research on physical activity and policy. This cross-disciplinary center brings together faculty and researchers from the University of North Carolina School of Public Health and the College of Arts and Sciences. Current projects include understanding and documenting polices that affect walking and bicycling to school, trail development, and community planning decisions related to physical activity

Preoperative pelvic MRI and 2-[18F]FDG PET/CT for lymph node staging and prognostication in endometrial cancer—time to revisit current imaging guidelines?

Objective This study presents the diagnostic performance of four different preoperative imaging workups (IWs) for prediction of lymph node metastases (LNMs) in endometrial cancer (EC): pelvic MRI alone (IW1), MRI and [18F]FDG-PET/CT in all patients (IW2), MRI with selective [18F]FDG-PET/CT if high-risk preoperative histology (IW3), and MRI with selective [18F]FDG-PET/CT if MRI indicates FIGO stage ≥ 1B (IW4). Methods In 361 EC patients, preoperative staging parameters from both pelvic MRI and [18F]FDG-PET/CT were recorded. Area under receiver operating characteristic curves (ROC AUC) compared the diagnostic performance for the different imaging parameters and workups for predicting surgicopathological FIGO stage. Survival data were assessed using Kaplan-Meier estimator with log-rank test. Results MRI and [18F]FDG-PET/CT staging parameters yielded similar AUCs for predicting corresponding FIGO staging parameters in low-risk versus high-risk histology groups (p ≥ 0.16). The sensitivities, specificities, and AUCs for LNM prediction were as follows: IW1—33% [9/27], 95% [185/193], and 0.64; IW2—56% [15/27], 90% [174/193], and 0.73 (p = 0.04 vs. IW1); IW3—44% [12/27], 94% [181/193], and 0.69 (p = 0.13 vs. IW1); and IW4—52% [14/27], 91% [176/193], and 0.72 (p = 0.06 vs. IW1). IW3 and IW4 selected 34% [121/361] and 54% [194/361] to [18F]FDG-PET/CT, respectively. Employing IW4 identified three distinct patient risk groups that exhibited increasing FIGO stage (p < 0.001) and stepwise reductions in survival (p ≤ 0.002). Conclusion Selective [18F]FDG-PET/CT in patients with high-risk MRI findings yields better detection of LNM than MRI alone, and similar diagnostic performance to that of MRI and [18F]FDG-PET/CT in all.publishedVersio

Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development

Background: Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings: Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions: HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies.publishedVersio

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome

Objective CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy. Design Multicentre cohort study. Patients Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) ≥0.35 were treated with a single dose of CHF5633 within 48 hours after birth. The first 20 received 100 mg/kg and the second 20 received 200 mg/kg. Outcome measures Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue. Results Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100 mg/kg cohort and 53 AEs by 20 infants in the 200 mg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200 mg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected. Conclusions Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials