What's in a name? A call to reframe non-communicable diseases.

The global health community does not spend much time on branding, which perhaps explains why existing classifications for the three largest groups of diseases are both outdated and counterproductive. The first Global Burden of Disease study1 described infectious diseases, non-communicable diseases (NCDs), and injuries. This grouping reflected a predominantly infectious disease burden in low-income and middle-income countries, which has since tilted towards NCDs. A name that is a longwinded non-definition, and that only tells us what this group of diseases is not, is not befitting of a group of diseases that now constitute the world's largest killer

Detection of human papillomavirus in laryngeal squamous cell carcinoma: systematic review and meta-analysis

Background: Recent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies. Objective To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC. Methods Literature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [CI]), with homogeneity testing using Cochran's Q and I2 statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size. Potential publication bias was estimated using funnel plot symmetry. Results One hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non–polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both. Conclusions Variability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression

Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer

IntroductionOutcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence.MethodsWe probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections.ResultsThe tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells.ConclusionThus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome

Thalamus and focal to bilateral seizures: A multiscale cognitive imaging study.

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality. METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality. RESULTS: Individuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS. CONCLUSIONS: In TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Volumetric and microstructural abnormalities of the amygdala in focal epilepsy with varied levels of SUDEP risk

Although the mechanisms of sudden unexpected death in epilepsy (SUDEP) are not yet well understood, generalised- or focal-to-bilateral tonic-clonic seizures (TCS) are a major risk factor. Previous studies highlighted alterations in structures linked to cardio-respiratory regulation; one structure, the amygdala, was enlarged in people at high risk of SUDEP and those who subsequently died. We investigated volume changes and the microstructure of the amygdala in people with epilepsy at varied risk for SUDEP since that structure can play a key role in triggering apnea and mediating blood pressure. The study included 53 healthy subjects and 143 patients with epilepsy, the latter separated into two groups according to whether TCS occur in years before scan. We used amygdala volumetry, derived from structural MRI, and tissue microstructure, derived from diffusion MRI, to identify differences between the groups. The diffusion metrics were obtained by fitting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. The analyses were performed at the whole amygdala level and at the scale of amygdaloid nuclei. Patients with epilepsy showed larger amygdala volumes and lower neurite density indices (NDI) than healthy subjects; the left amygdala volumes were especially enhanced. Microstructural changes, reflected by NDI differences, were more prominent on the left side and localized in the lateral, basal, central, accessory basal and paralaminar amygdala nuclei; basolateral NDI lowering appeared bilaterally. No significant microstructural differences appeared between epilepsy patients with and without current TCS. The central amygdala nuclei, with prominent interactions from surrounding nuclei of that structure, project to cardiovascular regions and respiratory phase switching areas of the parabrachial pons, as well as to the periaqueductal gray. Consequently, they have the potential to modify blood pressure and heart rate, and induce sustained apnea or apneusis. The findings here suggest that lowered NDI, indicative of reduced dendritic density, could reflect an impaired structural organization influencing descending inputs that modulate vital respiratory timing and drive sites and areas critical for blood pressure control