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Τετάρτη 3 Φεβρουαρίου 2021

Factors associated with under-reporting of head and neck squamous cell carcinoma in cause-of-death records: A comparative study of two national databases in France from 2008 to 2012

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journal.pone.0246252.g005&size=inline

by Caroline Even, Luis Sagaon Teyssier, Yoann Pointreau, Stéphane Temam, Florence Huguet, Lionnel Geoffrois, Michaël Schwarzinger, on behalf of the EPICORL Study Group

Objective

To date, no study has evaluated the detection rate of head and neck squamous cell carcinoma (HNSCC) in cause-of-death records in Europe. Our objectives were to compare the number of deaths attributable to HNSCC from two national databases in France and to identify factors associated with under-reporting of HNSCC in cause-of-death records.

Methods

The national hospital discharge database and the national underlying cause-of-death records were compared for all HNSCC-attributable deaths in adult patients from 2008 to 2012 in France. Factors associated with under-reporting of HNSCC in cause-of-death records were assessed using multivariate Poisson regression.

Results

A total of 41,503 in-hospital deaths were attributable to HNSCC as compared to 25,647 deaths reported in national UCoD records (a detection rate of 62%). Demographics at death were similar in both databases with respect to gender (83% men), age (54% premature deaths at 25–64 years), and geographi c distribution. In multivariate Poisson regression, under-reporting of HNSCC in cause-of-death records significantly increased in 2012 compared to 2010 (+7%) and was independently associated with a primary HNSCC site other than the larynx, a former primary or second synchronous cancer other than HNSCC, distant metastasis, palliative care, and death in hospitals other than comprehensive cancer care centers. The main study results were robust in a sensitivity analysis which also took into account deaths outside hospital (overall, 51,129 HNSCC-attributable deaths; a detection rate of 50%). For the year 2012, the age-standardized mortality rate for HNSCC derived from underlying cause-of-death records was less than half that derived from hospital discharge summaries (14.7 compared to 34.1 per 100,000 for men and 2.7 compared to 6.2 per 100,000 for women).

Conclusion

HNSCC is largely under-reported in cause-of-death records. This study documents the value of national hospital disch arge databases as a complement to death certificates for ascertaining cancer deaths.

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Prediction of aortic valve regurgitation after continuous-flow left ventricular assist device implantation using artificial intelligence trained on acoustic spectra

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Abstract

Significant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as "present"; the other 219 episodes were characterized as "none". Wavelet (time–frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched usi ng an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time–frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD.

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Efficacy of Agomelatine 25–50 mg for the Treatment of Anxious Symptoms and Functional Impairment in Generalized Anxiety Disorder: A Meta-Analysis of Three Placebo-Controlled Studies

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Abstract

Introduction

The purpose of this study is to investigate the effects of agomelatine on anxious symptoms and functional impairment in a pooled dataset from randomized placebo-controlled trials for generalized anxiety disorder (GAD).

Methods

Data from three randomized, placebo-controlled trials that evaluated the efficacy of agomelatine 25–50 mg were pooled. The short-term (12 weeks) efficacy of agomelatine was assessed in regards to (1) anxious symptoms using the Hamilton Anxiety Scale (HAM-A), and (2) functional impairment using the Sheehan Disability Scale (SDS). Meta-analysis using a random effect model was used to assess differences between groups. Remission and response rates for the HAM-A and SDS were calculated, and analyses were repeated in participants with more severe anxiety symptoms.

Results

In total, 669 patients (340 on agomelatine; 329 on placebo) were included in the analyses. Compared to placebo, the agomelatine group had a significant reduction in HAM-A total score at week 12 (between group difference: 6.30 ± 2.51, p = 0.012). Significant effects were also found for symptom response on the HAM-A (67.1% of patients on agomelatine vs. 32.5% on placebo) and symptom remission (38.8% of patients on agomelatine vs. 17.3% on placebo). Compared to placebo, there was a significant difference in favour of the agomelatine group at week 12 on the SDS total score (5.11 ± 1.81, p = 0.005). Significant effects were also found for functional response on the SDS (79.1% of patients on agomelatine vs. 43.2% of placebo) and functional remission (55.2% of patients on agomelatine vs. 25.4% on placebo). All findings for anxious symptoms and functional impairment were confirmed in the subset of more severely anxious patients. Agom elatine was well tolerated by patients.

Conclusion

This meta-analysis confirms that agomelatine reduces anxiety symptoms and improves the global functioning of GAD patients.

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The effect on subsequent fracture risk of age, sex, and prior fracture site by recency of prior fracture

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Abstract

Summary

The risk of a recurrent fragility fracture varies by age and sex, as by site and recency of sentinel fracture.

Introduction

The recency of prior fractures affects subsequent fracture risk. Variable recency may obscure other factors that affect subsequent fracture risk. The aim of this study was to quantify the effect of a sentinel fracture by site, age, and sex where the recency was held constant.

Methods

The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture incidence was compared to that of the general population determined at fixed times after a sentinel fracture (humeral, clinical vertebral, forearm, hip, and minor fractures). Outcome fractures comprised a major osteoporotic fracture and hip fracture.

Results

Sentinel osteoporotic fractures were identified in 9504 men and women. Of these, 3616 individuals sustained a major osteoporotic fracture as the first subsequent fracture, of whom 1799 sustained a hip fracture. Hazard ratios for prior fracture were consistently higher in men than in women and decreased progressively with age. Hazard ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus, forearm, or minor osteoporotic fracture.

Conclusion

The risk of a recurrent fragility fracture varies by age, sex, and site of sentinel fracture when recency is held constant.

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Efficacy of platelet-rich plasma injection in comparison to physical therapy for treatment of chronic partial supraspinatus tear

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Abstract

Background

Supraspinatus tendon is a part of the rotator cuff of the shoulder, partial or full-thickness tear can affect the tendon secondary to trauma or repeated microtrauma. The aim of the present study is to evaluate the efficacy of platelet-rich plasma (PRP) injection in comparison to physical therapy for treatment of chronic partial supraspinatus tears.

Results

At the beginning of the study, there were no significant differences between both groups in all parameters: (a) PRP injection had significantly improved the visual analog scale (VAS), disabilities of arm, shoulder and hand scale (DASH) and shoulder range of motion (ROM) but not size of tear at 6 and 12 weeks post-injection in comparison to baseline recordings; (b) physical therapy had significantly improved VAS, DASH but not shoulder ROM nor size of tear at 6 and 12 weeks post-injection in comparison to baseline recordings; and (c) PRP injection was superior to physical therapy in the improvement of VAS, shoulder ROM, and DASH score.

Conclusion

The US-guided PRP injection is superior to physical therapy in improving pain, ROM, and function in treatment of partial thickness tear of supraspinatus tendon.

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Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data

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Abstract

Introduction

Although clinical guidelines are broadly available, the relationship between adherence and outcomes is not well studied. This study aimed to assess the association between adherence to National Comprehensive Cancer Network (NCCN) guidelines and clinical outcomes for adult patients with advanced non-small-cell lung cancer (aNSCLC).

Methods

This was a retrospective cohort study of adult patients with aNSCLC (stages IIIB, IIIC, and IV) from a de-identified real-world database. The objective was accomplished in a two-step analysis process. We first assessed adherence to NCCN recommendations for biomarker testing and overall survival (OS). Next, we assessed adherence to NCCN-recommended first-line therapy and time to treatment discontinuation (TTD). Multivariable Cox regression analyses were conducted to evaluate the association between guideline adherence and patient outcomes. Kaplan–Meier analyses were used to assess median OS and TTD.

Results

A total of 28,784 patients with a diagnosis for aNSCLC between January 1, 2011 and July 31, 2019 met the inclusion criteria for the analysis of NCCN-recommended biomarker testing adherence. Two-thirds of these patients (n = 19,787) had evidence of biomarker testing (adherent). Multivariable Cox models found that testing-adherent patients had a significantly lower risk of mortality [hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.86, 0.92; p < 0.01]. Median OS was modestly longer in the testing-adherent group compared to the testing-non-adherent group (15.4 vs. 14.2 months; p < 0.01). For the first-line therapy analysis, 15,898 patients met the inclusion criteria, of which 69.9% had evidence of appropriate first-line therapy (first-line-adherent). The multivariable Cox model found that adherent patients had significantly lower risk of treatment discontinuation versus non-adher ent patients (HR = 0.60, 95% CI 0.57, 0.62; p < 0.01). First-line-adherent patients had a modest, yet significantly longer median TTD compared to first-line-non-adherent patients (3.45 vs. 2.40 months; p < 0.01).

Conclusions

Improved clinical outcomes were observed in patients who were adherent to NCCN-recommended biomarker testing and first-line therapy. This study demonstrated the value of following NCCN guideline recommendations and the need to prioritize timely access to biomarker testing and individualized treatment.

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Gastrointestinal dysfunction in movement disorders

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Abstract

Purpose of review

This article provides an overview of the clinical presentation, investigations, and treatment options for gastrointestinal tract (GIT) dysfunction in patients with Parkinson's disease (PD) and other movement disorders.

Recent findings

GIT dysfunction commonly appears as constipation and fecal incontinence (mostly overflow, accompanied with sphincter failure in multiple system atrophy [MSA]). Bowel dysfunction (underactive) occurs irrespectively from the site of the neurologic lesion, which is in contrast to site-dependent bladder dysfunction (brain, overactive; periphery, underactive). GI emergencies may arise, including intestinal pseudo-obstruction, intussusception, volvulus, and stercoral ulcer (ulcer of the colon due to pressure and irritation resulting from severe, prolonged constipation). Bowel function tests in neurologic patients often show a combination of slow transit and anorectal dysfunction. Management for slow transit constipation includes bulking agents, softening agents, yogurt/probiotics, and prokinetic agents. Suppositories, botulinum toxin injections, and transanal irrigation are options for managing anorectal constipation.

Conclusions

Function of the bowel is commonly affected in PD and other movement disorders. Neurologists play an important role in assessing bowel symptoms in their patients and planning treatment strategies, often in collaboration with specialist teams.

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Headache Gauge: a real-life calendar-based tool for headache monitoring

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Abstract

Background

This study aimed to validate a semi-quantitative composite score tool, "Headache Gauge" (HG), to monitor the treatment effect in primary headaches in everyday clinic practice, adjustable to any chosen timeframe.

Method

A cohort validation study of HG was performed in primary headache patients, recovering their clinical data and patient-related outcome measures (PROMs) for headache (HIT-6, MIDAS, HURT), work impact (WPAIQ), quality-of-life (SF-12), and mood (STAI, ZUNG). HG score distribution, its relation to clinical variables, its internal consistency, and its convergent validity were determined.

Results

HG was plotted in 233 patients: 90.1% females, age average 37 years, 86% with migraine, 27% with chronic headaches, and 28% with medication overuse. HG ranged from 0.21 to 58.3 in this sample, higher in chronic headaches (HG 16) and medication overuse (HG 15). HG presented good concurrent validity, significantly correlating with HIT-6 (p < 0.0001), SF-12 (p = 0.001), WPAIQ (p < 0.0001), MIDAS (p < 0.0001), and HURT (p < 0.0001). Good sensitivity to change (p < 0.001) and moderate test-retest reliability (p = 0.001) were calculated after reassessment of 147 patients (63.1% of the initial sample).

Conclusions

Headache Gauge is a clinical data-based outcome measure that conceptually translates the percentage of lost time to headache in any given timeframe. It relates to headache impact, therefore bearing the potential to be relevant in real-life clinical monitoring.

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The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases

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Abstract

Background

IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.

Case presentation

Two ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave's disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neuros urgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.

Conclusions

A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

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Neutral endopeptidase depletion decreases colon cancer cell proliferation and TGF-β1 synthesis in indirect co-cultures with normal colon fibroblasts

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Abstract

Purpose

Although recent studies have suggested that neutral endopeptidase (NEP) is implicated in the regulation of colon cancer (CC) cell growth and metastasis, the influence of the tumor microenvironment on this role of NEP has not been investigated so far. Normal colon fibroblasts (NCFs) constitute a component of the stroma surrounding a tumor in an early stage of its development. NCFs can influence transformed cells via different paracrine factors, including TGF-β1. This in vitro study was undertaken to evaluate the role of NEP in CC promotion in conditions of indirect co-culture of CC cells (LS180 and SW620) with NCFs (CCD-18Co) or their conditioned medium (CM-18Co).

Methods

We examined cell proliferation (with the BrdU assay) and invasiveness (using BME-coated inserts, 8 µm) of NEP-expressing, NEP-silenced (siRNA), and NEP-inhibited (with thiorphan, i.e. a NEP specific inhibitor) CC cells cultured alone or co-cultured with CCD-18Co or with their conditioned medium. The Western blot and ELISA methods were used to assess the level of TGF-β1.

Results

The results showed that the co-culture of the NEP-depleted CC cells with NCFs or their conditioned medium resulted in a significant decrease in cell proliferation in comparison with the proliferative potential of NEP-silenced/inhibited CC cells cultivated alone. In contrast, the NEP depletion did not influence the invasiveness of CC cells in the co-cultures. The co-culture of CC cells with CCD-18Co or CM-C18Co resulted in increased synthesis of TGF-β1, while the NEP downregulation decreased the synthesis of TGF-β1 in CC cells and abolished the stimulatory effect of the co-cultures on TGF-β1 production.

Conclusions

The results suggest that the expression of NEP by colon cancer cells is essential for their proliferation and TGF-β1 synthesis during paracrine interactions with NCFs.

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Τρίτη 2 Φεβρουαρίου 2021

Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group

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Abstract

The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

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