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OBJECTIVES: This narrative review aims to present the concept of value in imaging and explore why we conduct low-value procedures, how to reduce this wasteful use, and what we could gain from reducing low-value imaging. KEY FINDINGS: Imaging of low value to the patient contributes to thousands of metric tons of CO2 emissions, costing several billion US dollars annually. With a 20% reduction in low-value imaging, we would reduce the waste of resources related to 7.2 million procedures and, at the same time, reduce the risk of incidentalomas, overdiagnosis, and overtreatment and reduce wait times for patients in need of imaging services of high value. Multi-component initiatives targeting barriers in all levels of society and healthcare are needed to reduce low-value imaging. Radiographers are key actors in medical imaging and can make substantial contributions to this effort by, together with the radiologists, referrers, and managers, ensuring that all imaging procedures conducted are sustainable along four dimensions of sustainability: value, cost, risk, and environment. CONCLUSION: Efforts to secure sustainable imaging considering the four crucial dimensions (value, cost, radiation, and environment) should be made at all levels of society and healthcare, from governmental management to the individual healthcare worker. Radiographers are vital in obtaining sustainability to ensure only sustainable imaging procedures are conducted. IMPLICATIONS FOR PRACTICE: When assessing the appropriateness of imaging procedures, we need to consider the environment, safety, effectiveness, and efficiency. To obtain this, we need a collective and coordinated effort locally, nationally, and internationally to deliver sustainable imaging services.
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BACKGROUND: Manual semen assessment (MSA) is a key component in a male's fertility assessment. Clinicians rely on it to make diagnostic and treatment decisions. When performed manually, this routine laboratory test is prone to variability due to human intervention which can lead to misdiagnosis and consequently over- or under- treatment. For standardisation, continuous training, quality control (QC) programs and pricy Computer-Assisted Sperm Analysis (CASA) systems have been proposed, yet, without resolving intra- and inter-laboratory variability. In response, promising simplified sperm testing devices, able to provide cost-effective point-of-care male infertility diagnosis are prospected as a plausible solution to resolve variability and increase access to sperm testing. MATERIALS AND METHODS: A throughout literature research for semen testing, sperm analysis, smart-phone assisted semen analysis, 'at-home' semen testing, male infertility, infertility in developing countries, infertility in low- and middle-income countries (LMIC) and quantitative sperm analysis was performed. A total of 14 articles, specific to 'at-home' simplified sperm assessment, were included to treat the core subject. RESULTS: Continuous training and consistent QC, are sine qua none conditions to achieve accurate and comparable MSA. Compliance does not rule-out variability, nevertheless. Emerging simplified sperm assessment devices are an actual alternative to resolve the lack of standardisation and accessibility to sperm analysis. YO ® , SEEM ® , and ExSeed ® are commercially available, user-friendly smartphone-based devices which can accurately measure volume, sperm concentration (millions/ml) and total motile sperm count. More broadly, by cost-effectiveness, availability, accuracy and convenient application, these devices could effectively select patients for first-line artificial reproduction treatments such as intrauterine insemination. CONCLUSIONS: Accuracy and cost-effectiveness make smart-phone based sperm testing devices a practical and realistic solution to overcome variability in MSA. Importantly, these tools represent an actual opportunity to standardise and improve male subfertility diagnosis and treatment, especially in LMIC. However, before clinical application is possible, guidelines, further testing with special attention on accuracy in washed sperm, availability, cost-benefit and reliability are required.
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AIMS: Curative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT. MATERIALS AND METHODS: Information on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis. RESULTS: Data from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events. CONCLUSION: The distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.
Subject(s)
Chemoradiotherapy , Head and Neck Neoplasms , Mortality , Radiotherapy , Risk Assessment , Squamous Cell Carcinoma of Head and Neck , Chemoradiotherapy/methods , Chemoradiotherapy/mortality , Chemoradiotherapy/statistics & numerical data , Databases, Factual , Denmark/epidemiology , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Quality Indicators, Health Care , Radiation Oncology/standards , Radiotherapy/methods , Radiotherapy/mortality , Radiotherapy/statistics & numerical data , Risk Assessment/methods , Risk Assessment/standards , Risk Factors , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Time FactorsABSTRACT
Purpose The aim of this study was to assess short and long-term effectiveness of brief coping-focused psychotherapy (Brief-PsT) compared with short-term psychotherapy (Short-PsT) on work-participation (WP) and mental health. Both treatments were preceded by group education. Methods All participants were on, or at risk of, sick leave due to common mental complaints. Patients were selected for inclusion in this study based on levels of self-reported symptoms ('some' or 'seriously affected') of anxiety and depression. They were randomized to Brief-PsT (n = 141) or Short-PsT with a more extended focus (n = 143). Primary outcome was the transition of WP-state from baseline to 3 months follow-up. In addition, WP at 12 and 24 months follow-up were assessed. The secondary outcome, clinical recovery rate (CR-rate) was obtained from the Beck Depression and Beck Anxiety Inventories, at 2-year follow-up. In addition, self-reported mental health symptom severity, self-efficacy, subjective health complaints and life satisfaction were assessed. Results At 3 months follow-up, the increase in WP was significantly greater in Brief-PsT than in Short-PsT (p = 0.039). At 3 months, 60% in Brief-PsT and 51% in Short-PsT was at work, partial or full. Thereafter, these differences diminished, 84% and 80% were at work at 2-year follow up. The 2-year follow-up of the secondary outcome measurements was completed by 53% in Brief-PsT and 57% in Short PsT. CR-rate was significantly greater in Brief-PsT compared with the Short-PsT (69% vs. 51%, p = 0.024). Furthermore, there was a greater reduction in the number of subjective health complaints in Brief-PsT (4.0 vs. 1.9 p = 0.012). All other measurements favoured Brief-PsT as well, but did not reach statistical significance. Conclusions Brief coping-focused psychotherapy added to group education for persons with depression or anxiety complaints seemed more effective in enhancing early work participation compared with additional short-term psychotherapy of standard duration with more extended focus. Clinical recovery rate and decline of comorbid subjective health complaints at 2-year follow-up were also in favour of the brief coping-focused program.
Subject(s)
Adaptation, Psychological , Anxiety/therapy , Diagnostic Self Evaluation , Mental Disorders/therapy , Personal Satisfaction , Psychotherapy, Brief/methods , Adult , Female , Follow-Up Studies , Humans , Male , Mental Health , Middle Aged , Self Efficacy , Sick Leave , Work EngagementABSTRACT
BACKGROUND: In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. PATIENTS AND METHODS: Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. RESULTS: Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P = 0.006 (P = 0.013 in the validation cohort). CONCLUSION: Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.
Subject(s)
Biomarkers, Tumor/analysis , Models, Biological , Neoplasm Recurrence, Local/epidemiology , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Aged , Biomarkers, Tumor/genetics , Chemoradiotherapy/methods , Cisplatin/therapeutic use , Clinical Decision-Making , Cyclin-Dependent Kinase Inhibitor p16/analysis , DNA, Viral/isolation & purification , Datasets as Topic , Denmark/epidemiology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/prevention & control , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/genetics , Papillomavirus Infections/mortality , Papillomavirus Infections/pathology , Predictive Value of Tests , Prognosis , Risk Assessment/methods , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathologyABSTRACT
Scenario-building is a widely used tool to initiate discussions on future land uses. In scenarios possible futures can be explored and peoples' ideas as well as societal trends can be visualized by the use of maps, pictures and figures. With focus on agricultural nitrogen management, and point of departure in the farmers' decisions-regarding fertilizer inputs, crop rotations, land use, and drainage, landscape scenarios are formulated based on local ideas for future nitrogen management and general prospects for local development. The key research question addressed in this paper is how landscape scenarios can guide farmers to improve nitrogen management in smaller catchments dominated by farming. Participatory modelling was used to develop landscape scenarios, depicting the change of nitrogen emission as a result of changes in landscape management and agricultural practices. In the development of the scenarios we used an ArcMap based tool combining statistical data, experimental knowledge, nitrate leaching modelling and input from local stakeholders on biophysical as well as land use and farm management issues. The scenarios presented are the result of a collaborative planning experiment within the frames of the dNmark research alliance on nitrogen. Three different types of scenarios are presented and discussed and their effects in terms of N reduction are estimated. The three scenarios were called: River valley set-aside, constructed wetlands, and land zonation. All the modelled scenarios are estimated to have a positive effect i.e. a reduction of the level of N leached to the root zone. Based on the experience gathered in the project, the feasibility of using scenarios for future environmental planning in the agricultural landscapes is discussed. Further, this is related to the current discussion in Denmark on geographically targeted nitrogen regulation. It is concluded that the co-creative approach to formulation of scenarios can be an effective way of increasing the knowledge and ownership of possible future solutions, however the cost associated with this planning approach is likely to substantially higher that more traditional planning approaches. Consequently, the estimated transactions costs should be weighed against the expected benefits in terms of more successful implementation.
Subject(s)
Agriculture , Nitrogen , Denmark , Nitrates , RiversABSTRACT
Incidental arterial calcification (Ca) on low-dose computed tomography (CT) prior to liver transplant (LT) may help identify those at risk for obstructive coronary artery disease (CAD). A single-center retrospective study of 358 consecutive patients who had undergone LT was performed. Of the 296 patients who met inclusion criteria, 193 patients (65.2%) had CT Ca. Aortic Ca was seen in 116 (39.2%), coronary Ca in 141 (47.6%), and peripheral Ca in 8 patients (2.7%). Patients with coronary Ca were assigned ordinal coronary artery Ca scores and classified as mild, moderate, and severe. All-cause mortality was higher in patients with Ca in any location (14.5% vs 6.8%, P = .05). Of the patients who underwent coronary angiography, those with obstructive CAD were more likely to have aortic and coronary Ca than patients with nonobstructive or no CAD (85.7% vs 50.0%, P = .02 and 92.9% vs 37.9%, P = < .001, respectively). Severe coronary artery Ca scores were more frequent in patients with obstructive CAD (35.7% vs 0%, P < .001). Any severity coronary Ca had an odds ratio of 11.57 (95% CI, 1.61-244.92; P = .04) for obstructive CAD. In conclusion, incidental coronary Ca seen on low-dose CT is a risk factor for obstructive CAD in patients undergoing LT.
Subject(s)
Calcinosis/complications , Calcinosis/diagnostic imaging , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Liver Transplantation , Aged , Calcinosis/mortality , Coronary Angiography/methods , Coronary Artery Disease/mortality , Female , Humans , Liver Transplantation/mortality , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed/methodsABSTRACT
AIMS: The distinct difference in disease phenotype of human papillomavirus-positive (HPV+) and -negative (HPV-) oropharyngeal squamous cell cancer (OPSCC) patients might also be apparent when assessing the effect of time to treatment initiation (TTI). We assessed the overall survival and progression-free survival (PFS) effect from increasing TTI for HPV+ and HPV- OPSCC patients. MATERIALS AND METHODS: We examined patients who received curative-intended therapy for OPSCC in eastern Denmark between 2000 and 2014. TTI was the number of days from diagnosis to the initiation of curative treatment. Overall survival and PFS were measured from the start of treatment and estimated with the Kaplan-Meier estimator. Hazard ratios and 95% confidence intervals were estimated with Cox proportional hazard regression. RESULTS: At a median follow-up of 3.6 years (interquartile range 1.86-6.07 years), 1177 patients were included (59% HPV+). In the adjusted analysis for the HPV+ and HPV- patient population, TTI influenced overall survival and PFS, most evident in the HPV- group, where TTI >60 days statistically significantly influenced overall survival but not PFS (overall survival: hazard ratio 1.60; 95% confidence interval 1.04-2.45; PFS: hazard ratio 1.46; 95% confidence interval 0.96-2.22). For patients with a TTI >60 days in the HPV+ group, TTI affected overall survival and PFS similarly, with slightly lower hazard ratio estimates of 1.44 (95% confidence interval 0.83-2.51) and 1.15 (95% confidence interval 0.70-1.88), respectively. CONCLUSION: For patients treated for a HPV+ or HPV- OPSCC, TTI affects outcome, with the strongest effect for overall survival among HPV- patients. Reducing TTI is an important tool to improve the prognosis.
Subject(s)
Carcinoma, Squamous Cell/therapy , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/therapy , Carcinoma, Squamous Cell/pathology , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/pathology , Prognosis , Time-to-TreatmentABSTRACT
BACKGROUND: EuroFIT is a gender-sensitised, health and lifestyle program targeting physical activity, sedentary time and dietary behaviours in men. The delivery of the program in football clubs, led by the clubs' community coaches, is designed to both attract and engage men in lifestyle change through an interest in football or loyalty to the club they support. The EuroFIT program will be evaluated in a multicentre pragmatic randomised controlled trial (RCT), for which ~1000 overweight men, aged 30-65 years, will be recruited in 15 top professional football clubs in the Netherlands, Norway, Portugal and the UK. The process evaluation is designed to investigate how implementation within the RCT is achieved in the various football clubs and countries and the processes through which EuroFIT affects outcomes. METHODS: This mixed methods evaluation is guided by the Medical Research Council (MRC) guidance for conducting process evaluations of complex interventions. Data will be collected in the intervention arm of the EuroFIT trial through: participant questionnaires (n = 500); attendance sheets and coach logs (n = 360); observations of sessions (n = 30); coach questionnaires (n = 30); usage logs from a novel device for self-monitoring physical activity and non-sedentary behaviour (SitFIT); an app-based game to promote social support for physical activity outside program sessions (MatchFIT); interviews with coaches (n = 15); football club representatives (n = 15); and focus groups with participants (n = 30). Written standard operating procedures are used to ensure quality and consistency in data collection and analysis across the participating countries. Data will be analysed thematically within datasets and overall synthesis of findings will address the processes through which the program is implemented in various countries and clubs and through which it affects outcomes, with careful attention to the context of the football club. DISCUSSION: The process evaluation will provide a comprehensive account of what was necessary to implement the EuroFIT program in professional football clubs within a trial setting and how outcomes were affected by the program. This will allow us to re-appraise the program's conceptual base, optimise the program for post-trial implementation and roll out, and offer suggestions for the development and implementation of future initiatives to promote health and wellbeing through professional sports clubs. TRIAL REGISTRATION: ISRCTN81935608 . Registered on 16 June 2015.
Subject(s)
Healthy Lifestyle , Overweight/therapy , Self Care , Soccer , Adult , Aged , Diet, Healthy , Europe , Exercise , Focus Groups , Health Behavior , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Mobile Applications , Overweight/diagnosis , Overweight/physiopathology , Overweight/psychology , Patient Education as Topic , Process Assessment, Health Care , Research Design , Sedentary Behavior , Social Support , Surveys and Questionnaires , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic-like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long-term outcome of a series of children with AFM. METHODS: This was a retrospective cohort study. RESULTS: Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain (n = 7) followed by limb weakness with hypotonia (n = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow-up was 28 months (range 17-108 months, 30.4 patient years in total). CONCLUSIONS: Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long-term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.
Subject(s)
Myelitis/diagnosis , Paralysis/diagnosis , Spinal Cord/diagnostic imaging , Child , Child, Preschool , Electrodiagnosis , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Myelitis/diagnostic imaging , Myelitis/pathology , Neural Conduction/physiology , Paralysis/diagnostic imaging , Paralysis/pathology , Retrospective Studies , Spinal Cord/pathologyABSTRACT
Transposons are mobile DNA elements that generate both adaptive and deleterious phenotypic variation thereby driving genome evolution. For these reasons, genomes have mechanisms to regulate transposable element (TE) activity. Approximately 12-16% of the Caenorhabditis elegans genome is composed of TEs, of which the majority are likely inactive. However, most studies of TE activity have been conducted in the laboratory strain N2, which limits our knowledge of the effects of these mobile elements across natural populations. We analyzed the distribution and abundance of TEs in 208 wild C. elegans strains to better understand how transposons contribute to variation in natural populations. We identified 3,397 TEs as compared with the reference strain, of which 2,771 are novel insertions and 241 are TEs that have been excised in at least one wild strain. Likely because of their hypothesized deleterious effects, we find that TEs are found at low allele frequencies throughout the population, and we predict functional effects of TE insertions. The abundances of TEs reflect their activities, and these data allowed us to perform both genome-wide association mappings and rare variant correlations to reveal several candidate genes that impact TE regulation, including small regulatory piwi-interacting RNAs and chromatin factors. Because TE variation in natural populations could underlie phenotypic variation for organismal and behavioral traits, the transposons that we identified and their regulatory mechanisms can be used in future studies to explore the genomics of complex traits and evolutionary changes.
Subject(s)
Caenorhabditis elegans/genetics , DNA Transposable Elements/genetics , Alleles , Animals , Evolution, Molecular , Gene Frequency/genetics , Genetic Variation/genetics , Genome-Wide Association Study , GenomicsABSTRACT
OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142 patients in eastern Denmark undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival and prognostic factors for these outcomes. RESULTS: 5-year overall survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease-specific survival and disease-free survival. Residual tumour/recurrence was negatively associated with overall survival, close or involved resection margins with disease-specific survival, and second primary cancer was associated with longer disease-specific survival and disease-free survival. Nine per cent of all patients had residual tumour and 33.8% developed a recurrence. CONCLUSION: Our overall survival, disease-specific survival and disease-free survival findings are in accordance with previous studies. With the purpose of identifying recurrent tumour, we suggest extra attention being given to patients with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.
Subject(s)
Carcinoma, Squamous Cell/surgery , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Salvage Therapy , Aged , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Denmark , Female , Humans , Laryngeal Neoplasms/therapy , Longitudinal Studies , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Treatment FailureABSTRACT
We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß1 and -ß3, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least partially due to the low temperature of about 8.5 °C during the first 100 days. The inflammation phase lasted more than 14 days, and the genes relating to production and remodeling of new extracellular matrix (ECM) exhibited a delayed but prolonged upregulation starting 1-2 weeks post-wounding and lasting until at least 100 days post-wounding. The gene expression patterns and histology reveal limited capacity for muscle regeneration in rainbow trout, and muscle texture analyses one year after wound infliction confirm that wounds heal with fibrosis. At 100 dpw epidermis had fully regenerated, and dermis partially regenerated. Scales had not regenerated even after one year. CD163 is a marker of "wound healing"-type M2c macrophages in mammals. M2 macrophage markers are as yet poorly described in fish. The pattern of CD163 expression in the present study is consistent with the expected timing of presence of M2c macrophages in the wound. CD163 may thus potentially prove a valuable marker of M2 macrophages - or a subset hereof - in fish. We subjected a group of fish to bathing in an immunomodulatory ß-glucan product during wound healing, but found this to have very limited effect on wound healing in contrast to a previously published study on common carp.
Subject(s)
Muscles , Oncorhynchus mykiss , Wound Healing , Animals , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/immunology , Female , Fibrosis , Fish Proteins/genetics , Fish Proteins/immunology , Gene Expression , Macrophages/immunology , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 9/genetics , Muscles/immunology , Muscles/pathology , Muscles/physiology , Nitric Oxide Synthase Type II/immunology , Oncorhynchus mykiss/immunology , Oncorhynchus mykiss/physiology , Prolyl Hydroxylases/genetics , Protein-Lysine 6-Oxidase/genetics , Receptors, Cell Surface/immunology , Transforming Growth Factor beta1/genetics , Wound Healing/genetics , Wound Healing/immunologyABSTRACT
BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type. CONCLUSIONS: The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010.
Subject(s)
Alphapapillomavirus/isolation & purification , Tongue Neoplasms/epidemiology , Alphapapillomavirus/genetics , Denmark/epidemiology , Humans , Incidence , Tongue Neoplasms/virologyABSTRACT
OBJECTIVES: To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 143 patients undergoing total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: Overall postoperative complications and fistula formation. RESULTS: Overall postoperative complications, fistula formation, wound infection, bleeding and wound necrosis within one year after total laryngectomy occurred in 56.6%, 42.3%, 31.0%, 11.3% and 9.2% of patients, respectively. Stenosis of the pharynx/oesophagus and stoma shrinkage within five years after surgery were each seen in 18.2% of cases. In 66.7% of cases, conservative treatment of the fistulas was chosen. Rehospitalisations within five years occurred for 44.8% with a median rate of 1.5 (range 1-11). Smoking status (P = 0.005 and 0.013) and chronic obstructive pulmonary disease (COPD) (P = 0.013 and 0.011) were significant risk factors for both overall postoperative complications and fistula formation in uni- and multivariate analysis. Tumour localisation in the hypopharynx was associated with overall postoperative complications (P = 0.036). Residual tumour or cancer recurrence was associated with late-onset fistulas (P < 0.001). CONCLUSION: The frequencies of postoperative complications after total laryngectomy were comparable with similar international studies, although fistula formation rate is increasing in Denmark. We suggest optimising treatment of COPD and to further encourage to smoking cessation. We propose that development of fistulas >2 months after surgery prompts immediate biopsies. Additionally, we suggest standardised registration of surgical techniques to identify variables affecting the frequency of postoperative complications.
Subject(s)
Carcinoma, Squamous Cell/therapy , Forecasting , Laryngeal Neoplasms/therapy , Laryngectomy/methods , Postoperative Complications/epidemiology , Risk Assessment , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/epidemiology , Chemoradiotherapy , Denmark/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Laryngeal Neoplasms/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate/trendsABSTRACT
The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all-type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age- and sex-matched population-based comparison cohort of individuals (n = 26,070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all-type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all-type cancer among HBV-infected patients was 1.1 (95% confidence intervals (CI) 0.9-1.3). The IRR of HCC was 17.4 (CI 5.5-54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3-2.5) and 1.2 (CI 0.4-3.6), respectively. HBV-infected patients had a 10-year risk of 0.24% (Cl 0.12-0.44) for HCC, whereas the comparison cohort had a 10-year risk of 0.03% (Cl 0.02-0.07) for HCC. The risk of all-type cancer, NHL and PC was not higher in the HBV-infected cohort compared to non-HBV infected. We found a 17-fold higher risk of HCC for HBV-infected individuals.
Subject(s)
Hepatitis B/complications , Liver Neoplasms/epidemiology , Lymphoma, Non-Hodgkin/epidemiology , Pancreatic Neoplasms/epidemiology , Adolescent , Adult , Cohort Studies , Denmark/epidemiology , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Risk Assessment , Young AdultABSTRACT
Macrophages regulate the fibrotic process in chronic liver disease. The aim of the present pilot study was to evaluate two new macrophage-specific serum biomarkers [soluble CD163 (sCD163) and soluble mannose receptor (sMR, sCD206)] as potential fibrosis markers in patients chronically infected with hepatitis C virus (HCV). Forty patients with chronic hepatitis C were included from two hospital clinics. On the day of inclusion, transient elastography (TE) was performed to assess the fibrosis stage, and blood samples were collected for the measurement of sCD163 and sMR. The plasma concentrations of both biomarkers were significantly higher in patients infected with HCV and with cirrhosis compared to those with no/mild liver fibrosis (5.77 mg/l vs. 2.49 mg/l and 0.44 mg/l vs. 0.30 mg/l for sCD163 and sMR, respectively). The best separation between groups was obtained by sCD163 [area under the receiver operating characteristic curve (AUC) 0.89 (95 % confidence interval [CI] 0.79-0.99)] as compared to sMR [AUC 0.75 (95 % CI 0.61-0.90)]. sCD163 and sMR correlated significantly (r (2) = 0.53, p < 0.0001). Interestingly, sCD163 also correlated significantly with TNF-α (presented in a previous publication), which is shed to serum by the same mechanism as sCD163 (r (2) = 0.40, p < 0.0001). In conclusion, the macrophage-related markers sCD163 and sMR are significantly higher in patients chronically infected with HCV and with cirrhosis than in those with no/mild fibrosis. sCD163 is a promising new fibrosis marker in patients infected with HCV.
Subject(s)
Antigens, CD/blood , Antigens, Differentiation, Myelomonocytic/blood , Biomarkers/blood , Hepatitis C, Chronic/complications , Lectins, C-Type/blood , Liver Cirrhosis/diagnosis , Macrophages/physiology , Mannose-Binding Lectins/blood , Receptors, Cell Surface/blood , Adult , Elasticity Imaging Techniques , Female , Humans , Liver/pathology , Male , Mannose Receptor , Middle Aged , Serum/chemistryABSTRACT
Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (P<0.001). No significant changes were seen with regard to food satisfaction and plate waste. In the control canteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out.