174 research outputs found
Effect of bupivacaine lozenges on oral mucositis pain:a randomized controlled multicenter phase II study
Abstract. Introduction:. A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management.
Objective:. The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher).
Method:. Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data.
Results:. Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups â16 mm, 95% confidence interval: â26 to â6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported.
Conclusion:. These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis.
ClinicalTrials.gov:. NCT02252926
A novel lozenge containing bupivacaine as topical alleviation of oral mucositis pain in patients with head and neck cancer:a pilot study
Abstract. Introduction: Oral mucositis induces severe oral pain in head and neck cancer patients. There is at this point no effective pain treatment without considerable side effects.
Objective: The aim of this pilot study was to investigate pain reduction in oral cavity and pharynx in patients with head and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge.
Methods: Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral cavity and pharynx on a visual analogue scale (from 0 to 100 mm) at baseline and up to 3 hours after the lozenge was dissolved. Possible adverse events were registered.
Results: The baseline pain was 51 mm (range: 30â73 mm) in the oral cavity and 58 mm (range: 35â70 mm) in the pharynx. When the lozenge was dissolved, both oral (â27 mm; range: â3 to â52 mm; P = 0.0003) and pharynx pain (â20 mm; range: â3 to â45 mm; P = 0.008) were significantly reduced. After 180 minutes, the mean reduction in pain was significant in the oral cavity (â18 mm; range: â8 to â30 mm; P < 0.0001) but not in the pharynx (â8 mm; range: +4 to â23 mm; P = 0.12). No adverse events were observed.
Conclusion: The results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC
Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer
AbstractBackground and purposeHPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage IIIâIV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin.Material and methods1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells.ResultsThirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p<.0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR [95% CI]: 0.43 [0.32â0.57]), event-free survival (EFS) (HR 0.44 [0.35â0.56]), and overall survival (OS) (HR: 0.38 [0.29â0.49]), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 [0.75â1.70]), EFS (HR: 1.06 [0.76â1.47]), and OS (HR: 0.82 [0.59â1.16]).ConclusionsThe independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only
Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads
Abstract The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC). SRY/SOX9 expression initiated in testis around day 40âpc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53âpc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human sex-differentiation is defined, with identification of new genes of potential importance
A revised lithostratigraphy for the Palaeogene â lower Neogene of the Danish North Sea
Intense drilling activity following the discovery of the Siri Field in 1995 has resulted in an improved understanding of the siliciclastic Palaeogene succession in the Danish North Sea sector (Fig. 1). Many of the new wells were drilled in the search for oil reservoirs in sand bodies of PaleoceneâEocene age. The existing lithostratigraphy was based on data from a generation of wells that were drilled with deeper stratigraphic targets, with little or no interest in the overlying Palaeogene sediments, and thus did not adequately consider the significance of the Palaeogene sandstone units in the Danish sector. In order to improve the understanding of the distribution, morphology and age of the Palaeogene sediments, in particular the economically important sandstone bodies, a detailed study of this succession in the Danish North Sea has recently been undertaken. An important aim of the project was to update the lithostratigraphic framework on the basis of the new data. The project was carried out at the Geological Survey of Denmark and Greenland (GEUS) with participants from the University of Aarhus, DONG E&P and Statoil Norway, and was supported by the Danish Energy Agency. Most scientific results cannot be released until September 2006, but a revised lithostratigraphic scheme may be published prior to that date. Formal definition of new units and revision of the lithostratigraphy are in preparation. All of the widespread Palaeogene mudstone units in the North Sea have previously been formally established in Norwegian or British wells, and no reference sections exist in the Danish sector. As the lithology of a stratigraphic unit may vary slightly from one area to another, Danish reference wells have been identified during the present project, and the lithological descriptions of the formations have been expanded to include the appearance of the units in the Danish sector. Many of the sandstone bodies recently discovered in the Danish sector have a limited spatial distribution and were sourced from other areas than their contemporaneous counterparts in the Norwegian and British sectors. These sandstone bodies are therefore defined as new lithostratigraphic units in the Danish sector, and are assigned Danish type and reference sections. There is a high degree of lithological similarity between the PalaeogeneâNeogene mudstone succession from Danish offshore boreholes and that from onshore exposures and boreholes, and some of the mudstone units indeed seem identical. However, in order to acknowledge the traditional distinction between offshore and onshore stratigraphic nomenclature, the two sets of nomenclature are kept separate herein. In recent years oil companies operating in the North Sea have developed various in-house lithostratigraphic charts for the PaleoceneâEocene sand and mudstone successions in the Danish and Norwegian sectors. A number of informal lithostratigraphic units have been adopted and widely used. In the present project, these units have been formally defined and described, maintaining their original names whenever feasible, with the aim of providing an unequivocal nomenclature for the Palaeogene â lower Neogene succession in the Danish sector. It has not been the intention to establish a sequence stratigraphic model for this succession in the North Sea; the reader is referred to the comprehensive works of Michelsen (1993), Neal et al. (1994), Mudge & Bujak (1994, 1996a, b), Michelsen et al. (1995, 1998), Danielsen et al. (1997) and Rasmussen (2004)
Precipitation of Trichoderma reesei commercial cellulase preparations under standard enzymatic hydrolysis conditions for lignocelluloses
Comparative studies between commercial Trichoderma reesei cellulase preparations show that, depending on the preparation and loading, total protein precipitation can be as high as 30 % under standard hydrolysis conditions used for lignocellulosic materials. ATR-IR and SDS-PAGE data verify precipitates are protein-based and contain key cell wall hydrolyzing enzymes. Precipitation increased considerably with incubation temperature; roughly 50â150 % increase from 40 to 50 °C and 800 % greater at 60 °C. All of the reported protein losses translated into significant, and often drastic, losses in activity on related 4-nitrophenyl substrates. In addition, supplementation with the non-ionic surfactant PEG 6,000 decreased precipitation up to 80 % in 24 h precipitation levels. Protein precipitation is potentially substantial during enzymatic hydrolysis of lignocelluloses and should be accounted for during lignocellulose conversion process design, particularly when enzyme recycling is considered.This work was supported by the project "Demonstrating Industrial scale second generation bioethaol production-Kalundborg Cellulosic Ethanol Plant" under the EU FP7 framework program and the project "Development of improved second generation (2G) bioethanol technology to prepare for commercialization under the Danish Energy Technology and Demonstration Programme (EUDP)
Exploring international differences in ovarian cancer treatment: A comparison of clinical practice guidelines and patterns of care
BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers
Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers.
Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.
Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptorânegative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed.
Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations
SARS-CoV-2 antibody prevalence among homeless people and shelter workers in Denmark:a nationwide cross-sectional study
BACKGROUND: People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with âSevere acute respiratory syndrome coronavirus 2â (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. DESIGN AND METHODS: In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. RESULTS: We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9â59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1â55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, pâ=â0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, pâ<â0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (OR 2.23, 95%CI 1.06â4.43, pâ=â0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). INTERPRETATIONS: The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. These results could be taken into consideration when deciding in which phase PEH are eligible for a vaccine, as part of the Danish national SARS-CoV-2 vaccination program rollout. FUNDING: TrygFonden and HelseFonden. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13642-7
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