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- Jakubowska, A, et al.
(författare)
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Association of PHB 1630 C andgt; T and MTHFR 677 C andgt; T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study
- 2012
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Ingår i: British Journal of Cancer. - : Cancer Research UK / Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:12, s. 2016-2024
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. less thanbrgreater than less thanbrgreater thanMETHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 Candgt;T (rs6917) polymorphism and the MTHFR 677 Candgt;T (rs1801133) polymorphism, respectively. less thanbrgreater than less thanbrgreater thanRESULTS: There was no evidence of association between the PHB 1630 Candgt;T and MTHFR 677 Candgt;T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 Candgt;T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. less thanbrgreater than less thanbrgreater thanCONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.
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- Bergqvist, Joel, et al.
(författare)
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Non-infectious rhinitis is more strongly associated with early-rather than late-onset of COPD: data from the European Community Respiratory Health Survey (ECRHS)
- 2020
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 277, s. 1353-1359
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC < 0.7. A total of 5901 subjects were included. Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54). In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III. Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.
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- Bove, Mogens, 1949, et al.
(författare)
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The pharyngeal mucosa is not involved in eosinophilic oesophagitis.
- 2009
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 30:5, s. 495-500
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Eosinophilic oesophagitis is thought to be an isolated oesophageal disease associated with biopsy-verified eosinophilia of the squamous cell epithelium of the oesophagus. Food- or aeroallergens have been suggested to be the cause of eosinophilic oesophagitis; however, as these allergens pass through the pharynx sharing the same squamous cell epithelium, eosinophilic infiltration could be expected also here. Whether this is true or not has hitherto not been clarified. AIM: To find out whether eosinophilia is present also within the pharyngeal epithelium in patients with eosinophilic oesophagitis. METHODS: In all, 10 patients (median age 34, range 15-70) with biopsy-verified eosinophilic oesophagitis [peak count >20 eosinophils per high power field (hpf)] were biopsied also in the pharynx. The biopsies underwent histopathological examination and at each level, the peak number of eosinophils per hpf was counted. RESULTS: None of the patients examined was found to have eosinophilia within the squamous cell epithelium of the pharynx (median peak count 0, range 0-1). CONCLUSIONS: The pronounced eosinophilic infiltration in eosinophilic oesophagitis appears to be an isolated oesophageal phenomenon not shared by the adjoining organ sites and in particular, not by the pharynx. This may have implications for future research.
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- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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- Hillert, J., et al.
(författare)
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Expert opinion on the use of contraception in people with multiple sclerosis
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 187-188
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The most appropriate use, type, and timing of contraception in people with multiple sclerosis (PwMS) is poorly understood, and specific guidance is absent.Aims and Objectives: To provide insight into potential clinical guidelines for the use of contraception by PwMS through development of recommendations by a consensus-based program led by international clinical experts.Methods: A multidisciplinary steering committee (SC) of 13 international expert healthcare professionals (HCPs) identified 15 key clinical questions on the use of contraception in PwMS, which addressed issues relating to patient-centred care, selection of contraception for PwMS, and time needed to use contraception since the last dose of disease modifying therapies (DMTs). Twenty-five clinical recommendations addressing the questions were drafted using evidence obtained from a comprehensive systematic literature review combined with expert opinion from the SC. An extended faculty of 32 HCPs from 18 countries including a patient association representative, and the SC members (n=12), voted on the recommendations. Consensus on recommendations was achieved when ⩾75% of respondents expressed an agreement score of 7–9, on a 9-point scale.Results: Overall, consensus was achieved on 24 out of 25 clinical recommendations. In detail, consensus in the range of 90–100% was achieved on 11 recommendations, 12 recommendations achieved 80–89% consensus, and 1 recommendation achieved 75–79% consensus (n=44). The strength of recommendations ranged from 7–9. The one statement failing to achieve consensus scored 74.1%. Clinical recommendations are provided on the process of prescribing contraception for PwMS, including the recommended types of HCPs involved and optimal topics to discuss; the range of contraceptive options and the key considerations involved in selecting an appropriate method of contraception; and the timing of starting and stopping contraception in relation to the use of DMTs.Conclusions: These expert recommendations were based on a robust consensus approach, providing timely and practical guidance on the use of contraception for HCPs treating PwMS and will form the basis of further publications and clinical tools.
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- Hillert, Jan, et al.
(författare)
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Expert opinion on the use of contraception in people with multiple sclerosis
- 2024
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970.
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking.OBJECTIVE: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS).METHODS: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation.RESULTS: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs.CONCLUSION: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.
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| 14. |
- Larsson, Helen, 1982, et al.
(författare)
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Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia.
- 2016
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Ingår i: Diseases of the esophagus. - : Oxford University Press (OUP). - 1120-8694. ; 29:8, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker.
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| 15. |
- Varsani, H, et al.
(författare)
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Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease
- 2015
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:1, s. 204-210
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Tidskriftsartikel (refereegranskat)abstract
- To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity.Methods55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy.ResultsInter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity.ConclusionsThe JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.
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