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  • Oxford University Press (OUP)  (67)
  • English  (67)
  • 1
    In: Rheumatology, Oxford University Press (OUP), Vol. 63, No. Supplement_1 ( 2024-04-24)
    Abstract: Proton Pump Inhibitors (PPIs) are widely used in Systemic Sclerosis (SSc) for the treatment of gastroesophageal reflux disease (GERD). However, there is scarce evidence to support their use while long-term safety has been questioned. The aim of our study was to identify healthcare providers’ perspectives and experience regarding PPIs therapy in SSc patients. Methods An online survey in English language targeting clinicians involved in the care of SSc patients, was developed and distributed through social media and international physician networks. The survey was launched on 27th November 2022 and kept open for three weeks. Results Responses from 227 clinicians from 36 countries were recorded: most of them (86%) were between 30-70 years and gender was equally represented (F: 52%; M: 48%). The majority ‘agreed’ (41%) or ‘strongly agreed’ (45%) that GERD is a major cause of morbidity in SSc. Lifestyle modifications and non-pharmacological approaches alone were seldom (16%) considered effective. Only half of respondents ‘agreed’ (43%) or ‘strongly agreed’ (11%) there is solid evidence supporting PPIs efficacy in SSc. A range of PPIs was prescribed by clinicians, most frequently pantoprazole (74%), esomeprazole (72%), omeprazole (72%), and lansoprazole (68%). The most common reasons for PPIs prescription (Table 1) were symptomatic GERD unresponsive to lifestyle modification (95%), objective evidence of GERD (82%), and hoarseness or respiratory symptoms (71%). Multiple concerns were raised about PPI long-term safety. The three highest (mean, 10 being very concerned) reasons were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There were significant differences in attitudes towards surgery for refractory GERD: ‘strongly disagreed’ (14%), ‘disagreed’ (26%) ‘neutral’ (52%), ‘agreed’ (13%), ‘strongly agreed’ (3%). Furthermore, half of respondents had concerns about potential complications (i.e., worsening of dysphagia): ‘disagreed’ (26%) or ‘strongly disagreed’ (6%), ‘neutral (52%), ‘agreed’ (13%), ‘strongly agreed’ (3%). Conclusion Our survey confirms that PPIs are frequently prescribed for GERD in SSc patients, despite the absence of randomized clinical trials demonstrating their efficacy and safety. Clinicians are concerned about side effects, especially regarding long-term use. There is significant heterogeneity in attitudes towards surgery for refractory GERD. Future research and practical treatment recommendation are urgently needed. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 2
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: In Systemic Sclerosis (SSc), gastroesophageal reflux disease (GERD) occurs in 75% of patients. Chronic doses of proton pump inhibitors may elicit in the general population long-term risk. When medical therapy fails, surgery can be employed but consensus on surgical procedures for refractory GERD is still lacking in SSc. Our aim was to evaluate the surgical approaches employed in the management of refractory GERD with a systematic literature research (SLR). Four research questions, based on the PICO framework, guided the SLR which was conducted up to December 22nd, 2021. The search was performed across different databases including PubMed, MEDLINE (OVID), EMBASE, Cochrane Library, Web of Science, Google Scholar, Emcare and Academic Search Premier. References were independently screened by two reviewers (PMC and AA) who also independently assessed the full text of eligible articles, and extracted data. Due to heterogeneity of retrieved studies, narrative summaries are used to present the data. In 30/916 papers, eligible for review, 348 patients were identified: 257 underwent an anti-reflux surgical procedure and included in the analysis. Refractory GERD was the most frequent indication for surgery, and post-operative dysphagia was a frequent complication. In 18 studies, fundoplication (FP) was effective, whereas 4 studies had equivocal findings and 5 didn’t report efficacy. Surgical procedures have changed in time: overall, the Collis-Nissen FP was the most popular in old studies, followed by Nissen FP, while Dor FP has been used more recently. The data extracted show also an acceptable rate of mortality and morbidity related to surgery. In SSc, FP seems a safe and effective procedure for GERD management. In many studies, transient post-operative dysphagia was related with the posterior FP. Our SLR shows that the surgical management of GERD is still highly challenging and minimal requirements should be provided to perform surgical studies in SSc, designing studies to define clinical criteria for surgical referral. In SSc, the right timing for surgery and the best surgical procedure still remain an unmet need.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
    In: Rheumatology, Oxford University Press (OUP), Vol. 63, No. Supplement_1 ( 2024-04-24)
    Abstract: The gastrointestinal (GI) tract is largely ( & gt;95%) affected in systemic sclerosis (SSc) and its involvement is associated with significant morbidity, mortality and huge impact on the quality of life. Upper GI tract dysfunction, often presenting with gastroesophageal reflux disease (GERD) is one of the principal complaints. Proton pump inhibitors (PPIs) are widely used to treat GERD in SSc. However, not all patients respond to this therapy, and many remain on long-term treatment. Significant concerns about PPI long-term safety have been raised. Our aim was to identify perspectives and unmet needs of SSc patients on PPIs. Methods An online English survey, targeting SSc patients on PPIs was developed and distributed through social media and international patient associations. The survey was launched on 4th November 2022 and kept open for 4 weeks. Results 301 respondents from 14 countries completed the survey (UK 19.3% and US 70.4%). Most respondents were between 30-70 years and the majority were female (95%). The most frequently reported symptoms were acid reflux (97%), dysphagia (60%), and trouble swallowing or food got stuck in the chest (32%). Multiple PPIs use (two: 30% and three: 21%; in series) was common and the majority (89%) reported improvement in GI symptoms with PPIs. Even though only 19% experienced side effects on PPIs, most respondents (79%) were concerned (Table 1). Half (47%) experienced a flare of symptoms after initial improvement with PPIs and 58% received lifestyle information, while most (85%) searched online for information about PPIs. A minority (12%) reported that a surgical approach was discussed, and 46% indicated that they would be willing to undergo surgery, despite having significant concerns. Conclusion Our survey highlights the importance of upper GI symptoms in SSc patients and the frequent use of PPIs. There is significant heterogeneity in use, and treatment is often not fully effective. Patients have concerns about side effects related to long-term PPI use. There is a clear unmet need regarding patients’ education about PPIs. A surgical approach is rarely discussed, although patients would potentially consider this approach. Further research is needed to optimize the therapeutic strategy concerning PPIs in SSc. Disclosure G. Bandini: None. A. Alunno: None. F. Oliveira Pinheiro: None. C. Campochiaro: None. I. Galetti: None. P. Matucci Cerinic: None. B. Ruaro: None. K. El Aoufy: None. M. Melis: None. A. Moggi Pignone: None. L. Dagna: None. M. Matucci Cerinic: None. Z. McMahan: None. M. Hughes: None.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 4
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 4 ( 2022-04-11), p. 1600-1609
    Abstract: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. Methods This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Results Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P & lt; 0.0001) and signs of fibrosis in GGOs in the lower lobes (P & lt; 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). Conclusion CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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    detail.hit.zdb_id: 1474143-X
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  • 5
    In: Rheumatology, Oxford University Press (OUP), Vol. 55, No. 10 ( 2016-10), p. 1826-1836
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 6
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 111, No. 1 ( 2024-01-03)
    Abstract: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures. Methods This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge. Results The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1–30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80–100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P & lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (β coefficient 0.92, 95% c.i. −1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not. Conclusion Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 7
    In: Rheumatology, Oxford University Press (OUP), ( 2024-05-15)
    Abstract: To report real-life data on rituximab retention rate as an indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. Methods SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized and longitudinally monitored. A competing risk analysis with sub-hazard ratio (sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. Results One-hundred and fifty-two SSc-patients [mean age 47.3 (12.3) years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%] were evaluated over a median (interquartile range) time of 3.3 (1.7–5.0) years. The primary indications for rituximab were interstitial lung disease (38.8%), worsening skin fibrosis (36.8%) and arthritis (13.8%); 138 patients (90.8%) received more than one rituximab course. The 5-year rituximab retention rate was 59.9% (44.6–64.7%). Clinical response was the most common reason for rituximab discontinuation [5.7; 95% CI: (3.7–8.4) per 100 patient-years] and was associated with a shorter disease duration (sHR 0.8; 95% CI: 0.7, 0.9), anti-topoisomerase-I negativity (sHR 0.4; 95% CI: 0.2, 0.9), previous digital ulcers (sHR 2.6; 95% CI: 1.1, 6.2) and no history of arthritis (sHR 0.3; 95% CI: 0.1, 0.8). Treatment failure was the second cause of rituximab discontinuation [3.7 (95% CI: 2.2, 6.0) per 100 patient-years] and was associated with anti-centromere antibody positivity (sHR 2.8; 95% CI: 1.1, 7.4) and anti-topoisomerase-I negativity (sHR 0.2; 95% CI: 0.1, 0.6). Adverse events (AEs) were the less common cause of discontinuation [3.1 (95% CI: 1.7, 5.2) per 100 patient-years] , associated with limited cutaneous subset (sHR 3.4; 95% CI: 1.2, 9.7) and previous mycophenolate mofetil treatment (sHR 4.5; 95% CI: 1.2, 16.3). Conclusion Rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 8
    In: Rheumatology, Oxford University Press (OUP), ( 2023-12-22)
    Abstract: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. Methods Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. Results The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu’s arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet’s disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan’s syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). Conclusion In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1464822-2
    detail.hit.zdb_id: 1474143-X
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  • 9
    In: Rheumatology, Oxford University Press (OUP), Vol. 63, No. 1 ( 2024-01-04), p. 226-234
    Abstract: We characterized the microbiota in SSc, focusing on the skin–oral–gut axis and the serum and faecal free fatty acid (FFA) profile. Methods Twenty-five SSc patients with ACA or anti-Scl70 autoantibodies were enrolled. The microbiota of faecal, saliva and superficial epidermal samples was assessed through next-generation sequencing analysis. GC-MS was used to quantify faecal and serum FFAs. Gastrointestinal symptoms were investigated with the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (UCLA GIT-2.0) questionnaire. Results The ACA+ and anti-Scl70+ groups displayed different cutaneous and faecal microbiota profiles. The classes of cutaneous Sphingobacteriia and Alphaproteobacteria, the faecal phylum Lentisphaerae, the levels of the classes Lentisphaeria and Opitutae, and the genus NA-Acidaminococcaceae were significantly higher in faecal samples from the ACA+ patients than in samples from the anti-Scl70+ patients. The cutaneous Sphingobacteria and the faecal Lentisphaerae were significantly correlated (rho = 0.42; P = 0.03). A significant increase in faecal propionic acid was observed in ACA+ patients. Moreover, all levels of faecal medium-chain FFAs and hexanoic acids were significantly higher in the ACA+ group than in the anti-Scl70+ group (P  & lt; 0.05 and P  & lt; 0.001, respectively). In the ACA+ group, the analysis of the serum FFA levels showed an increasing trend in valeric acid. Conclusion Different microbiota signatures and FFA profiles were found for the two groups of patients. Despite being in different body districts, the cutaneous Sphingobacteria and faecal Lentisphaerae appear interdependent.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1464822-2
    detail.hit.zdb_id: 1474143-X
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  • 10
    In: Journal of Bone and Mineral Research, Oxford University Press (OUP), Vol. 19, No. 6 ( 2004-06-01), p. 1013-1017
    Abstract: PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. Introduction: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. Materials and Methods: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. Results: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. Conclusions: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
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    detail.hit.zdb_id: 632783-7
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