Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

PubMed Central

Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Marshall, Vickie; Whitby, Denise; Wang, Victoria; Pittaluga, Stefania; O’Mahony, Deirdre; Steinberg, Seth M.; Little, Richard F.; Yarchoan, Robert

2014-01-01

Kaposi sarcoma (KS) herpesvirus–associated multicentric Castleman disease (KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m2 combined with liposomal doxorubicin 20 mg/m2 (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-α, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months’ potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, human interleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222. PMID:25331113

TAFRO syndrome: current perspectives.

PubMed

Sakashita, Kentaro; Murata, Kengo; Takamori, Mikio

2018-01-01

Multicentric Castleman's disease (MCD), a distinct subtype of Castleman's disease, is a rare, nonneoplastic, lymphoproliferative disorder. Patients with MCD present with systemic symptoms and multiple lymphadenopathy. Lymph node biopsy is necessary for the diagnosis of various histological MCD patterns including hyaline vascular, plasma cell, and mixed types. Human herpesvirus 8 (HHV8) infection was identified as an important etiology of MCD among immunocompromised patients such as those positive for human immunodeficiency virus. Although HHV8-negative MCD was reported in immunocompetent patients, the underlying etiology remains unknown. Several experts speculate that MCD in immunocompetent patients might be due to proinflammatory hypercytokinemia because of infection by a virus other than HHV8, inflammation, or neoplastic disease. In 2010, a distinct variant of HHV8-negative MCD reported in Japan was characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Recent case reports and a systematic review suggest that TAFRO syndrome might have a unique pathogenesis among HHV8-negative MCD variants. This review introduces TAFRO syndrome as a subtype of HHV8-negative MCD and offers an overview of the current perspectives on this syndrome.

A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.

PubMed

van Rhee, Frits; Casper, Corey; Voorhees, Peter M; Fayad, Luis E; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

2015-10-06

Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.

Castleman Disease Collaborative Network Biobank

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia; Giant Lymph Node

International Registry for Patients With Castleman Disease

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia, Giant Lymph Node; Lymph Node Hyperplasia, Giant

Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).

PubMed

Chadburn, A; Hyjek, E M; Tam, W; Liu, Y; Rengifo, T; Cesarman, E; Knowles, D M

2008-11-01

Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

TAFRO Syndrome.

PubMed

Igawa, Takuro; Sato, Yasuharu

2018-02-01

TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Carotid body tumor imitator: An interesting case of Castleman's disease.

PubMed

Shakir, Hakeem J; Diletti, Sara M; Hart, Alexandra M; Meyers, Joshua E; Dumont, Travis M; Siddiqui, Adnan H

2015-01-01

There are very few reports in the literature of Castleman's disease affecting the carotid artery and a single previous report of a case of Castleman's disease of the neck originally mistaken as a carotid body tumor. We describe a rare case of Castleman's disease, manifesting with classic radiographic hallmarks of a carotid body tumor. The postoperative pathologic examination identified the resected mass as Castleman's lymphadenopathy. The management of this particular case is discussed, and the findings are highlighted. We present a unique case of a tumor initially and incorrectly diagnosed as a carotid body tumor. However, after comprehensive treatment with endovascular and surgical modalities and subsequent pathologic examination, the diagnosis of this rare entity was made.

Multicentric Castleman's disease associated with IgA vasculitis (Henoch-Schönlein purpura) responding well to tocilizumab: a case report.

PubMed

Oshima, Yoichi; Hoshino, Junichi; Suwabe, Tatsuya; Hayami, Noriko; Yamanouchi, Masayuki; Sekine, Akinari; Ueno, Toshiharu; Mizuno, Hiroki; Yabuuchi, Junko; Imafuku, Aya; Kawada, Masahiro; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Hayashi, Nobukazu; Fujii, Takeshi; Ubara, Yoshifumi

2017-03-01

A 41-year-old man was referred to our hospital for the evaluation of hypergammaglobulinemia (IgG 2898 mg/dL and IgA 587 mg/dL), inflammation (CRP 6.7 mg/dL and serum interleukin-6 (IL-6) 15.1 ng/L), and anemia (Hb 10.9 mg/dL). Castleman's disease (CD) was diagnosed by axillary lymph node biopsy. Five months later, painful purpura (multiple palpable 5 mm lesions) developed on his legs, gradually spreading to the upper limbs, thighs, and trunk, accompanied by arthralgia of the wrists, ankles, and knees. Skin biopsy revealed leukocytoclastic vasculitis with IgA deposits in dermal vessels. Accordingly, IgA vasculitis (Henoch-Schönlein purpura) was diagnosed. Tocilizumab (an anti-IL-6 receptor antibody) was administered intravenously at 8 mg/kg and treatment was repeated at monthly intervals. His purpura and clinical findings specific to CD improved rapidly. CD is well known to cause various skin lesions. The findings in this case indicate that overproduction of IL-6 contributes to IgA vasculitis (Henoch-Schönlein purpura) as well as to the pathogenesis of CD.

[Diagnosis and surgical treatment of Castleman's disease].

PubMed

Ma, Shi-hong; Liu, Qin-jiang; Zhang, You-cheng; Yang, Rong

2011-04-26

To explore the clinical features and surgical treatment of tumors associated with Castleman's disease (CD). The clinical profiles of 19 patients with neck giant lymph node hyperplasia were analyzed retrospectively. There were 8 males and 11 females with a median age of 40 years old (range: 7 - 74). The tumor locations were neck (n = 12), neck & mediastinal cavity (n = 2), axillary fossa (n = 2), retroperitoneal area (n = 2) and abdominal cavity (n = 1). Eighteen of them underwent surgical resection of tumor or lymph nodes. All were diagnosed as CD by pathological examinations. There were 16 localized CD (LCD) including hyaline vascular type (HV type, n = 11), mixed type (mix type, n = 4) and plasma cell type-Hodgkin's disease (n = 1). Among 3 multicentric CD (MCD), there were 2 case of plasma cell type (PC type) and 1 case of mixed type (mix type). Long-term survival was achieved in 19 cases among which 1 case of plasma cell type MCD survived for 5 years and underwent a second operation and postoperative chemotherapy of CVP (cyclophosphamide, vincristine & prednisone) regimen for 3 cycles due to recurrence in 2 years and 1 case of plasma cell type LCD-Hodgkin's disease survived for 15 months and underwent a second operation and postoperative chemotherapy of ABVD (adriamycin, bleomycin, vinblastine & dacarbazine)regimen for 6 cycles due to recurrence in 6 months. One case of plasma cell type MCD in abdominal cavity on chemotherapy of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine & prednisone) regimen for 6 cycles was discharged after a successful management of intestinal obstruction. The major clinical symptom of CD is a gradually enlarging painless mass. Surgical resection of tumor remains the first-line treatment for localized CD and the prognosis is excellent. Multicentric and plasma cell type CDs are prone to recurrence and transformation to lymphoma. And their first-line therapeutic should encompass multi-modality regimens of surgery and adjuvant chemotherapy. However, the clinical prognosis is still poor.

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Clinical characteristics and outcomes of Castleman disease: A multicenter study of 185 Chinese patients.

PubMed

Zhang, Xuanye; Rao, Huilan; Xu, Xiaolu; Li, Zhihua; Liao, Bing; Wu, Hongmei; Li, Mei; Tong, Xiuzhen; Li, Juan; Cai, Qingqing

2018-01-01

Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. One hundred and twenty-one patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%), and mixed type for 3 patients (1.6%). The 5-year overall survival (OS) of 185 CD cases was 80.3%. All UCD patients underwent surgical excision, whereas the treatment strategies of MCD patients were heterogeneous. The outcome for UCD patients was better than MCD patients, with 5-year OS rates of 93.6% and 51.2%, respectively. In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. This multicenter study comprising the largest sample size to date suggested that MCD is a distinct entity from UCD with a significantly worse outcome. Older age (≥40 years), splenomegaly, and hypoalbuminemia were risk factors for poorer MCD prognosis. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Sonographic findings of localized Castleman disease of the abdomen and pelvis.

PubMed

Zhou, Wei; Zhan, Weiwei; Zhou, Jianqiao; Zhu, Ying; Yao, Jiejie

2015-09-01

The purpose of this study was to sonographically evaluate the diagnosis of localized Castleman disease in the abdomen and pelvis. This was a retrospective analysis of 18 cases of Castleman disease localized in the abdomen and pelvis. The following features of the lesions were assessed on sonography (US): location, size, margin, echogenicity, echotexture, intralesional cystic necrosis, intralesional calcification, posterior acoustic enhancement, and blood supply. Of the 18 tumors, 16 were located in the abdomen and 2 were located in the pelvis close to iliac vessels. The most frequent appearance of localized Castleman disease in the abdomen and pelvis on US was of a single, well-defined, hypoechoic solid mass with no intralesional cystic necrosis. The internal echotexture was homogeneous in 4 cases and heterogeneous in 14 cases, with thin hyperechoic septa (n = 14) or calcifications (n = 3). Posterior acoustic enhancement was seen in 17 of the 18 cases (94%). Ninety-four percent of the lesions (17/18) had marked vascularity on color Doppler US. Localized Castleman disease in the abdomen and pelvis usually appears on US as a heterogeneously hypoechoic lesion containing thin septa, and more commonly than not, demonstrates posterior acoustic enhancement and marked vascularity. © 2014 Wiley Periodicals, Inc.

Rare Forms of Castleman Disease Mimicking Malignancy: Mesenteric and Pancreatic Involvement.

PubMed

Ozsoy, Mustafa; Ozsoy, Zehra; Sahin, Suleyman; Arıkan, Yuksel

2018-03-12

Castleman disease is a lymphoproliferative disorder with unknown etiology and pathogenesis. While the disease may involve all parts of the body, the mediastinum appears to be the most common part of involvement. In this study, we present two cases of Castleman disease with different localizations that mimicked malignancy. A 62-year-old female patient presented with jaundice. Laboratory analysis indicated aspartate aminotransferase: 250 U/L, total bilirubin: 4 mg/dl, and carbohydrate antigen (CA) 19-9: 900 U/ml. Computerized tomography (CT) of the abdomen showed a mass originating from the pancreas head which resulted in a biliary tract obstruction. A positron emission tomography-computed tomography (PET/CT) showed that the only site of involvement was the pancreas head. A decision was made to perform pancreaticoduodenectomy. During intra-abdominal exploration, lymphadenopathies were identified in the surroundings of the retropancreatic portal vein and the hepatic artery. Histopathological investigation of the dissected lymph nodes demonstrated findings consistent with granulomatous plasma-cell-rich Castleman disease. A 55-year-old female patient presented with abdominal pain, nausea, and vomiting. Computerized tomography of the abdomen showed an abdominal mass of 7 cm, originating from the mesenterium, with high-contrast uptake in the mesenterium in the lower abdominal quadrant. The mesenteric mass was resected along with segmentary small intestine resection. Histopathological investigation of the mass showed a giant granulomatous structure that consisted of plasma cells consistent with Castleman disease. Castleman disease should be kept in mind during differential diagnosis of locally advanced lymph nodes observed during preoperative investigations and intraoperative exploration.

Castleman Disease Presenting as an Abdominal Mass.

PubMed

Shariati, Farnaz; Verter, Elizabeth; Chang, Wendy; Huang, Li; Joshi, Virendra

2017-01-01

Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease.

Castleman Disease Presenting as an Abdominal Mass

PubMed Central

Verter, Elizabeth; Chang, Wendy; Huang, Li; Joshi, Virendra

2017-01-01

Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease. PMID:28584844

Castleman's Disease: An Interesting Cause of Hematuria.

PubMed

Tolofari, Sotonye Karl; Chow, Wai-Man; Hussain, Basharat

2015-03-01

Castleman's disease is a rare benign lymphoproliferative disorder, characterized by benign growths of the lymph node tissue. It is associated with a number of malignancies, including Kaposi sarcoma, non-Hodgkin's and Hodgkins lymphoma, and POEMS syndrome. This report describes the case of a 38 year old gentleman, presenting with painless hematuria. Initial investigations, including flexible cystoscopy were unremarkable. However, subsequent imaging including CT Urogram and MR pelvis revealed multiple prevesical lesions. Histology obtained from excision biopsy revealed histological features consistent with Castleman's disease. In this report we discuss the nature, presentation and treatment modalities of this rare condition.

Clinical spectrum of Castleman disease-associated neuropathy.

PubMed

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman's disease.

PubMed

Sun, Yu; Wang, Dai; Salvadore, Giacomo; Hsu, Benjamin; Curran, Mark; Casper, Corey; Vermeulen, Jessica; Kent, Justine M; Singh, Jaskaran; Drevets, Wayne C; Wittenberg, Gayle M; Chen, Guang

2017-11-01

Cytokines, including interleukin-6 (IL-6), modulate neuronal plasticity and stress coping. Depressive symptoms and major depressive disorder (MDD) have been associated with changes in cytokines and their signaling. The current study examined the effect of IL-6 monoclonal antibody administration on depressive symptoms in patients with rheumatoid arthritis (RA) or multicentric Castleman's disease (MCD). The data were obtained from two phase 2, double-blind, placebo-controlled trials designed to test the efficacy of sirukumab in RA (N=176) or of siltuximab in MCD (N=65), and were analyzed post hoc to investigate the effects of these IL-6 antibodies on depressive symptoms. The SF-36 questionnaire items on depressed-mood and anhedonia were combined as the measure for depressive symptoms. The study participants were grouped by the presence/absence of prevalent depressed mood and anhedonia (PDMA, meaning either depressed mood or anhedonia was present at least 'most of the time' and the other at least 'some of the time' for four weeks) at baseline; 26.1% of the RA sample and 15.4% of the MCD sample met criteria for PDMA at baseline. Compared with placebo, sirukumab and siltuximab produced significantly greater improvements on depressive symptoms. To account for an effect on mood due to changes in RA or MCD, the analysis was (1) adjusted for symptom severities using DAS28-CRP for RA and MCDOS for MCD alone or together with bodily pain and physical functioning, and (2) performed within RA and MCD non-responders. Improvement in depressive symptoms remained significant in the treated group for both drugs. The significance over placebo was also observed in the siltuximab study. The improvement in depressive symptoms by sirukumab correlated positively with the baseline soluble IL-6 receptor levels. The data together suggest that the IL-6 antibodies improve depressive symptoms in patients with RA and MCD. Further studies are needed to elucidate to what extents the IL-6 antibodies improve depressive symptoms through improving primary disease dependent and independent mechanisms, especially in RA patients, and the brain mechanisms underlying depressive symptom improvements. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical spectrum of Castleman disease–associated neuropathy

PubMed Central

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay

2016-01-01

Objective: To define the peripheral neuropathy phenotypes associated with Castleman disease. Methods: We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. Results: There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. Conclusion: There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. PMID:27807187

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review.

PubMed

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-06-01

TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

Current diagnosis and treatment of Castleman's disease.

PubMed

González García, A; Moreno Cobo, M Á; Patier de la Peña, J L

2016-04-01

Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Castleman's disease imitating adrenal mass in the retroperitoneal area.

PubMed

Koç, Gökhan; Turk, Hakan; Un, Sıtkı; Isoglu, Cemal Selcuk; Zorlu, Ferruh

2015-01-01

Castleman's disease (CD) is a non-clonal lymph node hyperplasia, mostly seen in the mediastinum. It has various clinical and pathological outcomes. There are different treatments because of its rare occurance and heterogenity. We present 2 cases which were referred to our clinic as retroperitoneal mass and diagnosed as CD after surgical resection.

Castleman's disease associated with a cerebellar chordoid meningioma and intestinal lymphangiectasia.

PubMed

Jeon, Chul Jin; Kim, Mi Jin; Lee, Jong Seung; Lee, Ji Hyuk; Kong, Doo-Sik; Shin, Hyung Jin; Suh, Yeon Lim; Kim, Kyoung Mee; Choe, Yon Ho

2010-11-01

Castleman's disease (CD) is a rare nonneoplastic lymphoproliferative disorder of unknown etiology. It is characterized by enlarged hyperplastic lymph nodes, usually presenting as a localized mass. Although an intracranial location is very uncommon, it should be considered in the differential diagnosis of a chordoid meningioma. We describe a pediatric case of CD with a cerebellar chordoid meningioma and intestinal lymphangiectasia.

Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review

PubMed Central

Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

2018-01-01

Abstract Rationale: TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Patient concerns: Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. Diagnoses: In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients’ laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. Interventions and outcomes: In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. Lessons: This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome. PMID:29879072

Identification of Novel Kaposi's Sarcoma-Associated Herpesvirus Orf50 Transcripts: Discovery of New RTA Isoforms with Variable Transactivation Potential

PubMed Central

Wakeman, Brian S.; Izumiya, Yoshihiro

2016-01-01

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma and multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50. RTA is a known transactivator of multiple viral genes, allowing it to control the switch between latency and virus replication. We report here the identification of six alternatively spliced Orf50 transcripts that are generated from four distinct promoters. These newly identified promoters are shown to be transcriptionally active in 293T (embryonic kidney), Vero (African-green monkey kidney epithelial), 3T12 (mouse fibroblast), and RAW 264.7 (mouse macrophage) cell lines. Notably, the newly identified Orf50 transcripts are predicted to encode four different isoforms of the RTA which differ by 6 to 10 residues at the amino terminus of the protein. We show the global viral transactivation potential of all four RTA isoforms and demonstrate that all isoforms can transcriptionally activate an array of KSHV promoters to various levels. The pattern of transcriptional activation appears to support a transcriptional interference model within the Orf50 region, where silencing of previously expressed isoforms by transcription initiation from upstream Orf50 promoters has the potential to modulate the pattern of viral gene activation. IMPORTANCE Gammaherpesviruses are associated with the development of lymphomas and lymphoproliferative diseases, as well as several other types of cancer. The human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is tightly associated with the development of Kaposi's sarcoma and multicentric Castleman's disease, as well as a rare form of B cell lymphoma (primary effusion lymphoma) primarily observed in HIV-infected individuals. RTA is an essential viral gene product involved in the initiation of gammaherpesvirus replication and is conserved among all known gammaherpesviruses. We show here for KSHV that transcription of the gene encoding RTA is complex and leads to the expression of several isoforms of RTA with distinct functions. This observed complexity in KSHV RTA expression and function likely plays a critical role in the regulation of downstream viral and cellular gene expression, leading to the efficient production of mature virions. PMID:27795414

Castleman's disease presenting as a pleural tumor: a case report with CT findings.

PubMed

Doo, Kyung Won; Kim, Bomi

2018-02-01

Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder which most commonly involves the mediastinum but rarely affects the pleura. We report a case of unicentric CD that presents as a pleural mass in a 45-year-old man, which was subsequently resected followed by an unexpected diagnosis on histologic examination. Although rare, CD should be included in the differential diagnosis of well-enhancing pleural mass.

Establishment of an ELISA to detect Kaposi's sarcoma-associated herpesvirus using recombinant ORF73.

PubMed

Ouyang, Xin-xing; Fu, Bi-shi; Li, Bao-lin; Zeng, Yan; Xu, Fan-hong; Wang, Lin-ding

2010-06-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and a proportion of cases of multicentric Castleman's disease (MCD). The ORF73 protein was cloned into pQE80L-orf73 and expressed in E.coli and purified. The expressed recombinant ORF73 was identified by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). A protein of about 27 kDa was expressed as expected. Western Blotting showed that the purified recombinant ORF73 reacted with KSHV positive serum. The immunogenicity of the recombinant ORF73 was further analysed by ELISA and the optimal conditions were determined. The ORF73 ELISA was used to compare the KSHV seroprevalence between Hubei and Xinjiang Han people. The Han people in Xinjiang have significantly higher KSHV seroprevalence than their counterparts in Hubei (6.7% vs 2.9%, P = 0.005).

Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma– associated herpesvirus

PubMed Central

Nun, Tamara K.; Kroll, David J.; Oberlies, Nicholas H.; Soejarto, Djaja D.; Case, Ryan J.; Piskaut, Pius; Matainaho, Teatulohi; Hilscher, Chelsey; Wang, Ling; Dittmer, Dirk P.; Gao, Shou-Jiang; Damania, Blossom

2013-01-01

Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma–associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death. PMID:17699731

The number and growth pattern of plasmacytoid dendritic cells vary in different types of reactive lymph nodes: an immunohistochemical study.

PubMed

Rollins-Raval, Marian A; Marafioti, Teresa; Swerdlow, Steven H; Roth, Christine G

2013-06-01

Plasmacytoid dendritic cells, which play a fundamental role in the innate immune response, are best known for their presence in hyaline-vascular Castleman disease and histiocytic necrotizing lymphadenitis. The relative number and distribution in many reactive entities as detected using more sensitive methods are uncertain, and their diagnostic implications are unknown. Immunohistochemical studies for plasmacytoid dendritic cell-associated markers CD123 and CD2AP were performed on 42 lymph nodes with hyaline-vascular Castleman disease, histiocytic necrotizing lymphadenitis, sarcoidosis, necrotizing granulomatous inflammation, viral infection, dermatopathic lymphadenopathy, autoimmune disease, and a histologic pattern compatible with toxoplasmosis. The overall plasmacytoid dendritic cell numbers and growth patterns (tight aggregates, loose aggregates/clusters, scattered single cells) were assessed. Plasmacytoid dendritic cells were present in all cases and were predominantly distributed in loose aggregates/clusters or singly. They were most numerous in granulomatous inflammation and histiocytic necrotizing lymphadenitis, whereas viral infections showed the fewest overall numbers and a predominant pattern of scattered single cells. Tight aggregates of plasmacytoid dendritic cells were most numerous in hyaline-vascular Castleman disease (100% sensitive, 68% specific). Plasmacytoid dendritic cells are not limited to a small number of reactive lymphadenopathies but are found in many reactive processes, often with a predominant pattern of loose aggregates/clusters and scattered single cells. However, tight aggregates were a characteristic feature of hyaline-vascular Castleman disease, and viral infections typically showed only few scattered cells distributed singly. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

PubMed Central

Polizzotto, Mark N.; Uldrick, Thomas S.; Hu, Duosha; Yarchoan, Robert

2012-01-01

Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or primary effusion lymphoma. Additional research is needed to better define the clinical spectrum of KICS and its relationship to KSHV–MCD. In additional, research is needed to better understand the pathogenesis and epidemiology of both KICS and KSHV–MCD, as well as the optimal therapy for both of these disorders. PMID:22403576

Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome.

PubMed

Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha; Yarchoan, Robert

2012-01-01

Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or primary effusion lymphoma. Additional research is needed to better define the clinical spectrum of KICS and its relationship to KSHV-MCD. In additional, research is needed to better understand the pathogenesis and epidemiology of both KICS and KSHV-MCD, as well as the optimal therapy for both of these disorders.

Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

PubMed Central

Yu, Li; Tu, Meifeng; Cortes, Jorge; Xu-Monette, Zijun Y.; Miranda, Roberto N.; Zhang, Jun; Orlowski, Robert Z.; Neelapu, Sattva; Boddu, Prajwal C.; Akosile, Mary A.; Uldrick, Thomas S.; Yarchoan, Robert; Medeiros, L. Jeffrey; Li, Yong; Fajgenbaum, David C.

2017-01-01

Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV-8–associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic [iMCD]). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic response of 96 patients (43 with UCD and 53 with iMCD) with HIV-/HHV-8–negative CD compared with 51 HIV-/HHV-8–positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD3+ lymphocytes (median, 58.88 ± 20.57) and lower frequency of CD19+/CD5+ (median, 5.88 ± 6.52) were observed in iMCD patients compared with UCD patients (median CD3+ cells, 43.19 ± 17.37; median CD19+/CD5+ cells, 17.37 ± 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response. PMID:28100459

Identification of Novel Kaposi's Sarcoma-Associated Herpesvirus Orf50 Transcripts: Discovery of New RTA Isoforms with Variable Transactivation Potential.

PubMed

Wakeman, Brian S; Izumiya, Yoshihiro; Speck, Samuel H

2017-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma and multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50 RTA is a known transactivator of multiple viral genes, allowing it to control the switch between latency and virus replication. We report here the identification of six alternatively spliced Orf50 transcripts that are generated from four distinct promoters. These newly identified promoters are shown to be transcriptionally active in 293T (embryonic kidney), Vero (African-green monkey kidney epithelial), 3T12 (mouse fibroblast), and RAW 264.7 (mouse macrophage) cell lines. Notably, the newly identified Orf50 transcripts are predicted to encode four different isoforms of the RTA which differ by 6 to 10 residues at the amino terminus of the protein. We show the global viral transactivation potential of all four RTA isoforms and demonstrate that all isoforms can transcriptionally activate an array of KSHV promoters to various levels. The pattern of transcriptional activation appears to support a transcriptional interference model within the Orf50 region, where silencing of previously expressed isoforms by transcription initiation from upstream Orf50 promoters has the potential to modulate the pattern of viral gene activation. Gammaherpesviruses are associated with the development of lymphomas and lymphoproliferative diseases, as well as several other types of cancer. The human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is tightly associated with the development of Kaposi's sarcoma and multicentric Castleman's disease, as well as a rare form of B cell lymphoma (primary effusion lymphoma) primarily observed in HIV-infected individuals. RTA is an essential viral gene product involved in the initiation of gammaherpesvirus replication and is conserved among all known gammaherpesviruses. We show here for KSHV that transcription of the gene encoding RTA is complex and leads to the expression of several isoforms of RTA with distinct functions. This observed complexity in KSHV RTA expression and function likely plays a critical role in the regulation of downstream viral and cellular gene expression, leading to the efficient production of mature virions. Copyright © 2016 American Society for Microbiology.

Castleman disease presenting as obstructive jaundice.

PubMed

Al-Salamah, Saleh M; Khan, Iftikhar A; Khalid, Kamran; Al-Shakweer, Wafaa A

2005-01-01

A 48-year-old Saudi male was admitted with features of obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed stricture in distal common bile duct CBD. Computed tomography scan revealed lymphadenopathy along CBD and in porta hepatis. Cholangiocarcinoma, lymphoma or metastatic deposits were suspected but no definite preoperative diagnosis could be established. Laparotomy disclosed lymph node enlargement in porta hepatis and along the CBD and lesser curvature of the stomach. Triple bypass procedure was performed to relieve the obstruction. Pathological examination of the lymph nodes showed Castleman disease of hyaline vascular type.

Unicentric Castleman's Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC.

PubMed

Luo, Yaping; Wang, Ling; Pan, Qingqing; Ma, Yanru; Li, Fang

2018-07-01

A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with Tc-HYNIC-TOC, but it was negative in I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman's disease, the hyaline vascular variant.

Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein

PubMed Central

Chatterjee, Deboeeta; Chandran, Bala

2012-01-01

Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is etiologically associated with three neoplastic syndromes: Kaposi sarcoma and the uncommon HIV-associated B-cell lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. The incidence of the latter B-cell pathology has been increasing in spite of antiretroviral therapy; its association with lytic virus replication has prompted interest in therapeutic strategies aimed at this phase of the virus life cycle. We designed and expressed a recombinant immunotoxin (2014-PE38) targeting the gpK8.1A viral glycoprotein expressed on the surface of the virion and infected cells. We show that this immunotoxin selectively kills KSHV-infected cells in dose-dependent fashion, resulting in major reductions of infectious virus release. The immunotoxin and ganciclovir, an inhibitor of viral DNA replication, showed marked reciprocal potentiation of antiviral activities. These results suggest that the immunotoxin, alone or in combination, may represent a new approach to treat diseases associated with KSHV lytic replication. PMID:22377676

The Clinical and Immunologic Features of Patients With Combined Anti-GBM Disease and Castleman Disease.

PubMed

Gu, Qiu-Hua; Jia, Xiao-Yu; Hu, Shui-Yi; Wang, Su-Xia; Zou, Wan-Zhong; Cui, Zhao; Zhao, Ming-Hui

2018-06-01

Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration.

PubMed

Giffin, Louise; West, John A; Damania, Blossom

2015-12-08

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi's sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6's impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and de novo KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with the development of three human malignancies, Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. KSHV expresses many factors that enable the virus to manipulate the host environment in order to persist and induce disease. The viral interleukin-6 (vIL-6) produced by KSHV is structurally and functionally homologous to the human cytokine interleukin-6, except that vIL-6 is secreted slowly and functions primarily from inside the host cell. To investigate the unique intracellular role of vIL-6, we analyzed the impact of vIL-6 on endothelial cell gene expression. We report that vIL-6 significantly alters the expression of genes associated with cell movement, including that for CEACAM1. The gene for CEACAM1 was upregulated by vIL-6 and by latent and primary KSHV infection and promotes vIL-6-mediated endothelial cell migration. This work advances the field's understanding of vIL-6 function and its contribution to KSHV pathogenesis. Copyright © 2015 Giffin et al.

Lymphoid disorders associated with HHV-8/KSHV infection: facts and contentions.

PubMed

Gaidano, G; Castaños-Velez, E; Biberfeld, P

1999-04-01

Following the demonstration in 1994, that Kaposi's sarcoma (KS) was associated with a novel virus (KSHV or HHV-8) belonging to the lymphotropic herpes family, this virus was also found in certain lymphoid neoplasias of immunodeficient (HIV+) and immune competent hosts. The association of HHV-8/KSHV infection is now well established with primary effusion lymphoma (PEL) or body cavity based lymphoma (BCBL) and multicentric Castleman's disease (MCD) of the plasma cell type. A possible pathogenic role of HHV-8/KSHV in other lymphoid tumours including primary central nervous system lymphoma (PCNSL) and multiple myeloma (MM) as well as some atypical lymphoproliferations and sarcoidosis has also been suggested, but this is at present a controversial matter, or not confirmed. Several HHV-8/KSHV genes, including potential oncogenes, genes homologous to various cellular genes and growth factors have been incriminated in the pathogenesis of KS and PEL/BCBL, but a common pathogenic mechanism for the clearly diverse proliferations represented by PEL, MCD and KS is at present not evident.

KSHV LANA inhibits TGF-β signaling through epigenetic silencing of the TGF-β type II receptor

PubMed Central

Di Bartolo, Daniel L.; Cannon, Mark; Liu, Yi-Fang; Renne, Rolf; Chadburn, Amy; Boshoff, Chris

2008-01-01

Signaling through the transforming growth factor–β (TGF-β) pathway results in growth inhibition and induction of apoptosis in various cell types. We show that this pathway is blocked in Kaposi sarcoma herpesvirus (KSHV)–infected primary effusion lymphoma through down-regulation of the TGF-β type II receptor (TβRII) by epigenetic mechanisms. Our data also suggest that KSHV infection may result in lower expression of TβRII in Kaposi sarcoma and multicentric Castleman disease. KSHV-encoded LANA associates with the promoter of TβRII and leads to its methylation and to the deacetylation of proximal histones. Reestablishment of signaling through this pathway reduces viability of these cells, inferring that KSHV-mediated blockage of TGF-β signaling plays a role in the establishment and progression of KSHV-associated neoplasia. These data suggest a mechanism whereby KSHV evades both the antiproliferative effects of TGF-β signaling by silencing TβRII gene expression and immune recognition by suppressing TGF-β–responsive immune cells through the elevated secretion of TGF-β1. PMID:18199825

Kaposi sarcoma herpesvirus pathogenesis

PubMed Central

Koch, Sandra; Schulz, Thomas F.

2017-01-01

Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

DOE Office of Scientific and Technical Information (OSTI.GOV)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activatedmore » GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.« less

[Analysis of the diagnosis and treatment of Castleman disease originating in the head and neck].

PubMed

Liu, L; Wang, L F; Sang, J Z; Chen, L

2018-06-05

Objective: To improve diagnosis and treatment of Castleman' s disease (CD) originating in the head and neck. Method: Of 15 cases of Castleman' s disease originating in the head and neck, 8 cases occurred in the right side of the neck, 6 cases in the left side, and 1 case in both sides. Eleven cases were focal type CD (UCD), and 4 cases were multi-center type CD (MCD). All patients underwent imaging examination and neck nephrectomy. Four patients with MCD received drug treatment after surgery. Result: During follow-up from 12 to 69 months, one patient suffered a slight facial paralysis due to a close relationship between mass and the parotid gland. One patient had obvious postoperative scar growth and occasional itching; another patient suffered mild pain in shoulder;4 cases of multi-center patients survived with tumor; 2 cases lost follow-up at 57 months, 65 months after follow-up, respectively. There were no recurrence in these two cases during the follow-up period; the remaining 6 cases had no exceptions. Conclusion: The clinical manifestations of CD patients are different. Pathological examination is an important basis for diagnosis. After a definite diagnosis, related examinations need to be completed. The LCD patients generally had a good prognosis, and the MCD patients often had a poor prognosis. For patients with parapharyngeal masses complicated by thyroid tumors, surgery can be performed at the same time.. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

IL-6 blockade in the management of non-infectious uveitis.

PubMed

Lopalco, Giuseppe; Fabiani, Claudia; Sota, Jurgen; Lucherini, Orso Maria; Tosi, Gian Marco; Frediani, Bruno; Iannone, Florenzo; Galeazzi, Mauro; Franceschini, Rossella; Rigante, Donato; Cantarini, Luca

2017-07-01

Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases. Interleukin (IL)-6 holds a critical role in the pathogenic pathways of uveitis, due to its extended and protean range of effects. On this background, manipulation of IL-6 inflammatory cascade has unraveled encouraging outcomes. For instance, rising evidence has been achieved regarding the successful use of tocilizumab, the humanized monoclonal antibody targeted against the IL-6 receptor, in treating uveitis related to juvenile idiopathic arthritis or Behçet's disease. Similar findings have also been reported for uveitis associated with systemic disorders, such as rheumatoid arthritis or multicentric Castleman disease, but also for idiopathic uveitis, the rare birdshot chorioretinopathy, and even in cases complicated by macular edema. This work provides a digest of all current experiences and evidences concerning IL-6 blockade, as suggested by the medical literature, proving its potential role in the management of non-infectious uveitis.

Thoracic Diseases Associated with HIV Infection in the Era of Antiretroviral Therapy: Clinical and Imaging Findings

PubMed Central

Prabhu, Somnath J.; Crothers, Kristina; Stern, Eric J.; Godwin, J. David; Pipavath, Sudhakar N.

2014-01-01

The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness. Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count. Primary lung cancer and Hodgkin lymphoma are two important non–AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma–associated herpesvirus (KSHV), is strongly linked to HIV-related diseases, including Kaposi sarcoma, multicentric Castleman disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. Immune reconstitution inflammatory syndrome is a direct complication of ART whose manifestations vary with the underlying disease. Given the high rate of smoking among HIV-infected patients, chronic obstructive pulmonary disease is another important cause of morbidity and mortality. A high degree of suspicion is required for the early diagnosis of pulmonary arterial hypertension and lymphocytic interstitial pneumonia, given their nonspecific manifestations. Finally, multilocular thymic cyst manifests as a cystic anterior mediastinal mass. Recognition of the clinical and radiologic manifestations of these less traditional HIV-related diseases can expedite diagnosis and treatment in the ART era. © RSNA, 2014 PMID:25019430

Clinical spectrum of intrathoracic Castleman disease: a retrospective analysis of 48 cases in a single Chinese hospital.

PubMed

Luo, Jin Mei; Li, Shan; Huang, Hui; Cao, Jian; Xu, Kai; Bi, Ya Lan; Feng, Rui E; Huang, Cheng; Qin, Ying Zhi; Xu, Zuo Jun; Xiao, Yi

2015-04-09

Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died. Intrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD's.

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

PubMed Central

Ablashi, Dharam V.; Chatlynne, Louise G.; Whitman, Jr., James E.; Cesarman, Ethel

2002-01-01

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus). Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial. The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus. PMID:12097251

/sup 75/Se-selenomethionine scintigraphy in mediastinal diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masaoka, A.; Kyo, S.

1978-03-01

Chest scanning with /sup 75/Se-selenomethionine was performed in 59 cases of mediastinal diseases. All cases of vascular diseases, cystic tumors, and benign neurogenic tumor were negatively scanned. Parenchymatous teratoma, thymoma, malignant lymphoma, Castleman's tumor, epithelial tumors, tuberculous lymphadenitis, and sarcoidosis showed high positive rates. In myasthenic thymus without thymoma two out of 15 cases were positive. The scan images of the resected specimens and preoperative chest scannings coincided.

Maladie de Castleman: localisation inhabituelle du thorax

PubMed Central

Eloueriachi, Fayçal; Caidi, Mohammed; Zouaidia, Fouad; Ouchen, Fahd; Maidi, Mehdi; Fennane, Hicham; Bouchikh, Mohamed; Achir, Abdellah; Benosman, Abdellatif

2012-01-01

La maladie de Castleman est une affection rare qui peut toucher le thorax. La localisation diaphragmatique est exceptionnelle. Nous rapportons le cas d'une patiente de 47 ans, chez qui une thoracotomie exploratrice a permis l'exérèse d'une masse du sinus médiastinal antérieur droit, en continuité avec le diaphragme et dont l'histologie est en faveur de la maladie de Castleman de type hyalino-vasculaire. Les particularités cliniques, radiologiques et évolutives ont été revues. PMID:23133711

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

PubMed

Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Chest neoplasms with infectious etiologies.

PubMed

Restrepo, Carlos S; Chen, Melissa M; Martinez-Jimenez, Santiago; Carrillo, Jorge; Restrepo, Catalina

2011-12-28

A wide spectrum of thoracic tumors have known or suspected viral etiologies. Oncogenic viruses can be classified by the type of genomic material they contain. Neoplastic conditions found to have viral etiologies include post-transplant lymphoproliferative disease, lymphoid granulomatosis, Kaposi's sarcoma, Castleman's disease, recurrent respiratory papillomatosis, lung cancer, malignant mesothelioma, leukemia and lymphomas. Viruses involved in these conditions include Epstein-Barr virus, human herpes virus 8, human papillomavirus, Simian virus 40, human immunodeficiency virus, and Human T-lymphotropic virus. Imaging findings, epidemiology and mechanism of transmission for these diseases are reviewed in detail to gain a more thorough appreciation of disease pathophysiology for the chest radiologist.

Carboxyl-Terminal Amino Acids 1052 to 1082 of the Latency-Associated Nuclear Antigen (LANA) Interact with RBP-Jκ and Are Responsible for LANA-Mediated RTA Repression

PubMed Central

Jin, Yi; He, Zhiheng; Liang, Deguang; Zhang, Quanzhi; Zhang, Hongxing; Deng, Qiang

2012-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is closely associated with several malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV can establish lifelong latency in the host, but the mechanism is not fully understood. Previous studies have proposed a feedback model in which the viral replication and transcription activator (RTA) can induce the expression of the latency-associated nuclear antigen (LANA) during early infection. LANA, in turn, represses transcription and RTA function to establish and maintain KSHV latency. The interaction between LANA and the recombination signal sequence binding protein Jκ (RBP-Jκ, also called CSL), a major transcriptional repressor of the Notch signaling pathway, is essential for RTA repression. In the present study, we show that the LANA carboxyl-terminal amino acids 1052 to 1082 are responsible for the LANA interaction with RBP-Jκ. The secondary structure of the LANA carboxyl terminus resembles the RBP-Jκ-associated module (RAM) of Notch receptor. Furthermore, deletion of the region of LANA residues 1052 to 1082 resulted in aberrant expression of RTA, leading to elevated viral lytic replication. For the first time, we dissected a conserved RBP-Jκ binding domain in LANA and demonstrated that this domain was indispensable for LANA-mediated repression of KSHV lytic genes, thus helping the virus maintain latency and control viral reactivation. PMID:22379075

Carboxyl-terminal amino acids 1052 to 1082 of the latency-associated nuclear antigen (LANA) interact with RBP-Jκ and are responsible for LANA-mediated RTA repression.

PubMed

Jin, Yi; He, Zhiheng; Liang, Deguang; Zhang, Quanzhi; Zhang, Hongxing; Deng, Qiang; Robertson, Erle S; Lan, Ke

2012-05-01

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is closely associated with several malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV can establish lifelong latency in the host, but the mechanism is not fully understood. Previous studies have proposed a feedback model in which the viral replication and transcription activator (RTA) can induce the expression of the latency-associated nuclear antigen (LANA) during early infection. LANA, in turn, represses transcription and RTA function to establish and maintain KSHV latency. The interaction between LANA and the recombination signal sequence binding protein Jκ (RBP-Jκ, also called CSL), a major transcriptional repressor of the Notch signaling pathway, is essential for RTA repression. In the present study, we show that the LANA carboxyl-terminal amino acids 1052 to 1082 are responsible for the LANA interaction with RBP-Jκ. The secondary structure of the LANA carboxyl terminus resembles the RBP-Jκ-associated module (RAM) of Notch receptor. Furthermore, deletion of the region of LANA residues 1052 to 1082 resulted in aberrant expression of RTA, leading to elevated viral lytic replication. For the first time, we dissected a conserved RBP-Jκ binding domain in LANA and demonstrated that this domain was indispensable for LANA-mediated repression of KSHV lytic genes, thus helping the virus maintain latency and control viral reactivation.

Close but Distinct Regions of Human Herpesvirus 8 Latency-Associated Nuclear Antigen 1 Are Responsible for Nuclear Targeting and Binding to Human Mitotic Chromosomes

PubMed Central

Piolot, Tristan; Tramier, Marc; Coppey, Maité; Nicolas, Jean-Claude; Marechal, Vincent

2001-01-01

Human herpesvirus 8 is associated with all forms of Kaposi's sarcoma, AIDS-associated body cavity-based lymphomas, and some forms of multicentric Castleman's disease. Herpesvirus 8, like other gammaherpesviruses, can establish a latent infection in which viral genomes are stably maintained as multiple episomes. The latent nuclear antigen (LANA or LNAI) may play an essential role in the stable maintenance of latent episomes, notably by interacting concomitantly with the viral genomes and the metaphase chromosomes, thus ensuring an efficient transmission of the neoduplicated episomes to the daughter cells. To identify the regions responsible for its nuclear and subnuclear localization in interphase and mitotic cells, LNAI and various truncated forms were fused to a variant of green fluorescent protein. This enabled their localization and chromosome binding activity to be studied by low-light-level fluorescence microscopy in living HeLa cells. The results demonstrate that nuclear localization of LNAI is due to a unique signal, which maps between amino acids 24 and 30. Interestingly, this nuclear localization signal closely resembles those identified in EBNA1 from Epstein-Barr virus and herpesvirus papio. A region encompassing amino acids 5 to 22 was further proved to mediate the specific interaction of LNA1 with chromatin during interphase and the chromosomes during mitosis. The presence of putative phosphorylation sites in the chromosome binding sites of LNA1 and EBNA1 suggests that their activity may be regulated by specific cellular kinases. PMID:11264383

Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

PubMed

Cousins, Emily; Nicholas, John

2014-01-01

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

PubMed

Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa

2012-06-01

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

An Unusual Presentation of Plasma Cells - Castleman Disease: A Case Report.

PubMed

Mihăilă, Mariana; Herlea, V; Dobrea, Camelia; Lupescu, Ioana; Munteanu, Gina Rusu; Chiriac, Grethi; Micu, L; Serescu, R; Copaci, I

2016-01-01

We present the case of a 76 year old female patient admitted in the Department of Cardiology for physical asthenia, profuse sweating and dyspnea with orthopnea for about one month. Clinical and paraclinical assessments performed at admission confirmed the diagnosis of cardiac tamponade. Surgical intervention was performed and 400 mL of clear effusion were drained. Post-operative evolution was marked by recurrence of symptoms, requiring after 3 weeks a new drainage of 600 mL of clear effusion, and biopsy of the pericardium was performed. Pathological exam described serous pericarditis with chronic inflammatory infiltrate, xanthogranulomatous reaction intricated in the pericardium and mesothelial hyperplasia. The patient was subsequently transferred to the Department of Internal Medicine for further investigations. Physical examination showed a patient with altered general status, pallor, vesicular murmur absent in both bases, presenting cutaneous hyperpigmentation at the level of the right hemi-abdomen and hip with posterior extension, and a peripheral indurated erythematous plaque. The patient presented nodular masses of 3 cm in the right latero-cervical and bilateral axillary regions, non-adherent to the superficial structures, as well as adenopathic blocks in both inguinal regions. CT scan of the thorax and abdomen showed moderate bilateral pleuresia, minimal pericardial effusion (15 mm) and multiple adenopathies on both sides of the diaphragm. Skin biopsy was performed, as well as bone marrow aspirate and excision of a right axillary lymph node. Pathological exams and immunohistochemistry tests confirmed the diagnosis of Plasma Cells Castleman disease.

Human herpesvirus 8 infections in patients with immunodeficiencies.

PubMed

Laurent, Camille; Meggetto, Fabienne; Brousset, Pierre

2008-07-01

In 1994, Chang et al described a novel herpesvirus in tissues from patients with Kaposi sarcoma, referred to as Kaposi sarcoma herpesvirus or human herpesvirus 8. They used a very sophisticated technique of molecular biology to isolate unknown DNA sequences from Kaposi sarcoma lesions, which were not present in normal tissues. It turned out that these sequences corresponded to a previously unrecognized gamma herpesvirus highly homologous to human herpesvirus 4 (Epstein-Barr virus) and to herpesvirus saimiri. Contrary to Epstein-Barr virus, human herpesvirus 8 is not ubiquitous. The seroprevalence of human herpesvirus 8 varies greatly worldwide, with 1% to 10% of people being infected in developed countries and up to 80% of infected individuals in some areas of sub-Saharan and equatorial Africa. Human herpesvirus 8 is associated with a limited spectrum of tumors, mostly observed in immunodeficient individuals with HIV infection. Beside Kaposi sarcoma and multicentric Castleman disease, human herpesvirus 8 is associated with primary effusion lymphoma, but unlike Epstein-Barr virus, human herpesvirus 8 is not involved in epithelial tumors. Different proteins of the virus can be detected in infected cells. Antibodies against the latent nuclear antigen 1 are available in routine pathology and represent a powerful tool to detect the virus in human tissues. Although Epstein-Barr virus is the most frequent causative agent of lymphomas in immunocompromised individuals, a systematic screening of such tumors with specific antibodies reveals that the implication of human herpesvirus 8 infection is probably underestimated. Recent descriptions of non-Hodgkin lymphoma in endemic areas, solid localizations of primary effusion lymphoma, and posttransplantation lymphoproliferations have expanded the spectrum of human herpesvirus 8-related lymphoproliferative disorders. In this review, we will be presenting an overview of the recent concepts regarding human herpesvirus 8 and related disorders.

Human herpesvirus 8 infection among various population groups in southern Israel.

PubMed

Margalith, Miriam; Chatlynne, Louise G; Fuchs, Efrat; Owen, Carole; Lee, Cheng-Rei Ruth; Yermiyahu, Tikva; Whitman, James E; Ablashi, Dharam V

2003-12-15

To compare the prevalence of antibodies to human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus among Israeli and Ethiopian subjects. Serum samples were obtained from 98 Israeli Jewish students aged 18-30 years, 100 HIV-1-seronegative Ethiopian immigrants to Israel of the same age, and 100 HIV-1-seronegative Ethiopian children 1-12 years old upon their arrival in southern Israel. Plasma samples were obtained from 3 hospitalized patients with multicentric Castleman disease (MCD) as positive controls. All serum samples were tested for antibodies to both latent and lytic antigens. Antibodies to the lytic antigens and the latency-associated nuclear antigen (LANA) of HHV-8 were detected by enzyme linked immunosorbent assay and by immunofluorescence assay. HHV-8 DNA from serum or plasma samples was detected by polymerase chain reaction analysis. Antibodies to HHV-8 LANA were detected in 2.9% of the Israeli subjects aged 18-30 years and in 26% of the Ethiopian subjects from both age groups tested. Antibodies to the lytic antigens were detected in all 3 MCD patients, in 4% of the Ethiopian children, and in 2% of the 18- to 30-year-old Ethiopians. No antibodies to the lytic antigens were detected in the Israeli students. HHV-8 DNA was detected in all 3 MCD patients and in 2 of 4 of the Ethiopian children positive for the lytic antigens. HHV-8 is highly prevalent in Ethiopian immigrants to Israel as compared with Israeli students. Antibodies to HHV-8 in Ethiopia are acquired before puberty. The results of this study indicate the association of HHV-8 with MCD, as has been documented by many other researchers.

Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

PubMed

Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

2018-05-01

Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

Tribute to A. W. Castleman, Jr.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knappenberger, Jr., Kenneth L.; Johnson, Grant E.; El-Sayed, Mostafa A.

It is with great pleasure that we join our many colleagues who contributed to this special issue of The Journal of Physical Chemistry A in dedicating it in honor of Professor A. W. “Will” Castleman, Jr. Will is a pioneer in the field of cluster science, and the far-reaching impact of his career is demonstrated by the broad range of topics covered in this issue. This diversity validates Will’s teaching that “fundamental research in cluster science allows you to explore any problem you want”. This ability to extend to other research areas comes because, as Will has shown both rigorouslymore » and elegantly, clusters are an intermediate state of matter that bridge the gap between molecular and bulk levels.« less

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Identification of Caspase Cleavage Sites in KSHV Latency-Associated Nuclear Antigen and Their Effects on Caspase-Related Host Defense Responses.

PubMed

Davis, David A; Naiman, Nicole E; Wang, Victoria; Shrestha, Prabha; Haque, Muzammel; Hu, Duosha; Anagho, Holda A; Carey, Robert F; Davidoff, Katharine S; Yarchoan, Robert

2015-07-01

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of three hyperproliferative disorders: Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. During viral latency a small subset of viral genes are produced, including KSHV latency-associated nuclear antigen (LANA), which help the virus thwart cellular defense responses. We found that exposure of KSHV-infected cells to oxidative stress, or other inducers of apoptosis and caspase activation, led to processing of LANA and that this processing could be inhibited with the pan-caspase inhibitor Z-VAD-FMK. Using sequence, peptide, and mutational analysis, two caspase cleavage sites within LANA were identified: a site for caspase-3 type caspases at the N-terminus and a site for caspase-1 and-3 type caspases at the C-terminus. Using LANA expression plasmids, we demonstrated that mutation of these cleavage sites prevents caspase-1 and caspase-3 processing of LANA. This indicates that these are the principal sites that are susceptible to caspase cleavage. Using peptides spanning the identified LANA cleavage sites, we show that caspase activity can be inhibited in vitro and that a cell-permeable peptide spanning the C-terminal cleavage site could inhibit cleavage of poly (ADP-ribose) polymerase and increase viability in cells undergoing etoposide-induced apoptosis. The C-terminal peptide of LANA also inhibited interleukin-1 beta (IL-1β) production from lipopolysaccharide-treated THP-1 cells by more than 50%. Furthermore, mutation of the two cleavage sites in LANA led to a significant increase in IL-1β production in transfected THP-1 cells; this provides evidence that these sites function to blunt the inflammasome, which is known to be activated in latently infected PEL cells. These results suggest that specific caspase cleavage sites in KSHV LANA function to blunt apoptosis as well as interfere with the caspase-1-mediated inflammasome, thus thwarting key cellular defense mechanisms.

Single Molecule Analysis of Replicated DNA Reveals the Usage of Multiple KSHV Genome Regions for Latent Replication

PubMed Central

Verma, Subhash C.; Lu, Jie; Cai, Qiliang; Kosiyatrakul, Settapong; McDowell, Maria E.; Schildkraut, Carl L.; Robertson, Erle S.

2011-01-01

Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences. PMID:22072974

Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

PubMed Central

Thorpe, Steven W.; Weiss, Kurt R.; Goodman, Mark A.; Heyl, Alma E.; McGough, Richard L.

2012-01-01

In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease. PMID:22550427

[AA amyloidosis].

PubMed

Stojanovic, Katia Stankovic; Georgin-Lavialle, Sophie; Grateau, Gilles

2017-06-01

AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Aggressive TAFRO syndrome with reversible cardiomyopathy successfully treated with combination chemotherapy.

PubMed

Yasuda, Shunichiro; Tanaka, Keisuke; Ichikawa, Ayako; Watanabe, Ken; Uchida, Emi; Yamamoto, Masahide; Yamamoto, Kouhei; Mizuchi, Daisuke; Miura, Osamu; Fukuda, Tetsuya

2016-10-01

TAFRO (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) syndrome is an atypical manifestation of Castleman's disease. However, the mechanism underlying this very rare syndrome remains unknown, and there is no established standard treatment. Here we report cases of two young females with TAFRO syndrome who showed similar clinical courses. Both cases showed severe anasarca, ascites, and thrombocytopenia. Although high-dose steroids were ineffective, combination chemotherapy showed remarkable effects. However, both patients developed severe but reversible heart failure after CHOP therapy owing to diffuse cardiomyopathy, which was presumably associated with TAFRO syndrome. Therefore, although combination chemotherapy may be very effective in the treatment of TAFRO syndrome, careful observation for cardiomyopathy development is needed, particularly when using adriamycin-containing regimens.

The frequency of occurrence and nature of recombinant feline leukemia viruses in the induction of multicentric lymphoma by infection of the domestic cat with FeLV-945.

PubMed

Ahmad, Shamim; Levy, Laura S

2010-08-01

During feline leukemia virus (FeLV) infection in the domestic cat, viruses with a novel envelope gene arise by recombination between endogenous FeLV-related elements and the exogenous infecting species. These recombinant viruses (FeLV-B) are of uncertain disease association, but have been linked to the induction of thymic lymphoma. To assess the role of FeLV-B in the induction of multicentric lymphoma and other non-T-cell disease, the frequency of occurrence and nature of FeLV-B were examined in diseased tissues from a large collection of FeLV-infected animals. Diseased tissues were examined by Southern blot and PCR amplification to detect the presence of FeLV-B. Further analysis was performed to establish the recombination junctions and infectivity of FeLV-B in diseased tissues. The results confirmed the frequent association of FeLV-B with thymic lymphoma but showed infrequent generation, low levels and lack of infectivity of FeLV-B in non-T-cell diseases including multicentric lymphoma.

The paradigm of IL-6: from basic science to medicine.

PubMed

Naka, Tetsuji; Nishimoto, Norihiro; Kishimoto, Tadamitsu

2002-01-01

IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemia inhibitory factor and oncostatin M. The pleiotropy and redundancy of IL-6 functions have been identified by using a unique receptor system comprising two functional proteins: an IL-6 receptor (IL-6R) and gp130, the common signal transducer of cytokines related to IL-6. Signal transduction through gp130 is mediated by two pathways: the JAK-STAT (Janus family tyrosine kinase-signal transducer and activator of transcription) pathway and the Ras mitogen-activated protein kinase pathway. The negative regulators of IL-6 signaling have also been identified, although the physiological roles of the molecules are not yet fully understood. The pathological roles of IL-6 have also been clarified in various disease conditions, such as inflammatory, autoimmune, and malignant diseases. On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Learning to Love Learning

ERIC Educational Resources Information Center

Castleman, Ben; Littky, Dennis

2007-01-01

Too often, teachers in public schools do not have the time to get to know their students or tailor their instruction to students' interests. As a result, many students lose interest in school. The Met School, a public high school in Providence, Rhode Island, is designed to help students enjoy school while learning real-world skills. Castleman and…

Glomeruloid hemangioma and POEMS syndrome.

PubMed

Hernández Aragüés, I; Pulido Pérez, A; Ciudad Blanco, C; Parra Blanco, V; Suárez Fernández, R

2017-03-01

POEMS syndrome is a paraneoplastic manifestation associated with hematopoietic disorders such as multiple myeloma and Castleman disease. POEMS is an acronym for the main clinical features of the syndrome, namely, Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin abnormalities. Glomeruloid hemangiomas are considered to be a specific clinical marker of POEMS syndrome. However, while they are not pathognomonic, their presence should raise suspicion of this syndrome or alert clinicians to its possible future development, as these lesions can appear years before the onset of the syndrome. We report the cases of 2 women with plasma cell dyscrasias and sudden onset of lesions with a vascular appearance and histologic findings consistent with glomeruloid hemangioma. Recognition of this vascular tumor is important for the early diagnosis of POEMS syndrome. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Multicentric squamous cell carcinona in a paca (Agouti paca) resembling Bowen's disease.

PubMed

Luppi, Marcela M; Malta, Marcelo C C; Costa, Maria E L T; Motta, Rafael O C; Santos, Renato L

2008-06-01

An 8-yr-old female paca (Agouti paca) was admitted at the Veterinary Hospital of the Belo Horizonte Zoo (Brazil) with an ulcerated cutaneous nodule of approximately 1.5 cm in diameter in the left ear. One week later, other cutaneous nodules were detected in various body locations. The animal died during a surgical procedure to remove the tumors. All cutaneous nodules were histologically similar with features of squamous cell carcinoma. Considering the predominant in situ nature of the lesion as well as its multicentric localization, the disease reported here closely resembles Bowen's disease, which has been described in humans and which has been identified as a rare neoplastic disease of cats, with one single report in a dog. This is the first report of a neoplastic disease in Agouti

Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers.

PubMed

Bottari, Nathieli B; Munhoz, Thiago D; Torbitz, Vanessa D; Tonin, Alexandre A; Anai, Letícia A; Semolin, Lívia M S; Jark, Paulo C; Bollick, Yãnaí S; Moresco, Rafael N; França, Raqueli T; Lopes, Sonia T A; Stefani, Lenita M; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

2015-01-01

Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group.

Multicentric primary extramammary Paget disease: a Toker cell disorder?

PubMed

Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

2014-07-01

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

Summer Melt: Supporting Low-Income Students through the Transition to College

ERIC Educational Resources Information Center

Castleman, Benjamin L.; Page, Lindsay C.

2014-01-01

Under increasing pressure to raise graduation rates and ensure that students leave high school college- and career-ready, many school and district leaders may believe that, when students graduate with college acceptances in hand, their work is done. But as Benjamin L. Castleman and Lindsay C. Page show, summer can be a time of significant…

International Rare Histiocytic Disorders Registry (IRHDR)

ClinicalTrials.gov

2018-04-18

Rare Histiocytic Disorders (RHDs); Juvenile Xanthogranuloma (JXG); Reticulohistiocytoma (Epithelioid Histiocytoma); Xanthoma Disseminatum (XD); Multicentric Reticulohistiocytosis (MRH); Systemic Juvenile Xanthogranuloma; Erdheim-Chester Disease (ECD); Multi-system Rosai-Dorfman Disease (RDD)

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Complicated Genitourinary Tract Infections and Mimics.

PubMed

Yu, Michael; Robinson, Kathryn; Siegel, Cary; Menias, Christine

This article provides pictorial review of complicated upper and lower genitourinary infections and their mimics. Imaging features of upper urinary tract infections including uncomplicated acute pyelonephritis, xanthogranulomatous pyelonephritis (XGPN), emphysematous pyelonephritis, perirenal abscess, and pyonephrosis are first reviewed and then followed by pictorial review of their mimics including contrast-associated nephrotoxicity, renal infarcts, malakoplakia, renal cell cancer, leukemia or lymphoma and Castleman's disease. Next, imaging features of lower urinary tract infections including cystitis, emphysematous cystitis, enterovesical, colovesical and vesicovaginal fistulas, Fournier gangrene, prostatitis, epididymitis, and orchitis are reviewed and then followed by pictorial review of their mimics including gas in the bladder and perineum related to instrumentation, radiation cystitis, bladder cancer, testicular torsion, testicular trauma, and testicular cancer and lymphoma. Recognizing imaging characteristics of complicated genitourinary infections and their mimics would allow clinicians to provide appropriate timely management. Copyright © 2016 Elsevier Inc. All rights reserved.

Summer Nudging: Can Personalized Text Messages and Peer Mentor Outreach Increase College Going among Low-Income High School Graduates?

ERIC Educational Resources Information Center

Castleman, Benjamin L.; Page, Lindsay C.

2016-01-01

A report released in April 2013 by Benjamin L Castleman of Harvard University and Lindsay C. Page of the Center for Education Policy Research at Harvard University examines the implications of two forms of interventions during the summer between high school and the first year of college on college enrollment. "Summer Nudging: Can Personalized…

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

PubMed

Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

2017-01-01

Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

[What's new in internal medicine?].

PubMed

Blétry, O; Sene, T; Kahn, J-E; Ackermann, F; Charles, P; Leport, J; Piette, A-M

2009-12-01

Among diagnostic progress over the last three years in internal medicine, Antisynthetase Syndrome is now more easily recognised with the diffusion of laboratory tests for research of antibodies against tRNA synthetases (Anti JO1, anti PL7, Anti PL12). In two third of cases, these antibodies are found despite absence of antinuclear antibodies. Hence, we have to search them specifically in patients with polyarthritis associated with myositis, cutaneous manifestations (Raynaud phenomenom and "mechanic'hands") and interstitial lung disease. Discovery of asymptomatic mutation in the L ferritin coding sequence help us to better understand the "unexplained" hyperferritinemia. Initially described by japonese gastroenterologists, auto immune pancreatitis in fact a part of a systemic sclerosing disease with a biochemical hallmark: in crease of a subclass of immunoglobulins G (IgG4). A new pediatric disease due to a deficiency of the interleukin1 receptor antagonist (multifocal aseptic osteitis, periostitis, stomatitis, disseminated pustulosis) help us to better understand unexplained auto inflammatory diseases. The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia. Copyright 2009 Elsevier Masson SAS. All rights reserved.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration.

PubMed

Chalmers, James D; Crichton, Megan; Goeminne, Pieter C; Loebinger, Michael R; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-09-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

PubMed Central

Crichton, Megan; Goeminne, Pieter C.; Loebinger, Michael R.; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja ; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-01-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. Educational aims To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areas To understand some of the key features of successful disease registries To review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 years To understand the key research priorities identified by EMBARC for the next 5 years PMID:28894479

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

PubMed

Marchewka, Artur; Kherif, Ferath; Krueger, Gunnar; Grabowska, Anna; Frackowiak, Richard; Draganski, Bogdan

2014-05-01

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS. Copyright © 2013 Wiley Periodicals, Inc.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Mulberry cells in the thyroid: warthin-finkeldey-like cells in hashimoto thyroiditis-associated lymphoma.

PubMed

Lapadat, Razvan; Nam, Moon Woo; Mehrotra, Swati; Velankar, Milind; Pambuccian, Stefan E

2017-03-01

Warthin-Finkeldey type giant cells were first described in autopsies performed on young children who died during the highly lethal measles epidemic in Palermo during the winter of 1908. The cells had 8-15 nuclei without identifiable cytoplasm within the germinal centers of lymphoid organs resembling megakaryocytes. We describe a case of Hashimoto thyroiditis with an enlarging substernal throid mass. The resection specimen contained many Warthin-Finkeldey-Like Cells (WFLC) in an extranodal marginal zone lymphoma (MALT type) with focal transformation to diffuse large B-cell lymphoma. The WFLC showed nuclear features similar to those of neighboring follicular dendritic cells (FDCs), favoring the hypothesis that these cells might be the product of fusion of FDCs. This is supported by immunostaining results and the occurrence of similar cells in follicular dendritic cell sarcomas and in "dysplastic" FDCs in hyaline vascular type Castleman disease, a possible precursor of follicular dendritic cell tumors. Diagn. Cytopathol. 2017;45:212-216. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Marine origin of pyritic sulfur in the Lower Bakerstown coal bed, Castleman coal field, Maryland (U.S.A.)

USGS Publications Warehouse

Lyons, P.C.; Whelan, J.F.; Dulong, F.T.

1989-01-01

The amount, kind, distribution, and genesis of pyrite in the Lower Bakerstown coal bed in a 150 ?? 15 m area of the Bettinger mine, Castleman coal field, Maryland, were studied by various analytical techniques. The mined coal, which had a nonmarine roof rock, contained 1.4-2.8 wt.% total sulfur, generally much lower than the high-sulfur coal (> 3.0 wt.% total S) to the north, which is associated with marine roof rocks. Small-scale systematic and nonsystematic variations in total sulfur and pyrite distribution were found in the mined area. In the column sample, most of the pyrite was found in the upper 9 cm of the 69-cm-thick mined coal and occurred mainly as a pyrite lens containing cell fillings in seed-fern tissue (coal ball). As-bearing pyrite was detected by laser microprobe techniques in the cell walls of this tissue but not elsewhere in the column sample. This may indicate that the As was derived from decomposition of organic matter in the cell walls. The sulfur isotopic composition and distribution of pyrite in the coal are consistent with introduction of marine sulfate shortly after peat deposition, followed by bacterial reduction and pyrite precipitation. Epigenetic cleat pyrite in the coal is isotopically heavy, implying that later aqueous sulfate was 34S-enriched. ?? 1989.

CADASIL: Treatment and Management Options.

PubMed

Bersano, Anna; Bedini, Gloria; Oskam, Joshua; Mariotti, Caterina; Taroni, Franco; Baratta, Silvia; Parati, Eugenio Agostino

2017-09-01

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods.

PubMed

Speicher, David J; Johnson, Newell W

2012-09-11

Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months. HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available in many parts of the world, including those with high prevalence of KS and HHV-8. A new molecular facility with stringent three-phase workflow was established, adhering to NPAAC and CLSI guidelines. Three fully validated quantitative assays were developed: two for detection and quantification of HHV-8; one for GAPDH, necessary for normalisation of viral loads in tissue and peripheral blood. The HHV-8 ORF73 and ORF26 qPCR assays were 100% specific. All qPCR assays, displayed a broad dynamic range (102 to 1010 copies/μL TE Buffer) with a limit of detection of 4.85x103, 5.61x102, and 2.59x102 copies/μL TE Buffer and a limit of quantification of 4.85x103, 3.01x102, and 1.38x102 copies/μL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and GAPDH respectively.The assays were tested on a panel of 35 KS biopsies from Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV-8 copies/μL DNA extract (range: 4.37x103 to 1.47x106 copies/μL DNA extract): When normalised these equate to an average viral load of 2.44x104 HHV-8 copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells). These are the first fully optimised, validated and MIQE compliant HHV-8 qPCR assays established in Australia. They worked well for qualitative detection of HHV-8 in archival tissue, and are well-suited for quantitative detection in whole blood. They are now available for research, for clinical diagnosis of HHV-8 infection, and for monitoring treatment efficacy.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

PubMed

Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

1999-11-01

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.

Successful treatment of deep vein thrombosis caused by iliac vein compression syndrome with a single-dose direct oral anti-coagulant.

PubMed

Nakashima, Naoya; Sueta, Daisuke; Kanemaru, Yusuke; Takashio, Seiji; Yamamoto, Eiichiro; Hanatani, Shinsuke; Kanazawa, Hisanori; Izumiya, Yasuhiro; Kojima, Sunao; Kaikita, Koichi; Hokimoto, Seiji; Tsujita, Kenichi

2017-01-01

Although vein stenting is popular for treatment for venous thromboembolism due to mechanical compression, some cases are forced to avoid inserting align agents because of immunodeficiency. An 82-year-old man with left extremity redness and swelling presented to a hospital for a medical evaluation. The patient was immunodeficient because of the adverse effects of his treatment for Castleman's disease. A contrast-enhanced computed tomography scan revealed a venous thromboembolism in inferior vena cava and the left lower extremity. Magnetic resonance venography showed that the iliac artery was compressing the iliac vein. We were reluctant to place a stent in the iliac vein has because of the patient's immunodeficient status. Three months of treatment using single-dose edoxaban (30 mg daily) resulted in complete resolution of the thrombus. This is the first report demonstrating that single-dose edoxaban without acute-phase parenteral anticoagulation is effective in the treatment of iliac vein compression. A single-dose direct oral anti-coagulant without acute-phase parenteral anticoagulation is effective for mechanical compression.

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

PubMed

Curran, K; Thamm, D H

2016-08-01

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. © 2015 John Wiley & Sons Ltd.

Work productivity and activity impairment in gastroesophageal reflux disease in Korean full-time employees: a multicentre study.

PubMed

Shin, Woon Geon; Kim, Heung Up; Kim, Sang Gyun; Kim, Gwang Ha; Shim, Ki-Nam; Kim, Jeong Wook; Kim, Jin Il; Kim, Jae Gyu; Kim, Jae J; Yim, Da-Hae; Park, Sue K; Park, Soo-Heon

2012-04-01

The costs of gastroesophageal reflux disease have not been assessed in Asia, even though the prevalence of gastroesophageal reflux disease is gradually increasing. We evaluated work presenteeism and absenteeism as indirect costs of gastroesophageal reflux disease in Korea. This was a cross-sectional and multicentre study using patient-reported outcome instruments. A total of 1009 full-time employees who visited the gastrointestinal department for any reason (281 patients with gastroesophageal reflux disease and 728 controls) were included. Main outcomes were presenteeism and absenteeism measured as work productivity loss and monetary cost per week. Absenteeism and presenteeism were significantly higher in the gastroesophageal reflux disease than the control group (1.49% vs. 0.46%, P=0.0010; 34.13% vs. 9.23%, P<0.0001). Loss of work productivity was significantly greater in the gastroesophageal reflux disease than the control group (33.09% vs. 9.02%; P<0.0001). This loss of work productivity difference between the two groups represented an additional productivity loss of 11.7h/week in the gastroesophageal reflux disease group compared with the control group. Assuming average hourly wages of $14.12, the weekly burden of gastroesophageal reflux disease reached $165.07 per person. Gastroesophageal reflux disease was associated with substantial work productivity loss, mainly due to presenteeism rather than absenteeism, in Korean full-time employees. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

WebBioBank: a new platform for integrating clinical forms and shared neurosignal analyses to support multi-centre studies in Parkinson's Disease.

PubMed

Rossi, Elena; Rosa, Manuela; Rossi, Lorenzo; Priori, Alberto; Marceglia, Sara

2014-12-01

The web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson's Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated. The aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson's Disease that integrates biosignal analysis tools and data collection in a shared and secure environment. We designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients' personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms. Four clinical research centres used WebBioBank for 1year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user's satisfaction mean score exceeded the satisfaction threshold. WebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients. Copyright © 2014 Elsevier Inc. All rights reserved.

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases.

PubMed

Rubbert-Roth, Andrea; Furst, Daniel E; Nebesky, Jan Michael; Jin, Angela; Berber, Erhan

2018-06-01

Tocilizumab (TCZ) is the first humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the long-term efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit, was recently approved for the treatment of patients with RA, although long-term data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents.

A Randomised Multi-centre Study to Compare the Long-term Performance of the Future Hip to 3 Other Implants in Primary Total Hip Replacement

ClinicalTrials.gov

2016-10-06

Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis; Perthes Disease

The role of radiotherapy in the management of POEMS syndrome.

PubMed

Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

2014-11-28

POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman's disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

Ten-year experience of transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension.

PubMed

Regnault, David; d'Alteroche, Louis; Nicolas, Charlotte; Dujardin, Fanny; Ayoub, Jean; Perarnau, Jean Marc

2018-05-01

Transjugular intrahepatic portosystemic shunt (TIPS) is considered to be well suited for the treatment of noncirrhotic portal hypertension (NCPHT) because of a usually severe portal hypertension (PHT) and a mild liver failure, but very less data are available. Records of patients referred for TIPS between 2004 and 2015 for NCPHT were reviewed. No patient should have clinical or biological or histological features of cirrhosis. Twenty-five patients with a wide variety of histological lesions (sinusoidal dilatations, granulomatosis, regenerative nodular hyperplasia, obliterative portal venopathy, or subnormal liver) and a wide variety of associated diseases (thrombophilia, sarcoidosis, common variable immunodeficiency, scleroderma, Castleman's disease, early primitive biliary cirrhosis, congenital liver fibrosis, chemotherapy, purinethol intake, and congenital varices) were included. Two complications occurred during the procedure: one periprosthetic hematoma and the other misposition of a covered stent. During the first month, two other patients had an early thrombosis, another had induced encephalopathy, and one died of early rebleeding. Two of these complications occurred in patients with cavernoma. With a mean follow-up of 39 months, 10 patients experienced at least one episode of spontaneous encephalopathy, with three of these patients requiring a stent reduction. Five patients had a recurrence of their initial symptoms, and one had an asymptomatic hemodynamic dysfunction. TIPS is effective in NCPHT but can be technically difficult, especially in the case of cavernoma. Good liver function does not prevent the occurrence of long-term encephalopathy.

Interleukin-6: structure-function relationships.

PubMed Central

Simpson, R. J.; Hammacher, A.; Smith, D. K.; Matthews, J. M.; Ward, L. D.

1997-01-01

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines. PMID:9144766

Evaluation of web-based annotation of ophthalmic images for multicentric clinical trials.

PubMed

Chalam, K V; Jain, P; Shah, V A; Shah, Gaurav Y

2006-06-01

An Internet browser-based annotation system can be used to identify and describe features in digitalized retinal images, in multicentric clinical trials, in real time. In this web-based annotation system, the user employs a mouse to draw and create annotations on a transparent layer, that encapsulates the observations and interpretations of a specific image. Multiple annotation layers may be overlaid on a single image. These layers may correspond to annotations by different users on the same image or annotations of a temporal sequence of images of a disease process, over a period of time. In addition, geometrical properties of annotated figures may be computed and measured. The annotations are stored in a central repository database on a server, which can be retrieved by multiple users in real time. This system facilitates objective evaluation of digital images and comparison of double-blind readings of digital photographs, with an identifiable audit trail. Annotation of ophthalmic images allowed clinically feasible and useful interpretation to track properties of an area of fundus pathology. This provided an objective method to monitor properties of pathologies over time, an essential component of multicentric clinical trials. The annotation system also allowed users to view stereoscopic images that are stereo pairs. This web-based annotation system is useful and valuable in monitoring patient care, in multicentric clinical trials, telemedicine, teaching and routine clinical settings.

A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

PubMed

Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-05-01

Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

PubMed Central

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-01-01

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

PubMed

Lomer, Miranda C E; Grainger, Stephen L; Ede, Roland; Catterall, Adrian P; Greenfield, Simon M; Cowan, Russell E; Vicary, F Robin; Jenkins, Anthony P; Fidler, Helen; Harvey, Rory S; Ellis, Richard; McNair, Alistair; Ainley, Colin C; Thompson, Richard P H; Powell, Jonathan J

2005-03-01

Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey

PubMed Central

Hislop, WS; Follett, EAC; Bouchier, IAD; MacSween, RNM

1981-01-01

In a study of 195 patients derived from five centres in northern Britain and with histologically confirmed alcoholic liver disease we have found an increased prevalence of serological markers of hepatitis B. This increased prevalence was found in each of the five centres; the overall frequency ranged from 11% sero-positivity in fatty liver, 12% in alcoholic hepatitis and 27% in cirrhosis. PMID:7276216

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study.

PubMed

van der Have, Mike; Belderbos, Tim D G; Fidder, Herma H; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P; Eshuis, Emma J; Ponsioen, Cyriel Y; Siersema, Peter D; van Oijen, Martijn G H; Oldenburg, Bas

2014-10-01

Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

PubMed

Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H

2005-01-01

Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

The burden of common skin diseases assessed with the EQ5D™: a European multicentre study in 13 countries.

PubMed

Balieva, F; Kupfer, J; Lien, L; Gieler, U; Finlay, A Y; Tomás-Aragonés, L; Poot, F; Misery, L; Sampogna, F; van Middendorp, H; Halvorsen, J A; Szepietowski, J C; Lvov, A; Marrón, S E; Salek, M S; Dalgard, F J

2017-05-01

Generic instruments measuring health-related quality of life (HRQoL), like EQ5D™, enable comparison of skin diseases with healthy populations and nondermatological medical conditions, as well as calculation of utility data. To measure HRQoL in patients with common skin diseases and healthy controls across Europe using the EQ5D. This multicentre observational cross-sectional study was conducted in 13 European countries. Each dermatology clinic recruited at least 250 consecutive adult outpatients to complete questionnaires, including the EQ5D. There were 5369 participants (4010 patients and 1359 controls). Mean ± SD self-rated health state reported by patients was 69·9 ± 19·7; for controls it was 82·2 ± 15·5. When adjusted for confounding factors, including comorbidity, mean patient EQ visual analogue scores were 10·5 points lower than for controls (standardized β = -0·23). Odds ratio with 95% confidence interval for impairment in all five dimensions of EQ5D adjusted for confounders was doubled for patients compared with controls. Patients with hidradenitis suppurativa (HS), blistering conditions, leg ulcers, psoriasis and eczemas had the highest risk for reduction in HRQoL in most dimensions (2-10-fold). Data on differences of impairment by dimensions offer new insights. This study confirms the large impact skin conditions have on patients' well-being, differentiating between aspects of HRQoL. Patients with HS, blistering diseases, leg ulcers, infections and most chronic skin diseases reported reduced HRQoL compared with patients with chronic obstructive lung disease, diabetes mellitus, cardiovascular disease and cancers. These findings are important in the prioritization of resource allocation between medical fields and within dermatological subspecialities. © 2016 British Association of Dermatologists.

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Elective frozen elephant trunk procedure using the E-Vita Open Plus prosthesis in 94 patients: a multicentre French registry.

PubMed

Verhoye, Jean-Philippe; Belhaj Soulami, Reda; Fouquet, Olivier; Ruggieri, Vito Giovanni; Kaladji, Adrien; Tomasi, Jacques; Sellin, Michel; Farhat, Fadi; Anselmi, Amedeo

2017-10-01

Our goal was to evaluate the operative outcomes of the frozen elephant trunk technique using the E-Vita Open Plus® hybrid prosthesis in chronic aortic arch diseases and report clinical and radiological outcomes at the 1-year follow-up. As determined from a prospective multicentre registry, 94 patients underwent frozen elephant trunk procedures using the E-Vita Open Plus hybrid device for the treatment of chronic aortic conditions, including 50% chronic aortic dissections, 40% degenerative aneurysms and 10% miscellaneous indications. Fifty percent of the cases were reoperations. The perioperative mortality rate was 11.7%. Spinal cord ischaemia and stroke rates were 4% and 9.6%, respectively. The mean cardiopulmonary bypass time was 252 ± 97 min, cardiac ischaemia time was 152 ± 53 min and cerebral perfusion time was 82 ± 22 min. Concomitant procedures were observed in 15% of patients. Among the 83 surviving patients, the survival rate after the 1-year follow-up was 98%. Eleven percent of patients underwent endovascular completion, whereas 4% of patients required aortic reintervention at 1 year. The E-Vita Open Plus hybrid device confirms the favourable short- and mid-term outcomes offered by its predecessor in frozen elephant trunk procedures in patients with chronic aortic arch disease. Implantation of the E-Vita Open Plus is associated with good 1-year survival rates, good rates of favourable aortic remodelling in both chronic dissection and degenerative aneurysms and a reproducible technique in a multicentre registry. Continued follow-up is required due to the risk of evolution at the downstream aorta. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

PubMed

Donat, Ester; Ramos, Jose M; Sánchez-Valverde, Félix; Moreno, Ana; Martinez, Maria-Jose; Leis, Rosaura; Peña-Quintana, Luis; Castillejo, Gemma; Fernández, Sonia; Garcia, Zuriñe; Ortigosa, Luis; Balmaseda, Elena; Marugán, José-Manuel; Eizaguirre, Francisco-Javier; Lorenzo, Helena; Barrio, Josefa; Ribes-Koninckx, Carmen

2016-02-01

A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

The Psoriatic Arthritis Registry of Turkey: results of a multicentre registry on 1081 patients.

PubMed

Kalyoncu, Umut; Bayindir, Özün; Ferhat Öksüz, Mustafa; Doğru, Atalay; Kimyon, Gezmiş; Tarhan, Emine Figen; Erden, Abdulsamet; Yavuz, Şule; Can, Meryem; Çetin, Gözde Yıldırım; Kılıç, Levent; Küçükşahin, Orhan; Omma, Ahmet; Ozisler, Cem; Solmaz, Dilek; Bozkirli, Emine Duygu Ersözlü; Akyol, Lütfi; Pehlevan, Seval Masatlıoğlu; Gunal, Esen Kasapoglu; Arslan, Fatos; Yılmazer, Barış; Atakan, Nilgun; Aydın, Sibel Zehra

2017-02-01

The aim was to assess the characteristics of PsA, find out how well the disease is controlled in real life, demonstrate the treatments and identify the unmet needs. The PsA registry of Turkey is a multicentre Web-based registry established in 2014 and including 32 rheumatology centres. Detailed data regarding demographics for skin and joint disease, disease activity assessments and treatment choices were collected. One thousand and eighty-one patients (64.7% women) with a mean (sd) PsA duration of 5.8 (6.7) years were enrolled. The most frequent type of PsA was polyarticular [437 (40.5%)], followed by oligoarticular [407 (37.7%)] and axial disease [372 (34.4%)]. The mean (sd) swollen and tender joint counts were 1.7 (3) and 3.6 (4.8), respectively. Of these patients, 38.6% were on conventional synthetic DMARD monotherapy, 7.1% were on anti-TNF monotherapy, and 22.5% were using anti-TNF plus conventional synthetic DMARD combinations. According to DAS28, 86 (12.4%) patients had high and 105 (15.2%) had moderate disease activity. Low disease activity was achieved in 317 (45.7%) patients, and 185 (26.7%) were in remission. Minimal disease activity data could be calculated in 247 patients, 105 of whom (42.5%) had minimal disease activity. The major differences among sexes were that women were older and had less frequent axial disease, more fatigue, higher HAQ scores and less remission. The PsA registry of Turkey had similarities with previously published registries, supporting its external validity. The finding that women had more fatigue and worse functioning as well as the high percentage of active disease state highlight the unmet need in treatment of PsA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study.

PubMed

Kudo, Chieko; Shin, Wee Soo; Sasaki, Nobuhiro; Harai, Kazuo; Kato, Kai; Seino, Hiroaki; Goke, Eiji; Fujino, Takemasa; Kuribayashi, Nobuichi; Pearce, Youko Onuki; Taira, Masato; Matsushima, Ryoji; Minabe, Masato; Takashiba, Shogo

2018-01-12

Atherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one of the major causes of death in worldwide. Meanwhile, periodontal disease is a chronic inflammatory disease caused by infection with periodontal pathogens such as P. gingivalis (Porphyromonas gingivalis). Several studies have reported association between periodontal infection and atherosclerosis, but direct investigation about the effects of periodontal treatment on atherosclerosis has not been reported. We have planned Japanese local clinics to determine the relationship between periodontal disease and atherosclerosis under collaborative with medical and dental care. A prospective, multicentre, observational study was conducted including 38 medical patients with lifestyle-related diseases in the stable period under consultation at participating medical clinics and 92 periodontal patients not undergoing medical treatment but who were consulting at participating dental clinics. Systemic and periodontal examinations were performed before and after periodontal treatment. At baseline, LDL-C (low-density lipoprotein cholesterol) levels and percentage (%) of mobile teeth were positively related to plasma IgG (immunoglobulin) antibody titer against P. gingivalis with multivariate analysis. Corresponding to improvements in periodontal clinical parameters after treatment, right and left max IMT (maximum intima-media thickness) levels were decreased significantly after treatment (SPT-S: start of supportive periodontal therapy, SPT-1y: at 1 year under SPT, and SPT-3y: at 3 years under SPT). The present study has clarified our previous univariate analysis results, wherein P. gingivalis infection was positively associated with progression of atherosclerosis. Thus, routine screening using plasma IgG antibody titer against P. gingivalis and periodontal treatment under collaborative with medical and dental care may prevent cardiovascular accidents caused by atherosclerosis.

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

[Sonographically detectable splenic disorders in dogs with malignant lymphoma].

PubMed

Eberhardt, F; Köhler, C; Krastel, D; Winter, K; Alef, M; Kiefer, I

2015-01-01

To evaluate the frequency of different sonographic splenic disorders in dogs with different anatomic forms of malignant lymphoma. Additionally, the occurrence of the moth-eaten pattern in the parenchyma of the spleen in patients with diseases other than lymphoma should be investigated. Retrospective analysis of patient data collected from dogs histologically or cytologically diagnosed with malignant lymphoma and for which ultrasonographic images were available before the initiation of therapy. Patient data from dogs with a moth-eaten pattern within the splenic parenchyma were evaluated separately. Exclusion criterion was the administration of cytostatic agents prior to diagnosis. In 84% of 164 dogs with malignant lymphoma, an altered pattern of the spleen was diagnosed ultrasonographically. Ninety-four of these 137 patients had a moth-eaten pattern of the splenic parenchyma and 43 dogs displayed abnormalities in the form of splenomegaly, coarse echotexture or other changes of the parenchyma. When a moth-eaten pattern was diagnosed, the affected dogs suffered significantly more often from a multicentric lymphoma (95%) than from any other anatomical lymphoma form. Only one dog displayed a moth-eaten pattern of the splenic parenchyma without diagnosis of a malignant lymphoma. The positive predictive value of the moth-eaten pattern for malignant lymphoma was 99% and, in particular, for the multicentric lymphoma this was 95%. In total, 84% of the 164 dogs displayed a multicentric lymphoma, 5% a mediastinal or a cutaneous lymphoma, respectively, 4% a gastrointestinal lymphoma, and one animal had an ocular or renal lymphoma, respectively. Sonographic changes of the spleen are often diagnosed in dogs with malignant lymphoma, independent of the anatomical lymphoma form. When the moth-eaten pattern is observed, it is very likely that the affected dog suffers from a malignant lymphoma, most probably a multicentric lymphoma.

Distinct features distinguishing IgG4-related disease from multicentric Castleman’s disease

PubMed Central

Sasaki, Takanori; Akiyama, Mitsuhiro; Kaneko, Yuko; Mori, Takehiko; Yasuoka, Hidekata; Suzuki, Katsuya; Yamaoka, Kunihiro; Okamoto, Shinichiro; Takeuchi, Tsutomu

2017-01-01

Objectives Differentiating IgG4-related disease (IgG4-RD) from multicentric Castleman’s disease (MCD) is challenging because both diseases present high serum IgG4. The objective of this study is to clarify the differences in characteristics and identify a clinically useful approach to differentiate these two diseases. Methods Forty-five consecutive patients with untreated active IgG4-RD and 33 patients with MCD were included in this study, who visited our institution from January 2000 to August 2016. The clinical and laboratory findings for the patients of the two diseases were compared. Various combinations of the distinctive findings were evaluated to identify the most efficient differentiating features between IgG4-RD and MCD. Results The levels of serum IgG4 were not different between the two diseases. Orbits, lacrimal glands, salivary glands or pancreas were involved in 88.9% of IgG4-RD cases and only in 3.0% of MCD cases. All MCD cases involved lymph nodes. Atopic history was characteristic for IgG4-RD. The levels of C reactive protein (CRP) with a cut-off of 0.80 mg/dL and IgA with a cut-off of 330 mg/dL were the most distinctive. The combination of ‘Orbits, lacrimal glands, salivary glands or pancreas involvement, atopic history, or non-involvement of lymph node’ and ‘CRP ≤ 0.8 mg/dL or IgA ≤ 330 mg/dL’ yielded the probability of 97.8% in IgG4-RD, while that of 3.0 % in patients with MCD. Conclusions Our study revealed distinct features between IgG4-RD and MCD. Differentiating between the diseases based on those distinct features, including distribution of organ involvement, atopic history, levels of IgA and CRP, was a useful approach. PMID:28959455

Kaposi sarcoma–associated herpesvirus: immunobiology, oncogenesis, and therapy

PubMed Central

Dittmer, Dirk P.

2016-01-01

Kaposi sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent underlying Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. This human gammaherpesvirus was discovered in 1994 by Drs. Yuan Chang and Patrick Moore. Today, there are over five thousand publications on KSHV and its associated malignancies. In this article, we review recent and ongoing developments in the KSHV field, including molecular mechanisms of KSHV pathogenesis, clinical aspects of KSHV-associated diseases, and current treatments for cancers associated with this virus. PMID:27584730

Theoretical and experimental consideration of the reactions between VxOy+ and ethylene.

PubMed

Justes, Dina R; Mitrić, Roland; Moore, Nelly A; Bonacić-Koutecký, Vlasta; Castleman, A Welford

2003-05-21

We present joint theoretical and experimental results which provide evidence for the selectivity of V(x)O(y)(+) clusters in reactions toward ethylene due to the charge and different oxidation states of vanadium for different cluster sizes. Density functional calculations were performed on the reactions between V(x)O(y)(+) and ethylene, allowing us to identify the structure-reactivity relationship and to corroborate the experimental results obtained by Castleman and co-workers (Zemski, K. A.; Justes, D. R.; Castleman, A. W., Jr. J. Phys. Chem. A 2001, 105, 10237). The lowest-energy structures for the V(2)O(2)(-)(6)(+) and V(4)O(8)(-)(10)(+) clusters and the V(2)O(3)(-)(6)(+)-C(2)H(4) and V(4)O(10)(+)-C(2)H(4) complexes, as well as the energetics for reactions between ethylene and V(2)O(4)(-)(6)(+) and V(4)O(10)(+) are presented here. The oxygen transfer reaction pathway was determined to be the most energetically favorable one available to V(2)O(5)(+) and V(4)O(10)(+) via a radical-cation mechanism. The association and replacement reaction pathways were found to be the optimal channels for V(2)O(4)(+) and V(2)O(6)(+), respectively. These results are in agreement with the experimental results reported previously. Experiments were also conducted for the reactions between V(2)O(5)(+) and ethylene to include an energetic analysis at increasing pressures. It was found that the addition of energy depleted the production of V(2)O(4)(+), confirming that a more involved reaction rather than a collisional process is responsible for the observed phenomenon. In this contribution we show that investigation of reactions involving gas-phase cationic vanadium oxide clusters with small hydrocarbons is suitable for the identification of reactive centers responsible for selectivity in heterogeneous catalysis.

Effectiveness of disease-specific cognitive–behavioural therapy on depression, anxiety, quality of life and the clinical course of disease in adolescents with inflammatory bowel disease: study protocol of a multicentre randomised controlled trial (HAPPY-IBD)

PubMed Central

van den Brink, Gertrude; Stapersma, Luuk; El Marroun, Hanan; Henrichs, Jens; Szigethy, Eva M; Utens, Elisabeth MWJ; Escher, Johanna C

2016-01-01

Introduction Adolescents with inflammatory bowel disease (IBD) show a higher prevalence of depression and anxiety, compared to youth with other chronic diseases. The inflammation-depression hypothesis might explain this association, and implies that treating depression can decrease intestinal inflammation and improve disease course. The present multicentre randomised controlled trial aims to test the effectiveness of an IBD-specific cognitive–behavioural therapy (CBT) protocol in reducing symptoms of subclinical depression and anxiety, while improving quality of life and disease course in adolescents with IBD. Methods and analysis Adolescents with IBD (10–20 years) from 7 hospitals undergo screening (online questionnaires) for symptoms of depression and anxiety. Those with elevated scores of depression (Child Depression Inventory (CDI) ≥13 or Beck Depression Inventory (BDI) II ≥14) and/or anxiety (Screen for Child Anxiety Related Disorders: boys ≥26, girls ≥30) receive a psychiatric interview. Patients meeting criteria for depressive/anxiety disorders are referred for psychotherapy outside the trial. Patients with elevated (subclinical) symptoms are randomly assigned to medical care-as-usual (CAU; n=50) or CAU plus IBD-specific CBT (n=50). Main outcomes: (1) reduction in depressive and/or anxiety symptoms after 3 months and (2) sustained remission for 12 months. Secondary outcomes: quality of life, psychosocial functioning, treatment adherence. In addition, we will assess inflammatory cytokines in peripheral blood mononuclear cells and whole blood RNA expression profiles. For analysis, multilevel linear models and generalised estimating equations will be used. Ethics and dissemination The Medical Ethics Committee of the Erasmus MC approved this study. If we prove that this CBT improves emotional well-being as well as disease course, implementation is recommended. Trial registration number NCT02265588. PMID:26966551

The surface glycoprotein of a natural feline leukemia virus subgroup A variant, FeLV-945, as a determinant of disease outcome.

PubMed

Bolin, Lisa L; Ahmad, Shamim; Levy, Laura S

2011-10-15

Feline leukemia virus (FeLV) is a natural retrovirus of domestic cats associated with degenerative, proliferative and malignant diseases. Studies of FeLV infection in a cohort of naturally infected cats were undertaken to examine FeLV variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. A unique variant, designated FeLV-945, was identified as the predominant isolate in the cohort and was associated with non-T-cell diseases including multicentric lymphoma. FeLV-945 was assigned to the FeLV-A subgroup based on sequence analysis and receptor utilization, but was shown to differ in sequence from a prototype member of FeLV-A, designated FeLV-A/61E, in the long terminal repeat (LTR) and the surface glycoprotein gene (SU). A unique sequence motif in the FeLV-945 LTR was shown to function as a transcriptional enhancer and to confer a replicative advantage. The FeLV-945 SU protein was observed to differ in sequence as compared to FeLV-A/61E within functional domains known to determine receptor selection and binding. Experimental infection of newborn cats was performed using wild type FeLV-A/61E or recombinant FeLV-A/61E in which the LTR (61E/945L) or LTR and SU (61E/945SL) were exchanged for that of FeLV-945. Infection with either FeLV-A/61E or 61E/945L resulted in T-cell lymphoma of the thymus, although 61E/945L caused disease significantly more rapidly. In contrast, infection with 61E/945SL resulted in the rapid induction of a multicentric lymphoma of B-cell origin, thus recapitulating the outcome of natural infection and implicating FeLV-945 SU as a determinant of disease outcome. Recombinant FeLV-B was detected infrequently and at low levels in multicentric lymphomas, and was thereby not implicated in disease induction. Preliminary studies of receptor interaction indicated that virus particles bearing FeLV-945 SU bind to the FeLV-A receptor more efficiently than do particles bearing FeLV-A/61E SU, and that soluble SU proteins expressed from the viruses demonstrate the same differential binding phenotype. Preliminary mutational analysis of FeLV-945 was performed by exchanging regions containing either the primary receptor binding determinant, VRA, the secondary determinant, VRB, or a proline-rich region, PRR, with that of FeLV-A/61E. Results implicated a region containing VRA as a minor contributor, while a region containing VRB largely conferred increased binding efficiency. Copyright © 2011 Elsevier B.V. All rights reserved.

Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial

PubMed Central

2014-01-01

Background Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness. Methods/Design This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated. Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease. Trial registration ClinicalTrials.gov identifier: NCT01547611 PMID:24502414

Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

PubMed

Kubo, Satoshi; Yamaoka, Kunihiro; Amano, Koichi; Nagano, Shuji; Tohma, Shigeto; Suematsu, Eiichi; Nagasawa, Hayato; Iwata, Kanako; Tanaka, Yoshiya

2017-08-01

To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

PubMed

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

PubMed

Amiot, A; Serrero, M; Peyrin-Biroulet, L; Filippi, J; Pariente, B; Roblin, X; Buisson, A; Stefanescu, C; Trang-Poisson, C; Altwegg, R; Marteau, P; Vaysse, T; Bourrier, A; Nancey, S; Laharie, D; Allez, M; Savoye, G; Moreau, J; Vuitton, L; Viennot, S; Aubourg, A; Pelletier, A-L; Bouguen, G; Abitbol, V; Gagniere, C; Bouhnik, Y

2017-08-01

We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD. © 2017 John Wiley & Sons Ltd.

Landforms of the conterminous United States: a digital shaded-relief portrayal

USGS Publications Warehouse

Thelin, Gail P.; Pike, Richard J.

1991-01-01

Our map was made by digital image-processing, a technical specialty related to the broader fields of computer graphics and machine vision (Dawson, 1987; Kennie and McLaren, 1988). The technology includes the many spacially based operations first brought together and developed systematically to manipulate Ranger, Mariner, Landsat, and other images that are reassembled from spacecraft telemetry in a raster or scan-line arrangement of square-grid elements (Nathan, 1966; Castleman, 1979; Sheldon, 1987). These computer procedures have been successfully transferred to landform analysis from remote-sensing applications by substituting terrain heights or sea-floor depths for the customary values of electromagnetic radiation obtained from satellites an stored in digital arrays of pixels (Batson and others, 1975).

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

PubMed

Falivene, S; Pezzulla, D; Di Franco, R; Giugliano, F M; Esposito, E; Scoglio, C; Amato, B; Borzillo, V; D'Aiuto, M; Muto, P

2017-02-01

Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

Sphingomyelin lipidosis (Niemann-Pick disease) in a juvenile raccoon (Procyon lotor).

PubMed

Vapniarsky, N; Wenger, D A; Scheenstra, D; Mete, A

2013-01-01

A wild caught juvenile male raccoon with neurological disease was humanely destroyed due to poor prognosis. Necropsy examination revealed hepatomegaly, splenomegaly and multicentric lymphadenomegaly with diffuse hepatic pallor and pulmonary consolidation with pinpoint pale subpleural foci. Microscopically, there was marked pale cytoplasmic swelling of the central and peripheral neurons as well as the glial cells in the brain, accompanied by multiorgan infiltration by abundant foamy macrophages. Ultrastructural investigation revealed accumulation of concentrically arranged lamellar material within lysosomes of the affected neurons, macrophages and endothelial cells. Biochemical enzymatic analysis detected sphingomyelinase deficiency and lysosomal storage disease consistent with sphingomyelin lipidosis (Niemann-Pick disease [NPD]) was diagnosed. This is the first report of NPD in a raccoon. Copyright © 2013 Elsevier Ltd. All rights reserved.

Juvenile dermatomyositis: new insights and new treatment strategies

PubMed Central

Martin, Neil; Li, Charles K.

2012-01-01

Juvenile dermatomyositis (JDM) is a rare but complex and potentially life-threatening autoimmune disease of childhood, primarily affecting proximal muscles and skin. Although the cause of JDM remains unknown it is clear that genetic and environmental influences play a role in the aetiology. In contrast to adults with dermatomyositis, children with JDM are more likely to have complications that are thought to indicate a vasculopathic process, such as severe skin disease, with ulceration or calcinosis, gut vasculopathy or central nervous system disease. New treatments are much needed and are becoming available and being tested through international multicentre trials. This review will focus on recent insights into pathogenesis, the assessment of the disease in children and the modern approach to its treatment. PMID:22870494

Multicentric myelolipoma in a dog.

PubMed

Kamiie, Junichi; Fueki, Keisuke; Amagai, Harumi; Ichikawa, Youichiro; Shirota, Kinji

2009-03-01

We report herein a case of multicentric myelolipoma in an 11-year-old beagle dog that presented with vomiting. Laparotomy demonstrated the presence of a large mass adherent to the greater omentum and multiple small white maculae in the spleen. Cytological and histological examinations revealed that the mass and maculae comprised mature adipocytes and hematopoietic elements including granulocytic, erythrocytic and megakaryocytic series in several phases of maturation and macrophages containing hemosiderin deposits, resembling bone marrow. Multicentric myelolipoma was diagnosed. This is first report of multicentric myelolipoma in a dog.

The self-assessed psychological comorbidities of prurigo in European patients: A multi-centre study in 13 countries.

PubMed

Brenaut, Emilie; Halvorsen, Jon Anders; Dalgard, Florence J; Lien, Lars; Balieva, Flora; Sampogna, Francesca; Linder, Dennis; Evers, Andrea W M; Jemec, Gregor B E; Gieler, Uwe; Szepietowski, Jacek; Poot, Françoise; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Szabo, Csanad; Lvov, Andrey; Marron, Servando E; Tomas-Aragones, Lucia; Kupfer, Jörg; Misery, Laurent

2018-06-19

Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. The aim of this study was to assess the psychological burden of prurigo in patients of European countries. In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10/27 (37%) suffered from anxiety and 8/27 (29%) from depression. Suicidal ideation was reported by 5/27 (19%) of patients, and for 4 out of these 5 patients, suicidal ideation was related to their skin disease. These frequencies were higher than in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers for example). The impact on quality of life was severe, with a mean DLQI of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

PubMed

Löfdahl, C G; Postma, D S; Laitinen, L A; Ohlsson, S V; Pauwels, R A; Pride, N B

1998-03-01

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

Value of Additional Digital Breast Tomosynthesis for Preoperative Staging of Breast Cancer in Dense Breasts.

PubMed

Krammer, Julia; Stepniewski, Kathrin; Kaiser, Clemens G; Brade, Joachim; Riffel, Philipp; Schoenberg, Stefan O; Wasser, Klaus

2017-09-01

This retrospective study was initiated to determine the diagnostic value of additional preoperative breast tomosynthesis (DBT) for breast cancer staging in dense breasts. Sixty-six patients (69 breasts) with findings of American College of Radiology category 3 or 4 with Breast Imaging Reporting and Data System 5, 6 or 0 were included. All patients underwent digital mammography and additional DBT. A total of 40/69 (58%) cancers were detected on both mammography and DBT, 23 (33.3%) were only seen on DBT (p=0.0001); 6/69 (8.7%) carcinomas were not detected by either method, of which three were invasive lobular carcinomas. Sensitivity for multifocal/multicentric disease was significantly higher on DBT (12/19, 63.2%) compared to mammography (4/19, 21.1%) (p=0.02), specificity was comparable (96.0% vs. 90.0%). Multifocal/multicentric disease was not detected on mammography nor DBT in 7/19 (36.8%) patients, including three invasive lobular carcinomas. DBT may significantly improve preoperative breast cancer staging in patients with dense breasts compared to conventional mammography alone. Nevertheless, limitations have to be expected in the case of invasive lobular carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Ethics and privacy issues of a practice-based surveillance system: need for a national-level institutional research ethics board and consent standards.

PubMed

Kotecha, Jyoti A; Manca, Donna; Lambert-Lanning, Anita; Keshavjee, Karim; Drummond, Neil; Godwin, Marshall; Greiver, Michelle; Putnam, Wayne; Lussier, Marie-Thérèse; Birtwhistle, Richard

2011-10-01

To describe the challenges the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) experienced with institutional research ethics boards (IREBs) when seeking approvals across jurisdictions and to provide recommendations for overcoming challenges of ethical review for multisite and multijurisdictional surveillance and research. The CPCSSN project collects and validates longitudinal primary care health information (relating to hypertension, diabetes, depression, chronic obstructive lung disease, and osteoarthritis) from electronic medical records across Canada. Privacy and data storage security policies and processes have been developed to protect participants' privacy and confidentiality, and IREB approval is obtained in each participating jurisdiction. Inconsistent interpretation and application of privacy and ethical issues by IREBs delays and impedes research programs that could better inform us about chronic disease. The CPCSSN project's experience with gaining approval from IREBs highlights the difficulty of conducting pan-Canadian health surveillance and multicentre research. Inconsistent IREB approvals to waive explicit individual informed consent produced particular challenges for researchers. The CPCSSN experience highlights the need to develop a better process for researchers to obtain timely and consistent IREB approvals for multicentre surveillance and research. We suggest developing a specialized, national, centralized IREB responsible for approving multisite studies related to population health research.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) with cranial vault plasmocytoma and the role of surgery in its management: a case report.

PubMed

Plata Bello, Julio; Garcia-Marin, Victor

2013-10-18

POEMS syndrome (an acronym of polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) is a paraneoplastic disorder related to an underlying plasma cell dyscrasia. The development of such a syndrome is rare and its association with calvarial plasmocytoma is even less common, with only two previous reported cases. We describe, in detail, an unusual presentation of cranial plasmocytoma associated with POEMS syndrome and briefly discuss the possible role of surgery in the management of this disease. We present the case of a 45-year-old Caucasian man who was admitted to our department presenting with progressive weakness in his lower limbs, enlarged lymph nodes and a large mass on the scalp with intense bone erosion. POEMS criteria were present and pathological studies confirmed a Castleman's variant plasmocytoma. Clinical status improved noticeably after the excision of the plasmocytoma and the treatment was completed with radiotherapy and steroid pulse therapy. Cranial vault plasmocytoma and its association with POEMS syndrome are rare conditions with few previously reported cases. Although the role of surgery is not clearly defined in POEMS syndrome guidelines, the fact that there seems to be a better prognosis and clinical outcome when surgery is used as a part of the management in POEMS syndrome with cranial vault plasmocytoma is worth discussing.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

PubMed

Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

2011-03-01

This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Usefulness of a centralized system of data collection for the development of an international multicentre registry of spondyloarthritis

PubMed Central

Schiotis, Ruxandra; Font, Pilar; Zarco, Pedro; Almodovar, Raquel; Gratacós, Jordi; Mulero, Juan; Juanola, Xavier; Montilla, Carlos; Moreno, Estefanía; Ariza Ariza, Rafael; Collantes-Estevez, Eduardo

2011-01-01

Objective. To present the usefulness of a centralized system of data collection for the development of an international multicentre registry of SpA. Method. The originality of this registry consists in the creation of a virtual network of researchers in a computerized Internet database. From its conception, the registry was meant to be a dynamic acquiring system. Results. REGISPONSER has two developing phases (Conception and Universalization) and gathers several evolving secondary projects (REGISPONSER-EARLY, REGISPONSER-AS, ESPERANZA and RESPONDIA). Each sub-project answered the necessity of having more specific and complete data of the patients even from the onset of the disease so, in the end, obtaining a well-defined picture of SpAs spectrum in the Spanish population. Conclusion. REGISPONSER is the first dynamic SpA database composed of cohorts with a significant number of patients distributed by specific diagnosis, which provides basic specific information of the sub-cohorts useful for patients’ evaluation in rheumatology ambulatory consulting. PMID:20823095

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

[Multicentric inflammatory pseudotumor with asynchronic presentation in meninges, liver, spleen and lymph nodes in a patient with seronegative spondiloarthropathy. Case report and review of the literature].

PubMed

Vicuña-González, R M; Rivera-Salgado, M I; García-Velarde, P M Pasquel; de León-Bojorge, B; Ortiz-Hidalgo, C

Inflammatory pseudotumor is a reactive process in which the etiology and pathogenesis are not well defined, that can be found in any location. The cases with central nervous system affection have been described in meninges, brain, choroid plexus and cranial and spinal nerves. Multicentric cases, synchronous and asynchronous have been described. A 45 years-old woman with a rheumatologic disease (a seronegative spondiloarthropathy) who developed an inflammatory pseudotumor in spleen, liver and abdominal lymph nodes in 1995, associated to fever of unknown origin, six years later she presented with an inflammatory pseudotumor of the meninges in the convexity of the right frontoparietal region, with fever, malaise, and increase of globular sedimentation rate, microcytic hypochromic anemia and thrombocytosis. The clinicopathologic features of this lesion are revised, including the different theories in regard to the etiology and pathogenesis, and the role of cytokines produced by inflammatory cells in the tumor.

The medical value and cost-effectiveness of an exercise test for sport preparticipation evaluation in asymptomatic middle-aged white male and female athletes.

PubMed

Chevalier, Laurent; Kervio, Gaelle; Doutreleau, Stephane; Mathieu, Jean-Philippe; Guy, Jean-Michel; Mignot, Aude; Corneloup, Luc; Passard, François; Laporte, Thierry; Girard-Girod, Aude; Hennebert, Olivier; Bernadet, Philippe; Vincent-Chevalier, Marie-Pierre; Gencel, Laurent; Carré, François

2017-03-01

Cardiovascular events related to high-intensity sport practice are rare but dramatic. Coronary artery disease (CAD) is the leading cause of these events after the age of 35 years. The value of a maximal exercise test (ET) for detection of athletes at risk remains a matter of debate. The aim of this prospective multicentre study was to clarify the medical value and cost-effectiveness of an ET in middle-aged white asymptomatic athletes who participate in high-intensity sport. All athletes had a physical examination, assessment of cardiovascular risk factors, a resting electrocardiogram and an ET. In case of abnormal ET, complementary cardiovascular evaluation was performed, when requested, to detect potential cardiovascular disease. 1361 asymptomatic athletes (mean age 50.4±9.6 years; mean training 5.1±3.2h/week; 10.4% women) with a normal resting electrocardiogram and without cardiovascular disease were consecutively included. An abnormal ET was reported in 144 subjects (94% men); this was positively related to the subject's age and cardiovascular risk level. Cardiac arrhythmias (48%) and CAD symptoms (33.3%) were mainly reported. Cardiovascular disease was confirmed in 24 cases (1.7% from the whole population; 16.7% from those with an abnormal ET) - mainly CAD (n=12) and arterial hypertension (n=8). Seventy athletes presented significant unexplained arrhythmias. The cost was approximately €8450 for every confirmed case of cardiovascular disease. In this multicentre study in middle-aged athletes, a systematic ET was abnormal in 10.6% of cases. About 2% of subjects had cardiovascular disease, mainly arrhythmias and CAD. From these results, it seems that in a trained population aged >35 years, ET should be targeted at men with at least two cardiovascular risk factors, with acceptable cost-effectiveness. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

PubMed

Carrion, Flavio A; Figueroa, Fernando E

2011-05-11

Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemic lupus erythematosus. The impressive results of these uncontrolled phase I and II trials - mostly in patients with non-responding renal disease - point to the need to perform controlled multicentric trials. In addition, they suggest that there is much to be learned from the basic and clinical science of MSCs in order to reap the full potential of these multifaceted progenitor cells in the treatment of autoimmune diseases.

[Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

PubMed

Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

2000-08-12

The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project.

PubMed

Prior, Nieves; Remor, Eduardo; Gómez-Traseira, Carmen; López-Serrano, Concepción; Cabañas, Rosario; Contreras, Javier; Campos, Ángel; Cardona, Victoria; Cimbollek, Stefan; González-Quevedo, Teresa; Guilarte, Mar; de Rojas, Dolores Hernández Fernández; Marcos, Carmen; Rubio, María; Tejedor-Alonso, Miguel Ángel; Caballero, Teresa

2012-07-20

There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.

Healthcare use, costs and quality of life in patients with end-stage kidney disease receiving conservative management: results from a multi-centre observational study (PACKS).

PubMed

Phair, Glenn; Agus, Ashley; Normand, Charles; Brazil, Kevin; Burns, Aine; Roderick, Paul; Maxwell, Alexander P; Thompson, Colin; Yaqoob, Magdi; Noble, Helen

2018-05-01

Previous research has explored the cost of providing renal replacement therapies in patients with end-stage kidney disease and their quality of life. This is the first study to examine the healthcare costs of patients receiving conservative care without dialysis for end-stage kidney disease. This alternative to dialysis is an option for patients who prefer a supportive and palliative care approach. Descriptive cost and quality of life analyses alongside a UK-based multi-centre observational study in patients receiving conservative management for end-stage kidney disease. Health service use was recorded up to 12 months after making the decision to receive conservative management. Mean costs were calculated for each 3-month time period. The annual cost was calculated in two ways: by using only patients with complete cost data and by using all available data weighted by the number of patients at each time point. In total, 42 patients who opted for conservative management over dialysis were recruited. Mean costs were £1622 (0-3 months), £1008 (3-6 months), £554 (6-9 months) and £2626 (9-12 months). Mean annual cost based on complete data ( n = 8) was £5511, and the weighted mean annual cost was £5620. The importance of this study is twofold. First, it provides substantive new information for health and social care planning of conservative management by demonstrating where demand exists for services, in both the United Kingdom and other countries with a comparable health service structure. Second, methodologically, it indicates that it is feasible to collect service use data directly from this patient population.

Doppler-guided transanal haemorrhoidal dearterialization for haemorrhoids: results from a multicentre trial.

PubMed

Ratto, C; Parello, A; Veronese, E; Cudazzo, E; D'Agostino, E; Pagano, C; Cavazzoni, E; Brugnano, L; Litta, F

2015-01-01

This multicentre study, based on the largest patient population ever published, aims to evaluate the efficacy of Doppler-guided transanal haemorrhoidal dearterialization (THD Doppler) in the treatment of symptomatic haemorrhoids and to identify the factors predicting failure for an effective mid-term outcome. Eight hundred and three patients affected by Grade II (137, 17.1%), III (548, 68.2%) and IV (118, 14.7%) symptomatic haemorrhoidal disease underwent THD Doppler, with a rectal mucopexy in patients with haemorrhoidal prolapse. The disease was assessed through a specifically designed symptom questionnaire and scoring system. A uni- and multivariate analyses of the potential predictive factors for failure were performed. The morbidity rate was 18.0%, represented mainly by pain or tenesmus (106 patients, 13.0%). Acute bleeding requiring surgical haemostasis occurred in seven patients (0.9%). No serious or life-threatening complications occurred. After a mean follow-up period of 11.1 ± 9.2 months, the overall success rate was 90.7% (728 patients), with a recurrence of haemorrhoidal prolapse, bleeding, and both symptoms in 51 (6.3%), 19 (2.4%) and 5 (0.6%) patients, respectively. Sixteen out of 47 patients undergoing re-operation had a conventional haemorrhoidectomy. All the symptoms were significantly improved in each domain of the score (P < 0.0001). At multivariate analysis the absence of morbidity and performance of a distal Doppler-guided dearterialization were associated with a better outcome. THD Doppler is a safe and effective therapy for haemorrhoidal disease. If this technique is to be employed, an accurate distal Doppler-guided dearterialization and a tailored mucopexy are mandatory to contain and reduce the symptoms. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Vedolizumab in Paediatric Inflammatory Bowel Disease: A Retrospective Multi-Centre Experience From the Paediatric IBD Porto Group of ESPGHAN.

PubMed

Ledder, Oren; Assa, Amit; Levine, Arie; Escher, Johanna C; de Ridder, Lissy; Ruemmele, Frank; Shah, Neil; Shaoul, Ron; Wolters, Victorien M; Rodrigues, Astor; Uhlig, Holm H; Posovsky, Carsten; Kolho, Kaija-Leena; Jakobsen, Christian; Cohen, Shlomi; Shouval, Dror S; de Meij, Tim; Martin-de-Carpi, Javier; Richmond, Lisa; Bronsky, Jiri; Friedman, Mira; Turner, Dan

2017-10-01

Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Retrospective review of children [aged 2-18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14-38; range 6-116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn's disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen.

PubMed Central

Delsol, G.; Meggetto, F.; Brousset, P.; Cohen-Knafo, E.; al Saati, T.; Rochaix, P.; Gorguet, B.; Rubin, B.; Voigt, J. J.; Chittal, S.

1993-01-01

Based on observations of 66 cases, in which tissues were specially processed to optimize the simultaneous preservation of cell membrane antigens and morphology, we provide evidence in favor of a relationship between follicular dendritic reticulum cells (FDRC) and Reed-Sternberg (RS) cells of Hodgkin's disease (HD) other than the lymphocyte predominance subtype. RS cells were intimately related to the FDRC network (75% of cases), and the expression of CD21 antigen was frequent (41% of cases). Exclusive expression of CD21 antigen was found in 11 cases of HD, while the expression of other B-cell-associated markers (CD19, CD20, CD22) was both variable and inconsistent. The expression of T-cell antigens (CD3, CD4, CD8) was rare. Null phenotype of RS cells was observed in 27 of 66 cases (41%). Epstein-Barr virus (EBV) nucleic acids were found in 34 of 66 (51.5%) cases. Double labeling techniques showed the presence of EBV-positive RS cells within the FDRC network. A non-B-cell origin of RS cells was supported by the differential expression of EBV latent antigens in HD (latent membrane protein+, EB nuclear antigen 2-), which is unusual in EBV-driven lymphoblastoid cell lines and EBV-positive B-cell lymphomas. FDRC and RS cells are known to share morphological traits (binucleated cells), and both cell types possess Fc receptor for IgG. The hypothesis is further backed by the findings of CD15 antigen expression by occasional RS-like dysplastic FDRC in Castleman's disease (five cases), which is characterized by hyperplasia of FDRC. Whether FDRC might be the only cells involved in the conversion to RS cells by the loss or gain of antigens remains to be determined. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7685151

Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma

PubMed Central

Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma'ayan, Avi; Nam, Do-Hyun

2016-01-01

We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID:26863628

Pediatric Inflammatory Bowel Disease.

PubMed

Kapoor, Akshay; Bhatia, Vidyut; Sibal, Anupam

2016-11-15

The incidence of inflammatory bowel disease is increasing in the pediatric population worldwide. There is paucity of high quality scientific data regarding pediatric inflammatory bowel disease. Most of the guidelines are offshoots of work done in adults, which have been adapted over time to diagnose and treat pediatric patients. This is in part related to the small numbers in pediatric inflammatory bowel disease and less extensive collaboration for multicentric trials both nationally and internationally. A literature search was performed using electronic databases i.e. Pubmed and OVID, using keywords: pediatric, inflammatory bowel disease, Crohns disease, Ulcerative colitis, epidemiology and guidelines. This article amalgamates the broad principles of diagnosing and managing a child with suspected inflammatory bowel disease. 25% of the patients with inflammatory bowel disease are children and and young adolescents. The primary concern is its impact on growth velocity, puberty and quality of life, including psychosocial issues. Treatment guidelines are being re-defined as the drug armamentarium is increasing. The emphasis will be to achieve mucosal healing and normal growth velocity with minimal drug toxicity.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

PubMed

Leung, D Y M; Hanifin, J M; Pariser, D M; Barber, K A; Langley, R G; Schlievert, P M; Abrams, B; Hultsch, T

2009-08-01

Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design.

PubMed

Kelly, Damian J; McCann, Gerald P; Blackman, Daniel; Curzen, Nicholas P; Dalby, Miles; Greenwood, John P; Fairbrother, Kathryn; Shipley, Lorraine; Kelion, Andrew; Heatherington, Simon; Khan, Jamal N; Nazir, Sheraz; Alahmar, Albert; Flather, Marcus; Swanton, Howard; Schofield, Peter; Gunning, Mark; Hall, Roger; Gershlick, Anthony H

2013-02-22

Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study.

PubMed

Hsu, L Y; Lee, D G; Yeh, S P; Bhurani, D; Khanh, B Q; Low, C Y; Norasetthada, L; Chan, T; Kwong, Y L; Vaid, A K; Alejandria, I; Mendoza, M; Chen, C Y; Johnson, A; Tan, T Y

2015-06-01

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

PubMed Central

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-01-01

Introduction This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. Trial registration number EUDRACT Reference Number: 2012-002764-27. PMID:25300460

Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study.

PubMed

Lorusso, Roberto; Gelsomino, Sandro; De Cicco, Giuseppe; Beghi, Cesare; Russo, Claudio; De Bonis, Michele; Colli, Andrea; Sala, Andrea

2008-04-01

To evaluate postoperative outcome of emergency surgery for acute severe mitral regurgitation (ASMR) from a multicentre experience. In six centres, 279 patients (mean age 62+/-14 years, 62% female) undergoing emergency surgery for ASMR from December 1986 to March 2007 were analysed and followed up. Aetiology included acute myocardial infarction (AMI) in 126 patients (group 1, 45%), degenerative mitral valve disease in 74 (group 2, 26%), and acute endocarditis (AE) in 79 (group 3, 28%). Preoperatively, all patients were in haemodynamic instability, with 185 patients in cardiogenic shock (66%), 184 (66%) intubated, and 61 (22%) on IABP, respectively. Valve repair was performed in 76 (27%), whereas 203 (73%) underwent valve replacement. Median follow-up (98% complete) was 70.8 months (inter-quartile range 59.8-86.66 months). Overall 30-day mortality was 22.5% (63/279). Early death was significantly lower in group 2 (p<0.001 and p=0.005 vs group 1 and 3, respectively) whereas no difference was detected between group 1 and 3. At logistic regression analysis AMI, AE, shock, left ventricular dysfunction, and coronary artery disease were predictors of early death. Overall 15-year survival was 67+/-10%. Survival was lower in group 1 (39+/-11%) than in group 2 (75+/-9%) and group 3 (77+/-10%). Cox regression found AMI, and associated coronary artery disease to be predictors of late death. Overall 15-year actuarial and actual freedom from cardiac-related events were 44+/-9% and 28+/-10%, respectively, with the worst outcome in the presence of AE. Associated coronary artery disease, AE, AMI, preoperative atrial fibrillation, and chronic renal failure were independent predictors of cardiac-related events. Emergency surgery for ASMR remains a surgical challenge for high incidence of early and late cardiac-related events, particularly in patients with associated coronary artery disease and acute endocarditis. Apparently, type of mitral valve surgical approaches (repair or replacement) did not provide any influence on postoperative outcome.

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study.

PubMed

Brossard, Philippe; Boulvain, Michel; Coll, Oriol; Barlow, Patricia; Aebi-Popp, Karoline; Bischof, Paul; Martinez de Tejada, Begoña

2008-10-01

To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

Epidemiological multicentre study on the education provided to patients with type 2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.

PubMed

García-Donaire, J A; Franch-Nadal, J; Rodríguez-Fortúnez, P; Labrador-Barba, E; Orera-Peña, M L; Rodríguez de Miguel, M

The purpose of the present study was to characterize the education that patients with type 2 diabetes mellitus receive, and to identify differences as regards the presence of insulin therapy or not. This crossover, multicentre and descriptive study involved 1066 Spanish physicians who completed a questionnaire on Internet. The physicians that responded had a mean of 26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in an urban area. Physicians rated the level of patient knowledge about their disease on a 5.0 point-scale. Fifty percent of them indicated that they spent between 15 and 30min in educating patients at the time of diagnosis. Previous control with HbA1c>9%, presence of microvascular complications, and a low socio-cultural level, were factors associated with spending more time in education. This is the first study designed to evaluate the education provided to patients with type 2 diabetes mellitus from Spain. The time spent and the individualization of the education are important factors associated with better long-term control of the disease, and thus with the effectiveness of the clinical management. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Czech multicenter research database of severe COPD

PubMed Central

Novotna, Barbora; Koblizek, Vladimir; Zatloukal, Jaromir; Plutinsky, Marek; Hejduk, Karel; Zbozinkova, Zuzana; Jarkovsky, Jiri; Sobotik, Ondrej; Dvorak, Tomas; Safranek, Petr

2014-01-01

Purpose Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. Patients and methods The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. Results The objective of this paper was to outline the methodology of this study. Conclusion The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic. PMID:25419124

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

PubMed

Langner, Cord; Schneider, Nora I; Plieschnegger, Wolfgang; Schmack, Bertram; Bordel, Hartmut; Höfler, Bernd; Eherer, Andreas J; Wolf, Eva-Maria; Rehak, Peter; Vieth, Michael

2014-07-01

The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P < 0.001) indicative of GORD, intestinal metaplasia (P < 0.001), and an endoscopic diagnosis of oesophagitis (P < 0.001). No association with an endoscopic diagnosis of Barrett's oesophagus or with gastric pathology, particularly Helicobacter infection, was observed. Cardiac mucosa is a common finding in biopsy specimens taken from the gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion. © 2014 John Wiley & Sons Ltd.

Multicentre imaging measurements for oncology and in the brain

PubMed Central

Tofts, P S; Collins, D J

2011-01-01

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (<2–3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T1, diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. PMID:22433831

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

Notch2 transduction by feline leukemia virus in a naturally infected cat.

PubMed

Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

2014-04-01

Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The new system of review by multicentre research ethics committees: prospective study

PubMed Central

Tully, Joanna; Ninis, Nelly; Booy, Robert; Viner, Russell

2000-01-01

Objective To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. Design Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. Setting A single multicentre research ethics committee and 125 local ethics committees from six regions of England. Main outcome measures Time to reply, time to approval, and number of non-local changes to the application requested. Results Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. Conclusions The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. PMID:10784541

Micrometastases in neuroblastoma: are they clinically important?

PubMed Central

Burchill, S A

2004-01-01

Despite advances in the treatment of neuroblastoma (NBL), recurrence and metastases continue to pose major problems in clinical management. The relation between micrometastases and the development of secondary disease is not fully understood. However, accurate methods to detect low numbers of tumour cells may allow the evaluation of their role in the disease process, and by implication the possible benefits of eliminating them. Although there is substantial evidence for the increased sensitivity of current molecular methods for the detection of NBL cells compared with more conventional cytology, the clinical relevance and usefulness of detecting this disease remain controversial. The primary goal of current translational research must be to evaluate the clinical relevance of micrometastatic disease detected by these methods in multicentre prospective clinical outcome studies. Only then can the clinical usefulness of these methods be defined so that they may be introduced into relevant clinical practice. PMID:14693828

A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

PubMed

Watson, Angus J M; Bruhn, Hanne; MacLeod, Kathleen; McDonald, Alison; McPherson, Gladys; Kilonzo, Mary; Norrie, John; Loudon, Malcolm A; McCormack, Kirsty; Buckley, Brian; Brown, Steven; Curran, Finlay; Jayne, David; Rajagopal, Ramesh; Cook, Jonathan A

2014-11-11

Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

Frequent coexistence of chronic heart failure and chronic obstructive pulmonary disease in respiratory and cardiac outpatients: Evidence from SUSPIRIUM, a multicentre Italian survey.

PubMed

Griffo, Raffaele; Spanevello, Antonio; Temporelli, Pier Luigi; Faggiano, Pompilio; Carone, Mauro; Magni, Giovanna; Ambrosino, Nicolino; Tavazzi, Luigi

2017-04-01

Background Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) frequently coexist but concurrent COPD + CHF has been little investigated. Design This multicentre survey (SUSPIRIUM) was designed to evaluate: the prevalence of COPD in stable CHF and CHF in stable COPD; diagnostic/therapeutic work-up for concurrent COPD + CHF; clinical profile of patients with COPD + CHF; predictors of COPD in CHF and CHF in COPD. Methods A 5-month-long cross-sectional prospective observational survey was conducted in 10 cardiac and 10 respiratory connected outpatient units. Results The prevalence of CHF in the 378 surveyed COPD patients was 11.9% (95% confidence interval 8.8-16.6) and the prevalence of COPD in 375 CHF patients was 31.5% (95% confidence interval 26.8-36.4). Diagnostic tests for suspected comorbidity were prescribed in 21.6% and 22.9% of COPD and CHF patients, respectively. Patients with coexisting CHF + COPD had a higher incidence of hypertension, physical inactivity and more frequently a GOLD score of 3 or greater. Compared to CHF only, CHF + COPD patients were significantly older, more frequently smokers, at worse respiratory risk and in a higher New York Heart Association class. Conversely, hypercholesterolaemia, a family history of ischaemic heart disease, fluid retention and comorbidities were more frequent in COPD + CHF than COPD-only patients. At multivariate analysis, a GOLD score of 3 or greater in CHF strongly predicted coexistent COPD (odds ratio 8.985, P < 0.0001) as did a history of other respiratory diseases (5.184, P < 0.0001). A history of ischaemic heart disease (4.868, P < 0.0001), atrial fibrillation (3.302, P < 0.0001) and sedentary lifestyle (2.814, P < 0.004) predicted coexistent CHF in COPD. Conclusion The high prevalence of COPD + CHF calls for integrated disease management between cardiologists and pulmonologists. SUSPIRIUM identifies which cardiac/pulmonary outpatients should be screened for the respective comorbidity.

Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.

PubMed

Merrill, Joan T; Wallace, Daniel J; Petri, Michelle; Kirou, Kyriakos A; Yao, Yihong; White, Wendy I; Robbie, Gabriel; Levin, Robert; Berney, Seth M; Chindalore, Vishala; Olsen, Nancy; Richman, Laura; Le, Chenxiong; Jallal, Bahija; White, Barbara

2011-11-01

Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets. Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE. received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days. Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014). Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease.

PubMed

Hussain, Shazia T; Paul, Matthias; Plein, Sven; McCann, Gerry P; Shah, Ajay M; Marber, Michael S; Chiribiri, Amedeo; Morton, Geraint; Redwood, Simon; MacCarthy, Philip; Schuster, Andreas; Ishida, Masaki; Westwood, Mark A; Perera, Divaka; Nagel, Eike

2012-09-19

In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation. The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807. MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

PubMed

Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

2009-09-19

Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

Characteristics of patients with rheumatoid arthritis presenting for physiotherapy management: a multicentre study.

PubMed

Kennedy, Norelee; Keogan, Fiona; Fitzpatrick, Martina; Cussen, Grainne; Wallace, Lorraine

2007-03-01

To describe the characteristics of patients with rheumatoid arthritis (RA) attending for physiotherapy management in Ireland. Managers of physiotherapy departments in the 53 hospitals in Ireland were invited to participate in a multi-centre observational study over a 6-month period. Data on patients with RA the day of presentation for physiotherapy management were recorded. These data related to patient demographic details, disease management, aids and appliances, splint and orthoses usage and occupational issues. The Health Assessment Questionnaire was also recorded for each patient. A total of 273 patients from eight physiotherapy departments participated in the survey (n = 199; 73% female). Mean age of the participants was 59.3 (SD 12.5) years with mean disease duration of 13.8 (SD 10.6) years. The majority of the patients were inpatients (n = 170, 62%). Sixty-eight per cent of patients had attended for previous physiotherapy treatment and 98% were under current rheumatologist care. Biologic therapies were prescribed to 11% of patients. Use of splint and foot orthoses was high with 133 patients (49%) wearing splints and 75 (31%) wearing foot orthoses. The majority of patients had moderate (n = 119, 44%) or severe (n = 94, 35%) disability as per Health Assessment Questionnaire (HAQ) score. Mean HAQ score was 1.5, with HAQ scores showing increasing disability with increasing age, disease duration and erythrocyte sedimentation rate (ESR) levels. Patients with RA attending for physiotherapy management present with varied profiles. This study provides valuable information on the characteristics of patients with RA attending for physiotherapy management which will contribute to physiotherapy service planning and delivery and will optimize patient care.

Technetium-99m tetrofosmin rest/stress myocardial SPET with a same-day 2-hour protocol: comparison with coronary angiography. A Spanish-Portuguese multicentre clinical trial.

PubMed

Montz, R; Perez-Castejón, M J; Jurado, J A; Martín-Comín, J; Esplugues, E; Salgado, L; Ventosa, A; Cantinho, G; Sá, E P; Fonseca, A T; Vieira, M R

1996-06-01

Technetium-99m tetrofosmin (Myoview) has unique properties for myocardial perfusion imaging very early after injection of the tracer. We used a very short same-day rest/stress protocol, to be performed within 2 h and evaluated its diagnostic accuracy. The study included 144 patients from seven Spanish and four Portuguese centres with a diagnosis of uncomplicated coronary artery disease (CAD); 78 patients (54%) had no history of prior myocardial infarction. Patients were injected with /=50%) was achieved with a sensitivity of 64% for the left anterior descending artery, 49% for the left circumflex artery and 86% for the right coronary artery, and an accuracy of 71%, 72% and 73% respectively. Concordance of SPET and CA was 62% for single-vessel disease and 68% for multivessel disease. In conclusion, this Spanish-Portuguese multicentre clinical trial confirmed, in a considerable number of patients who underwent coronary angiography, the feasibility of 99mTc tetrofosmin (Myoview) rest/stress myocardial SPET using a very short protocol (2 h).

Effect of anti-TNF and conventional synthetic disease-modifying anti-rheumatic drug treatment on work disability and clinical outcome in a multicentre observational cohort study of psoriatic arthritis.

PubMed

Tillett, William; Shaddick, Gavin; Jobling, Amelia; Askari, Ayman; Cooper, Annie; Creamer, Paul; Clunie, Gavin; Helliwell, Philip S; James, Jana; Kay, Lesley; Korendowych, Eleanor; Lane, Suzanne; Packham, Jonathon; Shaban, Ragai; Thomas, Matthew L; Williamson, Lyn; McHugh, Neil

2017-04-01

To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting. Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure. Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty-two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism ( P = 0.007) and a 15% improvement in work productivity ( P = 0.001) among working patients commenced on csDMARDs ( n = 164) vs a larger and more rapid 30% improvement in presenteeism ( P < 0.001) and 40% improvement in work productivity ( P < 0.001) among those commenced on anti-TNF therapy ( n = 65). Clinical response was poor among patients commenced on a csDMARD ( n = 272), with an 8.4 point improvement in disease activity in PsA ( P < 0.001) vs those commenced on anti-TNF therapy ( n = 121), who had a 36.8 point improvement ( P < 0.001). We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

PubMed

de Vos, L C; Boersema, J; Hillebrands, J L; Schalkwijk, C G; Meerwaldt, R; Breek, J C; Smit, A J; Zeebregts, C J; Lefrandt, J D

2017-04-11

Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY ( A dvanced glycation end-p R oducts in patients with peripheral ar T ery dis E ase and abdominal ao R tic aneur Y sm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. trialregister.nl NTR 5363. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

PubMed

Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-08-01

This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

PubMed Central

Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-01-01

Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925. PMID:24917966

The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study.

PubMed

Katsurada, Naoko; Suzuki, Motoi; Aoshima, Masahiro; Yaegashi, Makito; Ishifuji, Tomoko; Asoh, Norichika; Hamashige, Naohisa; Abe, Masahiko; Ariyoshi, Koya; Morimoto, Konosuke

2017-12-06

Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54-7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but not with chronic respiratory disease. These effects were not affected by age group. The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol

PubMed Central

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-01-01

Introduction The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Methods and analysis Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. Ethics and dissemination This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. Trial registration number NCT01991106. PMID:27044585

Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi-centre Australian study.

PubMed

Tymms, Kathleen; Kelly, Ayano; Bird, Paul; Griffiths, Hedley; de Jager, Julien; Littlejohn, Geoff; Louw, Sandra; Roberts, Lynden; Youssef, Peter; Zochling, Jane; Nichols, Dave

2018-02-01

To describe the treatment regimens, duration of therapy and reasons for disease-modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort. A retrospective non-interventional multi-centre study using Audit4 electronic medical records, with de-identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C-reactive protein [DAS28-CRP]), and reasons for treatment cessation were recorded. A total of 3422 rheumatologist-diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28-CRP results (n = 494), the highest mean DAS28-CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%). Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28-CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Prospective multicentre PCR-based Aspergillus DNA screening in high-risk patients with and without primary antifungal mould prophylaxis.

PubMed

Springer, J; Lackner, M; Nachbaur, D; Girschikofsky, M; Risslegger, B; Mutschlechner, W; Fritz, J; Heinz, W J; Einsele, H; Ullmann, A J; Löffler, J; Lass-Flörl, C

2016-01-01

Invasive aspergillosis (IA) is associated with significant morbidity and mortality, and, among other factors, this is due to a delay in diagnosis performed with conventional techniques. A prospective, multicentre study was conducted to evaluate the efficacy of Aspergillus DNA screening in the early diagnosis of IA. Patients undergoing haematopoietic stem cell transplantation or chemotherapy for acute leukaemia were enrolled for biomarker screening. Three centres applied the same protocol for in-house PCR, which was compliant with the European Aspergillus PCR Initiative recommendations, to guarantee the highest diagnostic standards. Two thousand one hundred and twenty-eight sera from 213 patients were investigated and stratified according to the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria for invasive fungal disease. The incidence rates of probable and possible IA were 18% and 38%, respectively. The sensitivity, specificity and positive predictive value (PPV) of PCR were superior in antifungal drug-naive patients, being 71.4%, 92.3%, and 62.5%, respectively. The last of these key performance indicators (PPV) was moderate in patients receiving primary prophylaxis, at 5.4%. Negative predictive values for both strategies applied were 100% with and 98.3% without antifungal mould prophylaxis. PCR has the potential to play a decisive role in the diagnosis and management of Aspergillus infections in centres not applying primary antifungal mould prophylaxis. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[The discharge form: advantages and limits legionellosis cases individuation].

PubMed

Trerotoli, P; Montagna, M T; Borella, P; Romano Spica, V; Stancanelli, G; Triassi, M; Serio, G; Napoli, C; Soldano, S; Tatò, D; Vercilli, F; Gentile, C; Quaranta, G; Volpe, M; Ambrosio, A; Santarpia, R; Montegrosso, S

2003-01-01

Despite legionellosis surveillance is active in Italy since many years, the disease notification appears still undervalued. A multicentric survey was carried out among 5 big Italian hospitals. It examined 11,435 discharge forms (1999-2001), reporting pneumonia diagnosis. Legionellosis (II class of notify system for infectious disease) was studied among pneumonia diagnosis by discharge forms. According to the ICD9-CM, there's no specific code for legionellosis (this disease is included among "others gram-negative pneumonia"). So the presumed pneumonia imputable to Legionella spp were the 2.7% of the whole number of analyzed discharge forms. Besides, the data regarding the other pneumonia showed that the etiological agent was specified only in the 11.2% of the case. This situation could be rectified both introducing adequate discharge forms codes and promoting the etiological diagnosis during the hospital stay.

Conducting a paediatric multi-centre RCT with an industry partner: challenges and lessons learned.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2012-11-01

There are many benefits of multi-centred research including large sample sizes, statistical power, timely recruitment and generalisability of results. However, there are numerous considerations when planning and implementing a multi-centred study. This article reviews the challenges and successes of planning and implementing a multi-centred prospective randomised control trial involving an industry partner. The research investigated the impact on psychosocial functioning of a cosmetic camouflage product for children and adolescents with burn scarring. Multi-centred studies commonly have many stakeholders. Within this study, six Australian and New Zealand paediatric burn units as well as an industry partner were involved. The inclusion of an industry partner added complexities as they brought different priorities and expectations to the research. Further, multifaceted ethical and institutional approval processes needed to be negotiated. The challenges, successes, lessons learned and recommendations from this study regarding Australian and New Zealand ethics and research governance approval processes, collaboration with industry partners and the management of differing expectations will be outlined. Recommendations for future multi-centred research with industry partners include provision of regular written reports for the industry partner; continual monitoring and prompt resolution of concerns; basic research practices education for industry partners; minimisation of industry partner contact with participants; clear roles and responsibilities of all stakeholders and utilisation of single ethical review if available. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

PubMed

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials.

Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases.

PubMed

Moreno, C; Cuesta-Herranz, J; Fernández-Távora, L; Alvarez-Cuesta, E

2004-04-01

The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17,526 administered doses, 17,368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The natural history of HIV infection in intravenous drug users: risk of disease progression in a cohort of seroconverters.

PubMed

Rezza, G; Lazzarin, A; Angarano, G; Sinicco, A; Pristerà, R; Ortona, L; Barbanera, M; Gafà, S; Tirelli, U; Salassa, B

1989-02-01

A multicentre cohort study was carried out to estimate the incidence of AIDS and HIV-related conditions in newly infected intravenous drug users (IVDU). The enrollment criteria included the identification of the seroconversion time. Two hundred and five subjects entered the study, and were followed for a mean of 26 months. Twelve subjects developed clinical AIDS over a 4-year period. The actuarial incidence of AIDS estimated by Kaplan-Meier survival technique was 17.8% by 4 years since seroconversion. The risk of developing AIDS increased significantly after 24 months from seroconversion. Relatively small figures accounted for the lack of statistical association between the risk factors investigated and the disease status.

Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.

PubMed

Nyangoh Timoh, Krystel; Stewart, Zelda; Benjoar, Mikhael; Beldjord, Selma; Ballester, Marcos; Bazot, Marc; Thomassin-Naggara, Isabelle; Darai, Emile

To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis. A prospective study (Canadian Task Force classification II-2). Tenon University Hospital, Paris, France. Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included. Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections. The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61). MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosis than conventional MRI. Copyright © 2018. Published by Elsevier Inc.

Multi-Centrality Graph Spectral Decompositions and Their Application to Cyber Intrusion Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Pin-Yu; Choudhury, Sutanay; Hero, Alfred

Many modern datasets can be represented as graphs and hence spectral decompositions such as graph principal component analysis (PCA) can be useful. Distinct from previous graph decomposition approaches based on subspace projection of a single topological feature, e.g., the centered graph adjacency matrix (graph Laplacian), we propose spectral decomposition approaches to graph PCA and graph dictionary learning that integrate multiple features, including graph walk statistics, centrality measures and graph distances to reference nodes. In this paper we propose a new PCA method for single graph analysis, called multi-centrality graph PCA (MC-GPCA), and a new dictionary learning method for ensembles ofmore » graphs, called multi-centrality graph dictionary learning (MC-GDL), both based on spectral decomposition of multi-centrality matrices. As an application to cyber intrusion detection, MC-GPCA can be an effective indicator of anomalous connectivity pattern and MC-GDL can provide discriminative basis for attack classification.« less

IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care.

PubMed

Clarkson, Jan E; Ramsay, Craig R; Averley, Paul; Bonetti, Debbie; Boyers, Dwayne; Campbell, Louise; Chadwick, Graham R; Duncan, Anne; Elders, Andrew; Gouick, Jill; Hall, Andrew F; Heasman, Lynne; Heasman, Peter A; Hodge, Penny J; Jones, Clare; Laird, Marilyn; Lamont, Thomas J; Lovelock, Laura A; Madden, Isobel; McCombes, Wendy; McCracken, Giles I; McDonald, Alison M; McPherson, Gladys; Macpherson, Lorna E; Mitchell, Fiona E; Norrie, John Dt; Pitts, Nigel B; van der Pol, Marjon; Ricketts, David Nj; Ross, Margaret K; Steele, James G; Swan, Moira; Tickle, Martin; Watt, Pauline D; Worthington, Helen V; Young, Linda

2013-10-26

Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care. This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0-3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI.Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases.The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the gingival margin; oral hygiene self-efficacy and net benefits. IQuaD will provide evidence for the most clinically-effective and cost-effective approach to managing periodontal disease in dentate adults in Primary Care. This will support general dental practitioners and patients in treatment decision making. Protocol ID: ISRCTN56465715.

IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

PubMed Central

2013-01-01

Background Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care. Methods/Design This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0–3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI. Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases. The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the gingival margin; oral hygiene self-efficacy and net benefits. Discussion IQuaD will provide evidence for the most clinically-effective and cost-effective approach to managing periodontal disease in dentate adults in Primary Care. This will support general dental practitioners and patients in treatment decision making. Trial registration Protocol ID: ISRCTN56465715 PMID:24160246

[Pearson syndrome. Case report].

PubMed

Cammarata-Scalisi, Francisco; López-Gallardo, Ester; Emperador, Sonia; Ruiz-Pesini, Eduardo; Da Silva, Gloria; Camacho, Nolis; Montoya, Julio

2011-09-01

Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are infrequent. Pearson syndrome is diagnosed principally during the initial stages of life and it is characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and variable neurologic, hepatic, renal and endocrine failures. We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. This entity has been associated to diverse phenotypes within the broad clinical spectrum of mitochondrial disease.

Socioeconomic Factors and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography: A Multicentre Study of Arabian Gulf States.

PubMed

Daoulah, Amin; Elkhateeb, Osama E; Nasseri, S Ali; Al-Murayeh, Mushabab; Al-Kaabi, Salem; Lotfi, Amir; Alama, Mohamed N; Al-Faifi, Salem M; Haddara, Mamdouh; Dixon, Ciaran M; Alzahrani, Ibrahim S; Alghamdi, Abdullah A; Ahmed, Waleed; Fathey, Adnan; Haq, Ejazul; Alsheikh-Ali, Alawi A

2017-01-01

Coronary artery disease (CAD) is a leading cause of death worldwide. The association of socioeconomic status with CAD is supported by numerous epidemiological studies. Whether such factors also impact the number of diseased coronary vessels and its severity is not well established. We conducted a prospective multicentre, multi-ethnic, cross sectional observational study of consecutive patients undergoing coronary angiography (CAG) at 5 hospitals in the Kingdom of Saudi Arabia and the United Arab Emirates. Baseline demographics, socioeconomic, and clinical variables were collected for all patients. Significant CAD was defined as ≥70% luminal stenosis in a major epicardial vessel. Left main disease (LMD) was defined as ≥50% stenosis in the left main coronary artery. Multi-vessel disease (MVD) was defined as having >1 significant CAD. Of 1,068 patients (age 59 ± 13, female 28%, diabetes 56%, hypertension 60%, history of CAD 43%), 792 (74%) were from urban and remainder (26%) from rural communities. Patients from rural centres were older (61 ± 12 vs 58 ± 13), and more likely to have a history of diabetes (63 vs 54%), hypertension (74 vs 55%), dyslipidaemia (78 vs 59%), CAD (50 vs 41%) and percutaneous coronary intervention (PCI) (27 vs 21%). The two groups differed significantly in terms of income level, employment status and indication for angiography. After adjusting for baseline differences, patients living in a rural area were more likely to have significant CAD (adjusted OR 2.40 [1.47, 3.97]), MVD (adjusted OR 1.76 [1.18, 2.63]) and LMD (adjusted OR 1.71 [1.04, 2.82]). Higher income was also associated with a higher risk for significant CAD (adjusted OR 6.97 [2.30, 21.09]) and MVD (adjusted OR 2.49 [1.11, 5.56]), while unemployment was associated with a higher risk of significant CAD (adjusted OR 2.21, [1.27, 3.85]). Communal and socioeconomic factors are associated with higher odds of significant CAD and MVD in the group of patients referred for CAG. The underpinnings of these associations ( e.g. pathophysiologic factors, access to care, and system-wide determinants of quality) require further study.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.

PubMed

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-10-09

This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. EUDRACT Reference Number: 2012-002764-27. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials

PubMed Central

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

Purpose This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. PMID:27467882

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

PubMed

Bisceglia, M; Spagnolo, D; Galliani, C; Fisher, C; Suster, S; Kazakov, D V; Cooper, K; Michal, M

2006-08-01

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Specificity of the histopathological triad for the diagnosis of toxoplasmic lymphadenitis: polymerase chain reaction study.

PubMed

Lin, M H; Kuo, T T

2001-08-01

Toxoplasmosis is a common cause of lymphadenopathy, but toxoplasmic cysts are not usually found in histological sections used for establishing diagnosis, except on extremely rare occasions. The histopathological triad of florid reactive follicular hyperplasia, clusters of epithelioid histiocytes, and focal sinusoidal distention by monocytoid B cells has been considered to be diagnostic of toxoplasmic lymphadenitis, but the validity of the histopathological triad is based indirectly on serological correlation only. The demonstration of Toxoplasma gondii DNA in lymph nodes displaying the histopathological triad will indicate the validity of the histopathological triad as the criterion for the histopathological diagnosis of toxoplasmic lymphadenitis. We used frozen tissues of 12 lymph nodes with the histopathological triad and tissues of 27 lymph nodes from patients with various other conditions (including 13 cases of follicular lymphoid hyperplasia, FLH; three cases of dermatopathic lymphadenopathy, DPL; two cases of plasmacytosis; two cases of Castleman's disease; two cases of metastatic adenocarcinoma; and five cases of lymphoma) to detect T. gondii DNA by polymerase chain reaction. Ten out of 12 lymph nodes with the triad and six out of 27 lymph nodes without the triad were positive for T. gondii DNA. Thus, the sensitivity of the triad was 62.5% (10/16) and the specificity was 91.3% (21/23). The predictive value of positive tests was 83.3% (10/12) and the predictive value of negative tests was 77.7% (21/27). The six cases positive for T. gondii DNA without the triad were four cases of FLH, one case of DPL, and one case of plasmacytosis. None of the neoplastic diseases was positive. The false positive and negative cases could be due to sampling problems or past T. gondii infection. The results confirm that the histopathological triad is highly specific for the diagnosis of toxoplasmic lymphadenitis and can be used confidently.

The importance of international collaboration for rare diseases research: a European perspective

PubMed Central

Julkowska, D; Austin, C P; Cutillo, C M; Gancberg, D; Hager, C; Halftermeyer, J; Jonker, A H; Lau, L P L; Norstedt, I; Rath, A; Schuster, R; Simelyte, E; van Weely, S

2017-01-01

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease. PMID:28440796

The importance of international collaboration for rare diseases research: a European perspective.

PubMed

Julkowska, D; Austin, C P; Cutillo, C M; Gancberg, D; Hager, C; Halftermeyer, J; Jonker, A H; Lau, L P L; Norstedt, I; Rath, A; Schuster, R; Simelyte, E; van Weely, S

2017-09-01

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.

Outcomes after resection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Kinoshita, Masahiko; Hamano, Genya; Ito, Tokuji; Koda, Masaki; Aota, Takanori; Yamamoto, Takatsugu; Terajima, Hiroaki; Tachiyama, Gorou; Yamada, Terumasa; Nakamori, Shoji; Arimoto, Akira; Fujikawa, Masahiro; Tomimaru, Yoshito; Sugawara, Yasuhiko; Nakagawa, Kei; Unno, Michiaki; Mizuguchi, Toru; Takenaka, Kenji; Kimura, Koichi; Shirabe, Ken; Saiura, Akio; Uesaka, Katsuhiko; Taniguchi, Hiroki; Fukuda, Akira; Chong, Ja-Mun; Kuwae, Yuko; Ohsawa, Masahiko; Sato, Yasunori; Nakanuma, Yasuni

2016-09-01

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Authorship issues in multi-centre clinical trials: the importance of making an authorship contract.

PubMed

Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian; Vinther, Siri

2015-02-01

Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them to qualify for authorship as defined by the International Committee of Medical Journal Editors. Therefore, rules for authorship in multi-centre trials are strongly recommended. We propose two contracts to prevent conflicts regarding authorship; both are freely available for use without pay but with reference to the original source.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

PubMed

Miller, Julie M; Dewey, Marc; Vavere, Andrea L; Rochitte, Carlos E; Niinuma, Hiroyuki; Arbab-Zadeh, Armin; Paul, Narinder; Hoe, John; de Roos, Albert; Yoshioka, Kunihiro; Lemos, Pedro A; Bush, David E; Lardo, Albert C; Texter, John; Brinker, Jeffery; Cox, Christopher; Clouse, Melvin E; Lima, João A C

2009-04-01

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

PubMed

Gathani, Toral; Barnes, Isobel; Ali, Raghib; Arumugham, Rajkumar; Chacko, Raju; Digumarti, Raghunadharao; Jivarajani, Parimal; Kannan, Ravi; Loknatha, Dasappa; Malhotra, Hemant; Mathew, Beela S

2017-01-18

The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma.

PubMed

van der Steen-Banasik, E; Christiaens, M; Shash, E; Coens, C; Casado, A; Herrera, F G; Ottevanger, P B

2016-09-01

Radiotherapy is a good option for inoperable and frail patients diagnosed with endometrial cancer. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of this specific approach. We performed a bibliographic search for articles in English or French which were published in PubMed from the start of this database in January 1969 to identify publications on radiation therapy (RT) as single treatment for localised non-operable carcinoma of the endometrium. The review was completed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Twenty-five reports containing 2694 patients treated with RT as single treatment were identified that fulfilled the selection criteria. Disease-specific survival (DSS) at 5 years was reported for a cohort of 1322 (49.1%) patients. The combined DSS for this group of patients was 78.5% (range: 68.4-92%; 95% confidence interval: 74.5-82.5). External beam radiation therapy (EBRT) combined with brachytherapy (BT) was used in 1278 patients (47.4%), BT alone in 1383 patients (51.3%), and EBRT alone in 33 patients (1.2%). The average occurrence of grade III or worse late toxicity was 3.7% for EBRT + BT, 2.8% for BT alone, and 1.2% for EBRT alone. RT is in terms of disease control and toxicity, an acceptable option for non-surgical candidate patients. Prospective multicentre randomised or observational trials are needed to validate these results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Results of a prospective multicentre myeloablative double-unit cord blood transplantation trial in adult patients with acute leukaemia and myelodysplasia.

PubMed

Barker, Juliet N; Fei, Mingwei; Karanes, Chatchada; Horwitz, Mitchell; Devine, Steven; Kindwall-Keller, Tamila L; Holter, Jennifer; Adams, Alexia; Logan, Brent; Navarro, Willis H; Riches, Marcie

2015-02-01

Double-unit cord blood (CB) grafts may improve engraftment and relapse risk in adults with haematological malignancies. We performed a prospective high-dose myeloablative double-unit CB transplantation (CBT) trial in adults with high-risk acute leukaemia or myelodysplasia (MDS) between 2007 and 2011. The primary aim was to establish the 1-year overall survival in a multi-centre setting. Fifty-six patients (31 acute myeloid leukaemia, 19 acute lymphoblastic leukaemia, 4 other acute leukaemias, 2 myelodysplastic syndrome [MDS]) were transplanted at 10 centres. The median infused total nucleated cell doses were 2·62 (larger unit) and 2·02 (smaller unit) x 10(7) /kg. The cumulative incidence of day 100 neutrophil engraftment was 89% (95% confidence interval [CI]: 80-96). Day 180 grade II-IV acute graft-versus-host disease (GVHD) incidence was 64% (95%CI: 51-76) and 36% (95%CI: 24-49) of patients had chronic GVHD by 3-years. At 3-years post-transplant, the transplant-related mortality (TRM) was 39% (95%CI: 26-52), and the 3-year relapse incidence was 11% (95%CI: 4-21). With a median 37-month (range 23-71) follow-up of survivors, the 3-year disease-free survival was 50% (95%CI: 37-63). Double-unit CBT is a viable alternative therapy for high-risk acute leukaemia/ MDS in patients lacking a matched unrelated donor. This is especially important for minority patients. The relapse incidence was low but strategies to ameliorate TRM are needed. © 2014 John Wiley & Sons Ltd.

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial.

PubMed

Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

2016-03-02

Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications. NCT02040441; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma.

PubMed

Daters, A T; Mauldin, G E; Mauldin, G N; Brodsky, E M; Post, G S

2010-03-01

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

PubMed Central

Cooney, Rachel M; Warren, Bryan F; Altman, Douglas G; Abreu, Maria T; Travis, Simon PL

2007-01-01

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached. PMID:17592647

Type 1 diabetes: New horizons in prediction and prevention.

PubMed

Razack, Natasha N; Wherrett, Diane K

2005-01-01

Significant advances have been made in our understanding of the pathogenesis of type 1 diabetes and our ability to predict risk for the condition. This knowledge is being used to develop new and innovative strategies to prevent type 1 diabetes or to prevent further destruction of beta cells in those who are newly diagnosed. Several multicentre studies are underway investigating the natural history of the disease, the genetics behind the disease and ways to stop the autoimmune reaction against beta cells (Type 1 Diabetes TrialNet, Type 1 Diabetes Genetics Consortium and the Trial to Reduce Diabetes in the Genetically at Risk [TRIGR] Study Group). The stage is set to find an agent or strategy to prevent type 1 diabetes or to preserve the residual beta cell mass in new-onset patients.

Multi-centric universal pseudonymisation for secondary use of the EHR.

PubMed

Lo Iacono, Luigi

2007-01-01

This paper discusses the importance of protecting the privacy of patient data kept in an Electronic Health Record (EHR) in the case, where it leaves the control- and protection-sphere of the health care realm for secondary uses such as clinical or epidemiological research projects, health care research, assessment of treatment quality or economic assessments. The paper focuses on multi-centric studies, where various data sources are linked together using Grid technologies. It introduces a pseudonymisation system which enables a multi-centric universal pseudonymisation, meaning that a patient's identity will result in the same pseudonym, regardless of which participating study center the patient data is collected.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

PubMed

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure. © 2013 British Association of Dermatologists.

Predictors of treatment success after Collagenase clostridium histolyticum injection for Peyronie's disease. Development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study.

PubMed

Cocci, Andrea; Russo, Giorgio Ivan; Briganti, Alberto; Salonia, Andrea; Cacciamani, Giovanni; Capece, Marco; Falcone, Marco; Timpano, Massimiliano; Cito, Gianmartin; Verze, Paolo; Giammusso, Bruno; Morgia, Giuseppe; Mirone, Vincenzo; Minervini, Andrea; Gacci, Mauro; Cai, Tommaso; Serni, Sergio; Carini, Marco; Giubilei, Gianluca; Mondaini, Nicola

2018-05-23

To build-up a nomogram able to predict treatment success after Collagenase clostridium histolyticum (CCH) for Peyronie's disease (PD). From November 2016 to November 2017, we enrolled 135 patients with PD in a multicentre single-arm prospective study. All patients enrolled had a treatment with CCH. Success of therapy was defined as a penile curvature decrease of at least 20 degrees from baseline curvature. Treatment satisfaction was assessed using a scale from 1 to 10 and high satisfaction was arbitral defined as a score ≥8. The calcification level was classified as: absence of calcifications, low spots perilesional calcifications and high calcification. Median age was 56.0 (IQR [interquartile range]: 45.0,65.0) and median penile curvature (PC) was 30 degrees (IQR: 30.0,60.0). After the treatment protocol, we observed a significant median change for PC of -20.0 (p<0.01). The median percentage of penile curvature improvement was 44 (IQR: 28.0-67.0). Overall median satisfaction was 8.0 (IQR: 7.0-9.0). In total, treatment efficacy was reported in 77 patients (57.04%). When analysing factors associated with PC improvement after treatment, we found that baseline PC (OR= 1.14; p<0.01), basal plaque (OR= 64.27; p<0.01), low calcification (OR= 0.06; p<0.01) and high-calcification (OR= 0.03; p<0.01) were significant predictors of penile curvature improvement. The c-index for the model was 0.93. Patients with longer duration of the disease, greater baseline curvature and basal plaque localization were at greater chance of treatment success. These results could be applied into clinical practice before external validation of our nomogram. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol.

PubMed

Rouch, Isabelle; Dorey, Jean-Michel; Boublay, Nawèle; Henaff, Marie-Anne; Dibie-Racoupeau, Florence; Makaroff, Zaza; Harston, Sandrine; Benoit, Michel; Barrellon, Marie-Odile; Fédérico, Denis; Laurent, Bernard; Padovan, Catherine; Krolak-Salmon, Pierre

2014-10-10

Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms. Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months. This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers. ClincalTrials.gov: NCT01297140.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

PubMed

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-04-04

The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. NCT01991106. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III-rationale, trial design and baseline data.

PubMed

2017-12-01

Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

PubMed Central

Judge, PK; Haynes, R; Herrington, WG; Storey, BC; Staplin, N; Bethel, A; Bowman, L; Brunskill, N; Cockwell, P; Dayanandan, R; Hill, M; Kalra, PA; McMurray, JJ; Taal, M; Wheeler, DC; Landray, MJ; Baigent, C; Baigent, C; Haynes, R; Landray, MJ; Dayanandan, R; Baxter, A; Staplin, N; Bethel, A; Bowman, L; Brunskill, N; Cockwell, P; Herrington, WG; Hill, M; Judge, PK; Kalra, PA; Knott, C; McMurray, JJ; Murphy, K; Taal, M; Wheeler, DC; Wheatley, K; Emberson, J; Tomson, C; Roderick, P

2017-01-01

Abstract Background Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. Methods UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor–neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin–angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Results Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. Conclusions UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD. PMID:27646835

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

PubMed Central

Rolland, Yan; Vérin, Marc; Payan, Christine A; Duchesne, Simon; Kraft, Eduard; Hauser, Till K; Jarosz, Josef; Deasy, Neil; Defevbre, Luc; Delmaire, Christine; Dormont, Didier; Ludolph, Albert C; Bensimon, Gilbert

2011-01-01

Aim To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. Methods The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP=362, MSA=398), 627 had per protocol images (PSP=297, MSA=330). Intra-rater (n=60) and inter-rater (n=555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n=441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. Results Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75–0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1–F2; MSA: F2–F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. Conclusions The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224. PMID:21386111

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Early Lupus Project - A multicentre Italian study on systemic lupus erythematosus of recent onset.

PubMed

Sebastiani, G D; Prevete, I; Piga, M; Iuliano, A; Bettio, S; Bortoluzzi, A; Coladonato, L; Tani, C; Spinelli, F R; Fineschi, I; Mathieu, A

2015-10-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset that is problematic for a correct and prompt diagnosis. We undertook this project with the purpose of collecting an inception cohort of Italian patients with recent-onset SLE, in order to obtain information on the main clinical and serological characteristics at the beginning of the disease. In this first report we describe the characteristics of this cohort at study entry. All patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled between 1 January 2012 and 31 December 2013 in a multicentre prospective study. Information on clinical and serological characteristics at study entry and then every six months was collected into a specific electronic database. Statistical analysis was performed by means of the Openstat program. Among 122 patients enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9) months. The frequency of the manifestations included in the 1997 ACR criteria was as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm, antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders 55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders 27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%. The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment, autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%, anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant 16.3%, anti-Sm 16%, and anti-SSB 13.1%. In this paper we describe the main clinical and serological characteristics of an Italian inception cohort of patients with recent-onset SLE. At disease onset, mucocutaneous manifestations, arthritis and haematologic manifestations were the most frequent symptoms; ANA, anti-dsDNA and complement reduction were the most frequent laboratory findings. Our data confirm that the diagnosis of SLE is a challenging one, and that SLE is a severe disease even at onset, since the majority of patients require at least a hospitalization before the diagnosis. © The Author(s) 2015.

Traumatic injury to the colon and rectum in Scotland: demographics and outcome.

PubMed

Brady, R R; O'Neill, S; Berry, O; Kerssens, J J; Yalamarthi, S; Parks, R W

2012-01-01

An analysis of a multi-centred database of trauma patients was performed. The study used data from a prospective multi-centre trauma database containing details of 52 887 trauma patients admitted to participating Scottish Hospitals over an 11-year period. Three hundred and forty (0.64%) of 52 887 trauma patients (284 male) with colorectal injuries were identified; 43.9% of colorectal injuries occurred following blunt trauma and 56.1% following penetrating injury. Patients in the latter group were younger, had less haemodynamic compromise and were less likely to die than those with blunt trauma (P < 0.01). The overall mortality rate was 25.6% and after rectal injury it was 21.2% (P > 0.05). Female gender, increased age, road traffic accidents and those admitted as a result of a blunt traumatic injury were associated with increased mortality. Age > 65 years (P = 0.01), increasing injury severity score (ISS) at presentation (P < 0.001), haemodynamic compromise (P = 0.045) and decreased Glasgow Coma Score (GCS) (P < 0.001) had the strongest independent associations with mortality. Colorectal injury after trauma has a high morbidity. Clinical features associated with death allow stratification of mortality risk. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

HPV and cofactors for invasive cervical cancer in Morocco: a multicentre case-control study.

PubMed

Berraho, Mohamed; Amarti-Riffi, Afaf; El-Mzibri, Mohammed; Bezad, Rachid; Benjaafar, Noureddine; Benideer, Abdelatif; Matar, Noureddine; Qmichou, Zinab; Abda, Naima; Attaleb, Mohammed; Znati, Kaoutar; El Fatemi, Hind; Bendahhou, Karima; Obtel, Majdouline; Filali Adib, Abdelhai; Mathoulin-Pelissier, Simone; Nejjari, Chakib

2017-06-20

Limited national information is available in Morocco on the prevalence and distribution of HPV-sub-types of cervical cancer and the role of other risk factors. The aim was to determine the frequency of HPV-sub-types of cervical cancer in Morocco and investigate risk factors for this disease. Between November 2009 and April 2012 a multicentre case-control study was carried out. A total of 144 cases of cervical cancer and 288 age-matched controls were included. Odds-ratios and corresponding confidence-intervals were computed by conditional logistic regression models. Current HPV infection was detected in 92.5% of cases and 13.9% of controls. HPV16 was the most common type for both cases and controls. Very strong associations between HPV-sub-types and cervical cancer were observed: total-HPV (OR = 39), HPV16 (OR = 49), HPV18 (OR = 31), and multiple infections (OR = 13). Education, high parity, sexual intercourse during menstruation, history of sexually transmitted infections, and husband's multiple sexual partners were also significantly associated with cervical cancer in the multivariate analysis. Our results could be used to establish a primary prevention program and to prioritize limited screening to women who have specific characteristics that may put them at an increased risk of cervical cancer.

Low incidence but poor prognosis of complicated coeliac disease: a retrospective multicentre study.

PubMed

Biagi, Federico; Gobbi, Paolo; Marchese, Alessandra; Borsotti, Edoardo; Zingone, Fabiana; Ciacci, Carolina; Volta, Umberto; Caio, Giacomo; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Corazza, Gino R

2014-03-01

Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Multicentric GISCoR Study "intensive clinical follow-up versus surgical radicalization after complete endoscopic polypectomy of a malignant adenoma" (SEC-GISCoR).

PubMed

Andreoni, Bruno; Camellini, Lorenzo; Sonzogni, Angelica; Crosta, Cristiano; Pirola, Maria Elena; Corbellini, Carlo

2011-09-01

Colorectal cancer screening programs result in an early diagnosis of the disease. In 2007, 250 malignant polyps were identified in Lombardy, out of 1,329 screen-detected colorectal carcinomas. The Italian Group for Colorectal Cancer (GISCoR) promoted the multicentric study "Endoscopic Follow-up versus Surgical Radicalization of Malignant Polyps after Complete Endoscopic Polypectomy" (SEC-GISCoR). The protocol was a multicentric, prospective, observational, non-randomized study. It included patients diagnosed a colorectal malignant adenoma, after complete endoscopic removal. From November 2005 to September 2009, three participating centers enrolled 120 patients with malignant polyps after "complete" endoscopic polypectomy; malignant polyps were classified as "low risk" or "high risk". The study had two arms: "Intensive follow-up" (42 patients: 32 with low-risk and 10 with high-risk polyps) and "Surgical radicalization" (78 patients: 5 with low-risk and 73 with high-risk polyps). Data were collected using an online CRF. Overall, 37/120 polyps (30.8%) were low risk and 83/120 (69.2%) were high risk. 42 out of 120 patients (35%) were enrolled in the "clinical follow-up" arm, while 78/120 (65%) entered the surgery arm. In 15 cases, patients were not enrolled in the correct arm, according to the criteria agreed upon before starting the study. There still is a high incidence (11.5%) of pathological mismatches. No clinical event was reported in 2.9 years of follow-up. In conclusion, some differences emerged in the management of patients with malignant polyps among participating centers (p < 0.001), mismatches can be explained by high surgical risk or patient's choice. Only in 5 cases (4.2%), did data analysis not allow to exactly determine the reason for a choice different from protocol criteria. The availability of new risk factors and the evidence of pathological mismatches confirmed the need for future studies on this issue.

Intrahepatic Cholangiocarcinoma: expert consensus statement

PubMed Central

Weber, Sharon M; Ribero, Dario; O=Reilly, Eileen M; Kokudo, Norihiro; Miyazaki, Masaru; Pawlik, Timothy M

2015-01-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions. PMID:26172134

High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

PubMed

van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

2017-12-01

Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial.

PubMed

Napp, Adriane E; Haase, Robert; Laule, Michael; Schuetz, Georg M; Rief, Matthias; Dreger, Henryk; Feuchtner, Gudrun; Friedrich, Guy; Špaček, Miloslav; Suchánek, Vojtěch; Fuglsang Kofoed, Klaus; Engstroem, Thomas; Schroeder, Stephen; Drosch, Tanja; Gutberlet, Matthias; Woinke, Michael; Maurovich-Horvat, Pál; Merkely, Béla; Donnelly, Patrick; Ball, Peter; Dodd, Jonathan D; Quinn, Martin; Saba, Luca; Porcu, Maurizio; Francone, Marco; Mancone, Massimo; Erglis, Andrejs; Zvaigzne, Ligita; Jankauskas, Antanas; Sakalyte, Gintare; Harań, Tomasz; Ilnicka-Suckiel, Malgorzata; Bettencourt, Nuno; Gama-Ribeiro, Vasco; Condrea, Sebastian; Benedek, Imre; Čemerlić Adjić, Nada; Adjić, Oto; Rodriguez-Palomares, José; Garcia Del Blanco, Bruno; Roditi, Giles; Berry, Colin; Davis, Gershan; Thwaite, Erica; Knuuti, Juhani; Pietilä, Mikko; Kępka, Cezary; Kruk, Mariusz; Vidakovic, Radosav; Neskovic, Aleksandar N; Díez, Ignacio; Lecumberri, Iñigo; Geleijns, Jacob; Kubiak, Christine; Strenge-Hesse, Anke; Do, The-Hoang; Frömel, Felix; Gutiérrez-Ibarluzea, Iñaki; Benguria-Arrate, Gaizka; Keiding, Hans; Katzer, Christoph; Müller-Nordhorn, Jacqueline; Rieckmann, Nina; Walther, Mario; Schlattmann, Peter; Dewey, Marc

2017-07-01

More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

Temporal trends in critical events complicating HIV infection: 1999-2010 multicentre cohort study in France.

PubMed

Barbier, François; Roux, Antoine; Canet, Emmanuel; Martel-Samb, Patricia; Aegerter, Philippe; Wolff, Michel; Guidet, Bertrand; Azoulay, Elie

2014-12-01

Multicentre data are limited to appraise the management and prognosis of critically ill human immunodeficiency virus (HIV)-infected patients. We sought to describe temporal trends in demographic and clinical characteristics, indications for intensive care and outcome in this patient population. We conducted a cohort study of unselected HIV-infected patients admitted between 1999 and 2010 to 34 French ICUs contributing to the CUB-Réa prospective database. We included 6,373 consecutive patients. Over the 12-year period, increases occurred in median age (39 years in 1999-2001; 47 years in 2008-2010, p < 0.0001) and prevalence of comorbidities (notably malignancies, from 6.7 to 16.4%, p < 0.0001). Admissions for respiratory failure (39.8% overall), shock (8.1%) and coma (22.7%) decreased (p < 0.0001), while those for sepsis (19.3%) remained stable. The main final diagnoses were bacterial sepsis (24.6%) and non-bacterial acquired immune deficiency syndrome (AIDS)-defining diseases (steady decline from 26.0 to 17.5%, p < 0.0001). Patients increasingly received mechanical ventilation (from 42.9 to 54.0%) and renal replacement therapy (from 9.6 to 16.8%) (p < 0.0001), whereas vasopressor use remained stable (27.4%). ICU readmissions increased after 2004 (p < 0.0001). ICU and hospital mortality (17.6 and 26.9%, respectively) dropped markedly in the most severely ill patients requiring multiple life-sustaining therapies. Malignancies and chronic liver disease were heavily associated with hospital mortality by multivariate analysis, while the most common AIDS-defining complications (Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis and tuberculosis) had no independent impact. Progressive ageing, increasing prevalence of comorbidities (mainly malignancies), a steady decline in AIDS-related illnesses and improved benefits from life-sustaining therapies were the main temporal trends in HIV-infected patients requiring ICU admission.

The German ROP Registry: data from 90 infants treated for retinopathy of prematurity.

PubMed

Walz, Johanna M; Bemme, Sebastian; Pielen, Amelie; Aisenbrey, Sabine; Breuß, Helge; Alex, Anne F; Wagenfeld, Lars; Schiedel, Susanne; Krohne, Tim U; Stahl, Andreas

2016-12-01

The German retinopathy of prematurity (ROP) Registry collects data on treated ROP in a multicentre approach to analyse epidemiology and treatment patterns of severe ROP. Nine centres entered data from 90 treated ROP infants (born between January 2011 and December 2013) into a central database. Analysis included incidence rate of severe ROP, demographic data, stage of ROP, treatment patterns, recurrence rates, relevant comorbidities and ophthalmological or systemic complications associated with treatment. Treatment rate for ROP was 3.2% of the screened population. The most frequent ROP stage at time of treatment was zone II, stage 3 +  (137 eyes). Treatment was bilateral in 97% of infants. Treatment patterns changed over time from 7% anti-vascular endothelial growth factor (VEGF) monotherapy in 2011 to 32% in 2014. Overall, laser treatment was the predominant treatment. However, all infants with zone I disease received anti-VEGF treatment. About 19% of infants required retreatment (16% of laser-treated and 21% of anti-VEGF treated infants). Mean time between first and second treatment was 3.8 weeks (± 11 days) for laser-treated and 10.4 weeks (± 60 days) for anti-VEGF-treated infants. This study is the first multicentre analysis of severe ROP in Germany. The identified treatment patterns find laser as the most prevalent form of therapy, with an increasing use of anti-VEGF therapy over recent years. Recurrence rates were relatively high overall with slightly higher recurrence rates and later recurrence times in the anti-VEGF group. Anti-VEGF was predominantly used for high-risk stages like AP-ROP and zone I disease. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study.

PubMed

Hoogendoorn, Robert J; Groeneveld, Lex; Kwee, J Andy

2009-01-01

To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole. This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed. Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred. Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

PubMed

Atienza-Mateo, Belén; Calvo-Río, Vanesa; Beltrán, Emma; Martínez-Costa, Lucía; Valls-Pascual, Elia; Hernández-Garfella, Marisa; Atanes, Antonio; Cordero-Coma, Miguel; Miquel Nolla, Joan; Carrasco-Cubero, Carmen; Loricera, Javier; González-Vela, María C; Vegas-Revenga, Nuria; Fernández-Díaz, Carlos; Demetrio-Pablo, Rosalía; Domínguez-Casas, Lucía C; Luis Martín-Varillas, José; Palmou-Fontana, Natalia; Hernández, José L; González-Gay, Miguel Á; Blanco, Ricardo

2018-05-01

To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.

PubMed

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, James; Sharma, Padmanee; Eng, Cathy

2017-04-01

Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study

PubMed Central

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Prof Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, Prof James; Sharma, Prof Padmanee; Eng, Prof Cathy

2018-01-01

Summary Background Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. Methods We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. Findings We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. Interpretation To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. Funding National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. PMID:28223062

[Generalized eruptive histiocytoma. Apropos of a case. Review of the literature].

PubMed

Bobin, P; Carsuzaa, F; Seurat, P; Lucas, D

1983-01-01

About one case of generalized eruptive histiocytoma (G.E.H.) (the second French case) and about thirteen others cases mentioned in literature, the authors remind the clinical, histological, immuno-histochemical and evolutive aspects of this misunderstanding disease, described by Winkelmann in 1963. After having classed it, in the group of nodular, non X, non lipidique, benign histiocytosis, they expose the imprecision of this nosological limits of the G.E.H., in comparison to the bordering diseases. At last, they insist upon the fact that the few number of cases published up to this time, the lack of stand back and the casual transformation into a multicentric reticulo-histiocytosis must induce to watchfulness by requiring for each patient affected by G. E. H. and for a long time, a regular, clinical, radiological and hematological supervision.

Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy.

PubMed

Parini, Rossella; De Lorenzo, Paola; Dardis, Andrea; Burlina, Alberto; Cassio, Alessandra; Cavarzere, Paolo; Concolino, Daniela; Della Casa, Roberto; Deodato, Federica; Donati, Maria Alice; Fiumara, Agata; Gasperini, Serena; Menni, Francesca; Pagliardini, Veronica; Sacchini, Michele; Spada, Marco; Taurisano, Roberta; Valsecchi, Maria Grazia; Di Rocco, Maja; Bembi, Bruno

2018-02-08

Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

Socioeconomic Factors and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography: A Multicentre Study of Arabian Gulf States

PubMed Central

Daoulah, Amin; Elkhateeb, Osama E.; Nasseri, S. Ali; Al-Murayeh, Mushabab; Al-kaabi, Salem; Lotfi, Amir; Alama, Mohamed N.; Al-Faifi, Salem M.; Haddara, Mamdouh; Dixon, Ciaran M.; Alzahrani, Ibrahim S.; Alghamdi, Abdullah A.; Ahmed, Waleed; Fathey, Adnan; Haq, Ejazul; Alsheikh-Ali, Alawi A

2017-01-01

Introduction: Coronary artery disease (CAD) is a leading cause of death worldwide. The association of socioeconomic status with CAD is supported by numerous epidemiological studies. Whether such factors also impact the number of diseased coronary vessels and its severity is not well established. Materials and Methods: We conducted a prospective multicentre, multi-ethnic, cross sectional observational study of consecutive patients undergoing coronary angiography (CAG) at 5 hospitals in the Kingdom of Saudi Arabia and the United Arab Emirates. Baseline demographics, socioeconomic, and clinical variables were collected for all patients. Significant CAD was defined as ≥70% luminal stenosis in a major epicardial vessel. Left main disease (LMD) was defined as ≥50% stenosis in the left main coronary artery. Multi-vessel disease (MVD) was defined as having >1 significant CAD. Results: Of 1,068 patients (age 59 ± 13, female 28%, diabetes 56%, hypertension 60%, history of CAD 43%), 792 (74%) were from urban and remainder (26%) from rural communities. Patients from rural centres were older (61 ± 12 vs 58 ± 13), and more likely to have a history of diabetes (63 vs 54%), hypertension (74 vs 55%), dyslipidaemia (78 vs 59%), CAD (50 vs 41%) and percutaneous coronary intervention (PCI) (27 vs 21%). The two groups differed significantly in terms of income level, employment status and indication for angiography. After adjusting for baseline differences, patients living in a rural area were more likely to have significant CAD (adjusted OR 2.40 [1.47, 3.97]), MVD (adjusted OR 1.76 [1.18, 2.63]) and LMD (adjusted OR 1.71 [1.04, 2.82]). Higher income was also associated with a higher risk for significant CAD (adjusted OR 6.97 [2.30, 21.09]) and MVD (adjusted OR 2.49 [1.11, 5.56]), while unemployment was associated with a higher risk of significant CAD (adjusted OR 2.21, [1.27, 3.85]). Conclusion: Communal and socioeconomic factors are associated with higher odds of significant CAD and MVD in the group of patients referred for CAG. The underpinnings of these associations (e.g. pathophysiologic factors, access to care, and system-wide determinants of quality) require further study. PMID:28553410

Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study.

PubMed

Barthel, Henryk; Gertz, Hermann-Josef; Dresel, Stefan; Peters, Oliver; Bartenstein, Peter; Buerger, Katharina; Hiemeyer, Florian; Wittemer-Rump, Sabine M; Seibyl, John; Reininger, Cornelia; Sabri, Osama

2011-05-01

Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben (¹⁸F) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben (¹⁸F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben (¹⁸F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18-26, clinical dementia rating [CDR]=0·5-2·0) and age-matched healthy controls (MMSE ≥ 28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84-98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p < 0·0001) compared with the healthy controls, with the posterior cingulate being the best discriminator. Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85% and a specificity of 91%. Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores (r -0·27 to -0·33, p ≤ 0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65%vs 22% [p=0·027] in patients with Alzheimer's disease; 50%vs 16% [p = 0·074] in healthy controls). No safety concerns were noted. We provide verification of the efficacy, safety, and biological relevance of florbetaben (¹⁸F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Bayer Schering Pharma AG. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thromboembolism in Dogs with Protein-Losing Enteropathy with Non-Neoplastic Chronic Small Intestinal Disease.

PubMed

Jacinto, Ana M L; Ridyard, Alison E; Aroch, Itamar; Watson, Penny J; Morrison, Linda R; Chandler, Marge L; Kuzi, Sharon

Dogs with protein-losing enteropathy (PLE) are suggested to be at increased risk of developing thromboembolic events. However, with some exceptions, there are very few reports of thromboembolism in such dogs. This multicentre retrospective observational study describes a case series of thromboembolism (TE) in eight dogs with PLE secondary to non-neoplastic, chronic small intestinal disease. Seven dogs had poorly controlled PLE when the thromboembolic event occurred. Pulmonary thromboembolism (PTE) occurred in six dogs, while one dog developed splenic vein thrombosis and another had concurrent splenic vein and aortic TE. Six dogs died, all with PTE. Antithrombin activity was decreased in one of two dogs in which it was measured. Serum cobalamin and folate concentrations were measured in three dogs and cobalamin was subnormal in all three. Serum magnesium, measured in two dogs, was low in both. Dogs with uncontrolled chronic small intestinal disease and PLE are at risk for developing serious life-threatening TE, mostly PTE.

Phenotypes of organ involvement in sarcoidosis.

PubMed

Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

2018-01-01

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies. Copyright ©ERS 2018.

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

PubMed

Biagi, Federico; Marchese, Alessandra; Ferretti, Francesca; Ciccocioppo, Rachele; Schiepatti, Annalisa; Volta, Umberto; Caio, Giacomo; Ciacci, Carolina; Zingone, Fabiana; D'Odorico, Anna; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Gasbarrini, Antonio; Piscaglia, Anna Chiara; Andrealli, Alida; Astegiano, Marco; Segato, Sergio; Neri, Matteo; Meggio, Alberto; de Pretis, Giovanni; De Vitis, Italo; Gobbi, Paolo; Corazza, Gino Roberto

2014-08-07

Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

[Effects of Behaviour-oriented Exercise Interventions as Supplement within Structured Health-care Programmes for Diabetes Mellitus Type 2 - A Quasi-experimental Multicentre Intervention Study].

PubMed

Eckert, K; Lange, M

2016-06-01

Exercise programs do not belong to standard treatment within disease management programmes for diabetes mellitus type 2, up to now. For these reason the effects of a 10-week behaviour-oriented exercise programme have been evaluated focusing on change in activity behaviour and health-related qualitiy of life. 202 patients took part in the investigation. There were significant inbetween group differences in some aspects of the outcome parameters. The study presents useful information on how to modify existing DMPs successfully for improving patient treatment. © Georg Thieme Verlag KG Stuttgart · New York.

JenaValve.

PubMed

Treede, Hendrik; Rastan, Ardawan; Ferrari, Markus; Ensminger, Stephan; Figulla, Hans-Reiner; Mohr, Friedrich-Wilhelm

2012-09-01

The JenaValve is a next-generation TAVI device which consists of a well-proven porcine root valve mounted on a low-profile nitinol stent. Feeler guided positioning and clip fixation on the diseased leaflets allow for anatomically correct implantation of the device without rapid pacing. Safety and efficacy of transapical aortic valve implantation using the JenaValve were evaluated in a multicentre prospective study that showed good short and midterm results. The valve was CE-mark released in Europe in September 2011. A post-market registry ensures on-going and prospective data collection in "real-world" patients. The transfemoral JenaValve delivery system will be evaluated in a first-in-man study in the near future.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

PubMed Central

Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

2014-01-01

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study)

PubMed Central

Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru; Nishimura, Ataru; Kurogi, Ryota; Sayama, Tetsuro; Iihara, Koji

2016-01-01

Objectives To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Design Retrospective, multicentre, non-randomised, observational study. Setting Nationwide registry data in Japan. Participants A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. Main outcome measure We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Results Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Conclusions Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease. PMID:27008684

Multiple intraosseous hemangiomas-investigation and role of N-butylcyanoacrylate in management.

PubMed

Syal, Rajan; Tyagi, Isha; Goyal, Amit; Barai, Sukanto; Parihar, Anit

2007-05-01

Primary intraosseous hemangiomas are rare (0.7% of all osseous neoplasms), benign, slow-growing neoplasms. These lesions are usually solitary. We are reporting a case of multicentric intraosseous hemangiomas. Investigation, treatment options, and role of N-butylcyanoacrylate (NBCA) in management will be discussed. A 20-year-old man had multicentric intraosseous hemangiomas involving the skull bones, mandible, vertebra, pelvic bone, and tibial tuberosity. N-butylcyanoacrylate was used by direct puncture technique using a transosseous transcutaneous route to control profuse bleeding from the retromolar region. To the best of our knowledge, this is the first reported case with such extensive multicentric intraosseous hemangiomas. N-butylcyanoacrylate by direct puncture technique can be an effective method to devascularize and stabilize low-flow intraosseous vascular tumors. (c) 2007 Wiley Periodicals, Inc.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

Invasive Paget Disease of the Vulva.

PubMed

Borghi, Chiara; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Perotto, Stefania; Leone Roberti Maggiore, Umberto; Recalcati, Dario; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV.

The foundation of NCVD PCI Registry: the Malaysia's first multi-centre interventional cardiology project.

PubMed

Liew, H B; Rosli, M A; Wan Azman, W A; Robaayah, Z; Sim, K H

2008-09-01

The National Cardiovascular Database for Percutaneous Coronary Intervention (NCVD PCI) Registry is the first multicentre interventional cardiology project, involving the main cardiac centres in the country. The ultimate goal of NCVD PCI is to provide a contemporary appraisal of PCI in Malaysia. This article introduces the foundation, the aims, methodology, database collection and preliminary results of the first six-month database.

CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial.

PubMed

2015-06-13

The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590. Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassified the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0·0001). Although both the certainty (relative risk [RR] 2·56, 95% CI 2·33-2·79; p<0·0001) and frequency of coronary heart disease increased (1·09, 1·02-1·17; p=0·0172), the certainty increased (1·79, 1·62-1·96; p<0·0001) and frequency seemed to decrease (0·93, 0·85-1·02; p=0·1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%; p<0·0001) and treatments (23% vs 5%; p<0·0001) but did not affect 6-week symptom severity or subsequent admittances to hospital for chest pain. After 1·7 years, CTCA was associated with a 38% reduction in fatal and non-fatal myocardial infarction (26 vs 42, HR 0·62, 95% CI 0·38-1·01; p=0·0527), but this was not significant. In patients with suspected angina due to coronary heart disease, CTCA clarifies the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funded the trial with supplementary awards from Edinburgh and Lothian's Health Foundation Trust and the Heart Diseases Research Fund. Copyright © 2015 Newby et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

PubMed

Jefferson, Laura; Cook, Liz; Keding, Ada; Brealey, Stephen; Handoll, Helen; Rangan, Amar

2015-11-06

'Away Days' (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multi-centre randomised controlled trials (RCTs). We explored the use of Away Days in multi-centre RCTs and analysed the effect on patient recruitment in a case study. Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multi-centre pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. A total of 94 people responded to the survey. The majority (78%), who confirmed had organised an Away Day previously, found them to be useful. This is despite their costs.. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multi-centre surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study.

PubMed

Wolf, Eva-Maria; Plieschnegger, Wolfgang; Geppert, Michael; Wigginghaus, Bernd; Höss, Gabriele M; Eherer, Andreas; Schneider, Nora I; Hauer, Almuthe; Rehak, Peter; Vieth, Michael; Langner, Cord

2014-05-01

Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses. A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System. Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals. Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Crisaborole Ointment 2%: A Review in Mild to Moderate Atopic Dermatitis.

PubMed

Hoy, Sheridan M

2017-12-01

Crisaborole ointment 2% (Eucrisa™) is a novel, anti-inflammatory inhibitor of phosphodiesterase 4 (PDE4) that is available in the USA for the topical treatment of mild to moderate atopic dermatitis in patients aged ≥ 2 years. In two short-term (28 days), identically designed, multicentre, phase III studies in this patient population, topical therapy with crisaborole ointment 2% reduced disease severity and pruritus severity compared with vehicle, with the effect established early and sustained over the course of treatment. Improvements in the other signs of atopic dermatitis (erythema, exudation, excoriation, induration/papulation, and lichenification) were also seen. Crisaborole ointment 2% was generally well tolerated in the short-term studies, with its favorable safety profile maintained over the longer term (up to 52 weeks) in a multicentre, extension study. Most treatment-emergent adverse events (TEAEs) were of mild to moderate severity and considered unrelated to the study medication. Moreover, the incidence of application-site pain following short- and longer-term topical therapy with crisaborole ointment 2% was low. In conclusion, crisaborole ointment 2% is an effective and generally well tolerated new topical option for the management of mild to moderate atopic dermatitis in patients aged ≥ 2 years, with the potential to effectively treat this patient population over the longer term without the safety concerns associated with other current topical anti-inflammatory agents.

Effect of family nursing therapeutic conversations on health-related quality of life, self-care and depression among outpatients with heart failure: A randomized multi-centre trial.

PubMed

Østergaard, Birte; Mahrer-Imhof, Romy; Wagner, Lis; Barington, Torben; Videbæk, Lars; Lauridsen, Jørgen

2018-03-07

To evaluate the short-term (3 months) effects of family nursing therapeutic conversations (FNTC) on health-related quality of life, self-care and depression in outpatients with Heart failure (HF). A randomised multi-centre trial was conducted in three Danish HF clinics. The control group (n = 167) received usual care, and the intervention group (n = 180) received FNTCs as supplement to usual care. Primary outcome was clinically significant changes (6 points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between groups. Secondary outcomes were changes in self-care behaviour and depression scores. Data were assessed before first consultation and repeated after three months. No statistically significant difference was found in the change of KCCQ, self-care and depression scores between the groups. KCCQ scores of patients in the FNTC group changed clinically significant in seven domains, compared to one domain in the control group, with the highest improvement in self-efficacy, social limitation and symptom burden. FNTC was not superior to standard care of patients with HF regarding health-related quality of life, self-care and depression. Addressing the impact of the disease on the family, might improve self-efficacy, social limitation and symptom burden in patients with heart failure. Copyright © 2018 Elsevier B.V. All rights reserved.

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma.

PubMed

Rebhun, R B; Kent, M S; Borrofka, S A E B; Frazier, S; Skorupski, K; Rodriguez, C O

2011-03-01

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01). © 2010 Blackwell Publishing Ltd.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review

PubMed Central

DÍAZ-DELGADO, Josué; POOL, Roy; HOPPES, Sharman; CEREZO, Argine; QUESADA-CANALES, Óscar; STOICA, George

2017-01-01

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies. PMID:28331115

FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort.

PubMed

Caminiti, Silvia Paola; Ballarini, Tommaso; Sala, Arianna; Cerami, Chiara; Presotto, Luca; Santangelo, Roberto; Fallanca, Federico; Vanoli, Emilia Giovanna; Gianolli, Luigi; Iannaccone, Sandro; Magnani, Giuseppe; Perani, Daniela

2018-01-01

In this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to Alzheimer's disease (AD) dementia and non-AD dementias. We included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as "typical-AD", "atypical-AD" (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), "non-AD" (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or "negative" patterns. To perform the statistical analyses, the individual patterns were grouped either as "AD dementia vs. non-AD dementia (all diseases)" or as "FTD vs. non-FTD (all diseases)". Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated. The multivariate logistic model identified FDG-PET "AD" SPM classification (Expβ = 19.35, 95% C.I. 4.8-77.8, p < 0.001) and CSF Aβ42 (Expβ = 6.5, 95% C.I. 1.64-25.43, p < 0.05) as the best predictors of conversion from MCI to AD dementia. The "FTD" SPM pattern significantly predicted conversion to FTD dementias at follow-up (Expβ = 14, 95% C.I. 3.1-63, p < 0.001). Overall, FDG-PET-SPM classification was the most accurate biomarker, able to correctly differentiate either the MCI subjects who converted to AD or FTD dementias, and those who remained stable or reverted to normal cognition (Expβ = 17.9, 95% C.I. 4.55-70.46, p < 0.001). Our results support the relevant role of FDG-PET-SPM classification in predicting progression to different dementia conditions in prodromal MCI phase, and in the exclusion of progression, outperforming CSF biomarkers.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

PubMed Central

Luján-Sanchis, Marisol; Pérez-Cuadrado-Robles, Enrique; García-Lledó, Javier; Juanmartiñena Fernández, José-Francisco; Elli, Luca; Jiménez-García, Victoria-Alejandra; Egea-Valenzuela, Juan; Valle-Muñoz, Julio; Carretero-Ribón, Cristina; Fernández-Urién-Sainz, Ignacio; López-Higueras, Antonio; Alonso-Lázaro, Noelia; Sanjuan-Acosta, Mileidis; Sánchez-Ceballos, Francisco; Rosa, Bruno; González-Vázquez, Santiago; Branchi, Federica; Ruano-Díaz, Lucía; Prieto-de-Frías, César; Pons-Beltrán, Vicente; Borque-Barrera, Pilar; González-Suárez, Begoña; Xavier, Sofía; Argüelles-Arias, Federico; Herrerías-Gutiérrez, Juan-Manuel; Pérez-Cuadrado-Martínez, Enrique; Sempere-García-Argüelles, Javier

2017-01-01

AIM To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD. PMID:28216978

The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study.

PubMed

Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie

2015-03-14

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

PubMed

Weis, S; Hagel, S; Schmitz, R P H; Scherag, A; Brunkhorst, F M; Forstner, C; Löffler, B; Pletz, M W

2017-04-08

Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. DRKS00010135. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).

PubMed

Venkatesh, Veena; Kulkarni, K P

2008-12-01

The most common cause of gastroparesis is diabetes mellitus. The present study was carried out to asses the combination of itopride and pantoprazole in the treatment of diabetic gastroparesis. The study was an open label, multicentre, conducted in 743 patients with diabetic gastroparesis for a period of 3 weeks. The efficacy parameters included nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and regurgitation. The patients were evaluated based on the frequency and severity of symptoms and compared with the baseline scores. There were significant improvement in severity as well as the frequency of all the symptom parameters of the disease (p<0.001). The physicians' evaluation to the therapy was rated either excellent or good.

Yeast killer systems.

PubMed Central

Magliani, W; Conti, S; Gerloni, M; Bertolotti, D; Polonelli, L

1997-01-01

The killer phenomenon in yeasts has been revealed to be a multicentric model for molecular biologists, virologists, phytopathologists, epidemiologists, industrial and medical microbiologists, mycologists, and pharmacologists. The surprisingly widespread occurrence of the killer phenomenon among taxonomically unrelated microorganisms, including prokaryotic and eukaryotic pathogens, has engendered a new interest in its biological significance as well as its theoretical and practical applications. The search for therapeutic opportunities by using yeast killer systems has conceptually opened new avenues for the prevention and control of life-threatening fungal diseases through the idiotypic network that is apparently exploited by the immune system in the course of natural infections. In this review, the biology, ecology, epidemiology, therapeutics, serology, and idiotypy of yeast killer systems are discussed. PMID:9227858

Update in inclusion body myositis

PubMed Central

Machado, Pedro; Brady, Stefen; Hanna, Michael G.

2013-01-01

Purpose of review The purpose of this study is to review recent scientific advances relating to the natural history, cause, treatment and serum and imaging biomarkers of inclusion body myositis (IBM). Recent findings Several theories regarding the aetiopathogenesis of IBM are being explored and new therapeutic approaches are being investigated. New diagnostic criteria have been proposed, reflecting the knowledge that the diagnostic pathological findings may be absent in patients with clinically typical IBM. The role of MRI in IBM is expanding and knowledge about pathological biomarkers is increasing. The recent description of autoantibodies to cytosolic 5′ nucleotidase 1A in patients with IBM is a potentially important advance that may aid early diagnosis and provides new evidence regarding the role of autoimmunity in IBM. Summary IBM remains an enigmatic and often misdiagnosed disease. The pathogenesis of the disease is still not fully understood. To date, pharmacological treatment trials have failed to show clear efficacy. Future research should continue to focus on improving understanding of the pathophysiological mechanisms of the disease and on the identification of reliable and sensitive outcome measures for clinical trials. IBM is a rare disease and international multicentre collaboration for trials is important to translate research advances into improved patient outcomes. PMID:24067381

Seroprevalence of five neglected parasitic diseases among immigrants accessing five infectious and tropical diseases units in Italy: a cross-sectional study.

PubMed

Martelli, G; Di Girolamo, C; Zammarchi, L; Angheben, A; Morandi, M; Tais, S; Degani, M; El Hamad, I; Caligaris, S; Ciannameo, A; Grilli, E; Urbinati, L; Monteiro, G B; Scarcella, C; Petrosillo, N; Digaetano, M; Rabbi, L; Bazzanini, N; Cacciatore, F; Marta, B L; Moro, M L; Bartoloni, A; Viale, P; Verucchi, G

2017-05-01

This multicentre cross-sectional study aims to estimate the prevalence of five neglected tropical diseases (Chagas disease, filariasis, schistosomiasis, strongyloidiasis and toxocariasis) among immigrants accessing health care facilities in five Italian cities (Bologna, Brescia, Florence, Rome, Verona). Individuals underwent a different set of serological tests, according to country of origin and presence of eosinophilia. Seropositive patients were treated and further followed up. A total of 930 adult immigrants were enrolled: 477 men (51.3%), 445 women (47.9%), eight transgender (0.8%); median age was 37.81 years (range 18-80 years). Most of them had come from the African continent (405/930, 43.5%), the rest from East Europe, South America and Asia, and 9.6% (89/930) were diagnosed with at least one of the infections under study. Seroprevalence of each specific infection varied from 3.9% (7/180) for Chagas disease to 9.7% (11/113) for toxocariasis. Seropositive people were more likely to be 35-40 years old and male, and to come from South East Asia, sub-Saharan Africa or South America. The results of our study confirm that neglected tropical diseases represent a substantial health problem among immigrants and highlight the need to address this emerging public health issue. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses

PubMed Central

2014-01-01

Background Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history. PMID:25103857

The challenges of implementing a multi-centre audit of end-of-life care in care homes.

PubMed

Levy, Jean; Kinley, Julie; Conway, Frances

2016-11-02

This article aims to share the experience of a hospice in facilitating a multi-centre audit of end-of-life care in care homes, particularly noting the challenges and enablers of carrying out the audit. The audit was a retrospective multi-centre survey of bereaved relatives/next of kin of residents who died in the care home, using an anonymous, validated questionnaire: the Family Perception of Care Scale. Questionnaires were sent 3-months after bereavement. Returned questionnaires were analysed using SPSS and Excel. The care homes were in areas encompassing outer and inner city populations. The team identified eight challenges to the audit process, in particular, embedding procedures within the care homes, non-responses and developing action plans for improvement. Overall, the audit provided an indication of where improvements could be made and where care was already excellent, built confidence and increased expertise in the care-home staff.

[Relevance of the detection of complex congenital heart disease by screening with pulse oximetry in apparently healthy newborns in health establishments].

PubMed

Jiménez-Carbajal, María Guadalupe; López Pérez, Didier; Fernández Luna, Claudia Paola

2018-03-13

A review is presented of data published in medical literature related to the screening used for the early detection of complex congenital heart disease in apparently healthy newborns in several cities of the world, including those reported in Mexico. The screening was performed due to the knowledge of the pathophysiology of indirect hypoxia data, observation of differential cyanosis and the consequent difference in the values of pre- and post-ductal pulse oximetry derived from the ductal and/or atrial septal defect dependence of several severe congenital heart diseases. Multicentre research studies have also been carried out on a massive scale, thus justifying the usefulness of the practice for its daily implementation and at international level. Additionally, legislative topics are cited in our country as part of the efforts to establish the mandatory nature of the screening throughout the Mexican Republic. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

PubMed Central

Coen, Natacha; Duraffour, Sophie; Snoeck, Robert; Andrei, Graciela

2014-01-01

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely efficacious. As the majority of tumor cells are latently infected with KSHV, currently marketed antivirals that target the virus lytic cycle have shown inconsistent results in clinic. Nevertheless, lytic replication plays a major role in disease progression and virus dissemination. Case reports and retrospective studies have pointed out the benefit of antiviral therapy in the treatment and prevention of KSHV-associated diseases. As a consequence, potent and selective antivirals are needed. This review focuses on the anti-KSHV activity, mode of action and current status of antiviral drugs targeting KSHV lytic cycle. Among these drugs, different subclasses of viral DNA polymerase inhibitors and compounds that do not target the viral DNA polymerase are being discussed. We also cover molecules that target cellular kinases, as well as the potential of new drug targets and animal models for antiviral testing. PMID:25421895

Magnetic resonance mammography in comparison with mammography in the discovery of multifocal, multicentric and bilateral lesions of breast cancer.

PubMed

Bakhtavar, Khadijeh; Saran, Maryam; Behzadifar, Masoud; Farsi, Maryam

2017-08-01

Breast cancer is one of the health system problems and important diseases that is rising in developing and advanced countries. This study aimed to determine the difference of Magnetic Resonance Mammography (MRM) findings versus mammography in detecting multifocal, multi-centric and malignant bilateral lesions in patients with known breast cancer in Tehran. This cross-sectional study was conducted in Iran and Tehran among breast cancer patients between January 2015 and February 2016. Patients were included in the study prior to surgery, at the request of a surgeon with the aim of detecting multifocal, multi-centric and bilateral lesions. Demographic information was also collected from patients. The results for quantitative variables were expressed as mean and standard deviations, and for qualitative variables, were expressed as relative and absolute frequency. Chi-square test was used to compare the two methods. SPSS Ver.24 (IBM) software was used to analyze the data. Thirty-nine patients were enrolled in the study. The mean age of patients in this study was 48.46±6.836. In mammography, 13 (33.3%) had Composition C and 26 (66.7%) had Composition D according to the type of Composition. In total, 25 patients (89.3%) had one lesion and 3 patients (10.7%) had more than two lesions. In MRM, all lesions observed were mass (54 masses). The number of lesions found in MRM was 27 patients with one lesion (58.9%), 6 patients with two lesions (20.5%) and 5 patients with three lesions (20.6%). MRM detected more lesions compared to mammography (p<0.0001). The value of Chi-square test with a degree of freedom and error level of 0.05 was 3.71 and p<0.0001 that showed a significant relationship between the number of MRM findings in comparison with mammography. The results of our study showed that two or more lesions and bilateral lesions in MRM were more than mammography in women with B Breast Composition C, D; the findings showed that MRM has a better ability to detect breast masses, and can affect the patient's surgical procedure.

Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation.

PubMed

Bourbeau, Jean; Lavoie, Kim L; Sedeno, Maria; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

2016-04-04

Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations. NCT02085161. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study)

PubMed Central

2014-01-01

Background Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. Methods/Design In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia. Trail registration number NCT01927497 (Clinicaltrial.gov). PMID:25163547

Takayasu arteritis in childhood: misdiagnoses at disease onset and associated diseases.

PubMed

Clemente, Gleice; Silva, Clovis A; Sacchetti, Silvana B; Ferriani, Virginia P L; Oliveira, Sheila K; Sztajnbok, Flavio; Bica, Blanca E R G; Cavalcanti, André; Robazzi, Teresa; Bandeira, Marcia; Terreri, Maria Teresa

2018-06-01

Juvenile-Takayasu arteritis (j-TA) is a difficult diagnosis and some patients develop uncommon manifestations and associated diseases that may contribute to the delayed diagnosis. Our aim was to identify the misdiagnoses, the associated diseases and the atypical manifestations observed in a j-TA Brazilian multicentre study. 71 children and adolescents who met the classification criteria for j-TA were included. The misdiagnoses, the associated diseases and the atypical manifestations were evaluated. 19 (26.8%) patients had misdiagnoses. The most common of them was aortic coarctation in six (8.4%) patients, followed by rheumatic fever in five (7.0%) and one patient presented with both former diagnoses. Limb pain (two patients), spondyloarthropathy, juvenile idiopathic arthritis (JIA), spinal arteriovenous malformation, polyarteritis nodosa (PAN) and fever of unknown origin (FUO) were other misdiagnoses. Patients who had misdiagnoses previously to j-TA diagnosis presented a trend to have a longer diagnosis delay. 11 (15.5%) patients had 14 TA-associated diseases, such as pulmonary tuberculosis (5 patients), rheumatic fever (2 patients), spondyloarthropathy, polyarticular JIA, Crohn's disease, Prader-Willi disease, diabetes mellitus, Moyamoya and primary immunodeficiency. 7 (9.9%) patients presented 10 atypical manifestations, such as pyoderma gangrenosum, erythema nodosum, myositis, chorea, enthesitis, episcleritis, uveitis, hepatomegaly, splenomegaly and necrosis of extremities. Our study emphasizes the main misdiagnoses, associated diseases and atypical manifestations that occur in patients with j-TA and warns of the features that may alert paediatricians to this diagnosis, such as constitutional symptoms and elevated inflammatory markers.

Sociodemographic profile of children with Kawasaki disease in North India.

PubMed

Prakash, Jeya; Singh, Surjit; Gupta, Anju; Bharti, Bhavneet; Bhalla, A K

2016-03-01

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

PubMed

Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

2017-11-01

The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

Are power calculations useful? A multicentre neuroimaging study

PubMed Central

Suckling, John; Henty, Julian; Ecker, Christine; Deoni, Sean C; Lombardo, Michael V; Baron-Cohen, Simon; Jezzard, Peter; Barnes, Anna; Chakrabarti, Bhismadev; Ooi, Cinly; Lai, Meng-Chuan; Williams, Steven C; Murphy, Declan GM; Bullmore, Edward

2014-01-01

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. PMID:24644267

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

PubMed

De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

2016-08-01

The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

PubMed

van Roozendaal, L M; Vane, M L G; van Dalen, T; van der Hage, J A; Strobbe, L J A; Boersma, L J; Linn, S C; Lobbes, M B I; Poortmans, P M P; Tjan-Heijnen, V C G; Van de Vijver, K K B T; de Vries, J; Westenberg, A H; Kessels, A G H; de Wilt, J H W; Smidt, M L

2017-07-01

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Protocol for a multicentred randomised controlled trial investigating the use of personalised golimumab dosing tailored to inflammatory load in ulcerative colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis) led by the INITIAtive group (NCT 0268772)

PubMed Central

Sheridan, Juliette; Coe, Carol Ann; Doran, Peter; Egan, Laurence; Cullen, Garret; Kevans, David; Leyden, Jan; Galligan, Marie; O’Toole, Aoibhlinn; McCarthy, Jane; Doherty, Glen

2018-01-01

Introduction Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC. The design of GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal DL or persisting inflammatory burden as represented by raised faecal calprotectin (FCP). Aim The primary aim of the study is to ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during maintenance) improves rates of patient continuous clinical response and reduces disease activity in UC. Methods and analysis A randomised, multicentred two-arm trial studying the effect of dose optimisation of GLM based on FCP and DL versus treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1 of 2 treatment groups and shall be treated over a period of 46 weeks. Ethics and dissemination The study protocol was approved by the Research Ethics committee of St. Vincent’s University Hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial registration numbers EudraCT number: 2015-004724-62; Clinicaltrials.gov Identifier: NCT0268772; Pre-results. PMID:29379609

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

PubMed

Thibault, Vincent; Gaudy-Graffin, Catherine; Colson, Philippe; Gozlan, Joël; Schnepf, Nathalie; Trimoulet, Pascale; Pallier, Coralie; Saune, Karine; Branger, Michel; Coste, Marianne; Thoraval, Francoise Roudot

2013-03-15

Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.

Transcatheter Closure of Patent Foramen Ovale in Patients with Platypnea-Orthodeoxia: Results of a Multicentric French Registry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerin, P.; Lambert, V.; Godart, F.

Background. Dyspnea and the decrease in arterial saturation in the upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS). POS is secondary to the occurrence of an atrial right-to-left shunt through a patent foramen ovale (PFO). Methods. This French multicentric study reports on 78 patients (mean age 67 {+-} 11.3 years) with POS who had transcatheter closure of the PFO; frequently associated diseases were pneumonectomy (n = 36) and an ascending aortic aneurysm (n = 11). In all patients, the diagnosis was confirmed by transthoracic or/and transesophageal echocardiography. Five different closure devices were used: Amplatz (n = 45),more » Cardioseal (n = 13), Sideris (n = 11), Das Angel Wings (n = 8) and Starflex (n = 1). Closure was successful in 76 patients (97%). Results. Oxygen saturation increased immediately after occlusion from 84.6 {+-} 10.7% to 95.1 {+-} 6.4% (p < 0.001) and dyspnea improved from grade 2.7 {+-} 0.7 to grade 1 {+-} 1 (p < 0.001). A small residual shunt was immediately observed in 5 patients (3 with the Cardioseal device, 1 with the Sideris and 1 with the Amplatz) leading to the implantation of a second device in one case (Cardioseal). Two early deaths occurred unrelated to the procedure (one due to sepsis probably related to pneumonectomy, another due to respiratory insufficiency). Other complications were: a small shunt between the aorta and the left atrium, two atrial fibrillations and a left-sided thrombus which disappeared with anticoagulant therapy. At a mean follow-up of 15 {+-} 12 months, there were 7 late deaths related to the underlying disease. Conclusion. Percutaneous occlusion of the foramen ovale is safe and gives excellent results thanks to continuing improvement in available devices. This technique enables some patients in an unstable condition to avoid a surgical closure.« less

Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

PubMed

Esteves, F; de Sousa, B; Calderón, E J; Huang, L; Badura, R; Maltez, F; Bassat, Q; de Armas, Y; Antunes, F; Matos, O

2016-06-01

Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Twelve-month results of a prospective, multicentre trial to assess the everolimus-eluting coronary stent system (PROMUS Element): the PLATINUM PLUS all-comers randomised trial.

PubMed

Fajadet, Jean; Neumann, Franz-Josef; Hildick-Smith, David; Petronio, Sonia; Zaman, Azfar; Spence, Mark; Wöhrle, Jochen; Elhadad, Simon; Roberts, David; Hovasse, Thomas; Valdés, Mariano; Silber, Sigmund

2017-01-20

The aim of the study was to compare the safety and efficacy of the platinum-chromium-based everolimus-eluting stent (EES) with a cobalt-chromium EES. We performed a prospective, multicentre, single-blind non-inferiority all-comers study randomising patients with stable or unstable coronary artery disease (2:1) to treatment with the platinum-chromium EES (n=1,952) or the control cobalt-chromium EES (n=1,028) in Europe (PLATINUM PLUS trial). The primary endpoint was target vessel failure (TVF) at 12 months, a composite of target vessel-related cardiac death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (TVR). Among 2,980 patients, 33% presented with acute coronary syndromes, and 48% with multivessel disease. At 12 months, the intention-to-treat analysis determined that the platinum-chromium EES was non-inferior to the cobalt-chromium EES for the primary endpoint (86 [4.6%] patients vs. 32 [3.2%], absolute difference 1.4%, 95% confidence interval [CI]: -0.1-2.9; upper limit of the one-sided 95% CI: 2.57%; non-inferiority p=0.012; superiority analysis: hazard ratio [HR] 1.44, 95% CI: 0.96-2.16, p=0.08). In the per protocol analysis, however, the primary endpoint was significantly more common in the platinum-chromium EES (HR 1.64, 95% CI: 1.05-2.55, p=0.03). There were no significant differences in the rates of cardiac death (1.1% vs. 1.0%, p=0.78), MI (1.6% vs. 0.8%, p=0.09), or ischaemia-driven TLR (2.0% vs. 1.6%, p=0.49). The rates of ARC definite or probable stent thrombosis were comparable between platforms (0.8% vs. 0.5%, p=0.44). At one year, the platinum-chromium EES satisfied the pre-specified criteria for non-inferiority relative to the control cobalt-chromium EES in this all-comers trial.

NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study.

PubMed

Schoonbeek, R C; Pieper, P G; van Slooten, Y J; Freling, H G; Sieswerda, G T; van Dijk, A P J; Jongbloed, M R M; Post, M C; Bouma, B J; Berger, R M F; Ebels, T; van Melle, J P

2016-11-01

N-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity. In this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO 2 peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves). A total of 306 ACHD patients with pulmonary valve replacement (PVR, n = 139), aortic valve replacement (n = 141), mitral valve replacement (n = 21) or tricuspid valve replacement (n = 5) were investigated. The majority of patients (77 %) were in NYHA class I or II. Elevated NT-proBNP levels (cut-off ≥125 pg/ml) were found in 50 % of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (p = 0.029) and VO 2 max (p < 0.001). In PVR patients, NT-proBNP levels were associated with lower VO 2 peak, also after adjustment for age, gender and age at valve replacement in a multivariate model (p = 0.015). In patients with ACHD and a prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, a higher NT-proBNP level was associated with a lower VO 2 peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

PubMed

Meulenbroek, Olga; O'Dwyer, Sarah; de Jong, Daan; van Spijker, Gerrita; Kennelly, Sean; Cregg, Fiona; Olde Rikkert, Marcel; Abdullah, Laila; Wallin, Anders; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Daly, Leslie; Segurado, Ricardo; Borjesson-Hanson, Anne; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Molloy, William; Tsolaki, Magda; Howard, Robert; Adams, Jessica; Gaynor, Siobhan; Lawlor, Brian

2016-07-19

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. EUDRACT 2012-002764-27; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study.

PubMed

Mackenzie, Isla S; Ford, Ian; Walker, Andrew; Hawkey, Chris; Begg, Alan; Avery, Anthony; Taggar, Jaspal; Wei, Li; Struthers, Allan D; MacDonald, Thomas M

2016-09-08

Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups. 32017426, pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Evaluation of tularaemia courses: a multicentre study from Turkey.

PubMed

Erdem, H; Ozturk-Engin, D; Yesilyurt, M; Karabay, O; Elaldi, N; Celebi, G; Korkmaz, N; Guven, T; Sumer, S; Tulek, N; Ural, O; Yilmaz, G; Erdinc, S; Nayman-Alpat, S; Sehmen, E; Kader, C; Sari, N; Engin, A; Cicek-Senturk, G; Ertem-Tuncer, G; Gulen, G; Duygu, F; Ogutlu, A; Ayaslioglu, E; Karadenizli, A; Meric, M; Ulug, M; Ataman-Hatipoglu, C; Sirmatel, F; Cesur, S; Comoglu, S; Kadanali, A; Karakas, A; Asan, A; Gonen, I; Kurtoglu-Gul, Y; Altin, N; Ozkanli, S; Yilmaz-Karadag, F; Cabalak, M; Gencer, S; Umut Pekok, A; Yildirim, D; Seyman, D; Teker, B; Yilmaz, H; Yasar, K; Inanc Balkan, I; Turan, H; Uguz, M; Kilic, S; Akkoyunlu, Y; Kaya, S; Erdem, A; Inan, A; Cag, Y; Bolukcu, S; Ulu-Kilic, A; Ozgunes, N; Gorenek, L; Batirel, A; Agalar, C

2014-12-01

In this multicentre study, which is the largest case series ever reported, we aimed to describe the features of tularaemia to provide detailed information. We retrospectively included 1034 patients from 41 medical centres. Before the definite diagnosis of tularaemia, tonsillitis (n = 653, 63%) and/or pharyngitis (n = 146, 14%) were the most frequent preliminary diagnoses. The most frequent clinical presentations were oropharyngeal (n = 832, 85.3%), glandular (n = 136, 13.1%) and oculoglandular (n = 105, 10.1%) forms. In 987 patients (95.5%), the lymph nodes were reported to be enlarged, most frequently at the cervical chain jugular (n = 599, 58%), submandibular (n = 401, 39%), and periauricular (n = 55, 5%). Ultrasound imaging showed hyperechoic and hypoechoic patterns (59% and 25%, respectively). Granulomatous inflammation was the most frequent histological finding (56%). The patients were previously given antibiotics for 1176 episodes, mostly with β-lactam/β-lactamase inhibitors (n = 793, 76%). Antituberculosis medications were provided in seven (2%) cases. The patients were given rational antibiotics for tularaemia after the start of symptoms, with a mean of 26.8 ± 37.5 days. Treatment failure was considered to have occurred in 495 patients (48%). The most frequent reasons for failure were the production of suppuration in the lymph nodes after the start of treatment (n = 426, 86.1%), the formation of new lymphadenomegalies under treatment (n = 146, 29.5%), and persisting complaints despite 2 weeks of treatment (n = 77, 15.6%). Fine-needle aspiration was performed in 521 patients (50%) as the most frequent drainage method. In conclusion, tularaemia is a long-lasting but curable disease in this part of the world. However, the treatment strategy still needs optimization. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

PubMed

Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

2015-02-01

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial.

PubMed

Ohguri, Takayuki; Harima, Yoko; Imada, Hajime; Sakurai, Hideyuki; Ohno, Tatsuya; Hiraki, Yoshiyuki; Tuji, Koh; Tanaka, Masahiro; Terashima, Hiromi

2018-06-01

To evaluate the contribution of the thermal dose parameters during regional hyperthermia (HT) treatment to the clinical outcomes in patients with cervical carcinoma (CC) who received chemoradiotherapy (CRT) plus HT. Data from a multicentre randomised clinical trial of concurrent CRT + HT vs. CRT alone were used to evaluate the efficacy and safety of this combination therapy in the CC patients. The intrarectal temperatures of patients undergoing HT were recorded. The complete thermal data of 47 (92%) of the 51 patients in the CRT + HT group were available for the thermal analysis. Thus, 47 patients who received CRT + HT were included in the present study. Among the patients who received CRT + HT, a higher CEM43T90 (≥1 min) value (a thermal dose parameter) was significantly associated with better local relapse-free survival in both univariate (p = 0.024) and multivariate (p = 0.0097) analyses. The disease-free survival of the patients with higher CEM43T90 (≥1 min) values tended to be better in comparison to patients with lower CEM43T90 (<1 min) value (p = 0.071). A complete response tended to be associated with the CEM43T90 (p = 0.056). Disease-free survival, local relapse-free survival and complete response rate for patients with higher CEM43T90 (≥1) were significantly better than those for patients with CRT alone (p = 0.036, p = 0.036 and p = 0.048). Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial

PubMed Central

Ross, J D C; Cronjé, H S; Paszkowski, T; Rakoczi, I; Vildaite, D; Kureishi, A; Alefelder, M; Arvis, P; Reimnitz, P

2006-01-01

Objective This multinational, multicentre, prospective, randomised, double blind, parallel group, non‐inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. Methods Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). Results Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5–24 days post‐therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: −5.7% to 4.0%). At follow up (28–42 days post‐therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: −8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: −8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). Conclusion In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events. PMID:16723364

Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study.

PubMed

Wraith, J E; Guffon, N; Rohrbach, M; Hwu, W L; Korenke, G C; Bembi, B; Luzy, C; Giorgino, R; Sedel, F

2009-11-01

Niemann-Pick disease type C (NP-C) is a devastating genetic disorder characterised by progressive neurological deterioration. However, data on the progression of neurological manifestations, particularly across different patient age-of-disease onsets, are limited. This is an observational retrospective cohort study designed to assess the progression of neurological disease in patients with NP-C. Physicians were asked to retrospectively complete a web-based questionnaire for each patient, at diagnosis and at up to three follow-up visits. An NP-C-specific disability scale was used to measure disease progression. The scale comprised four key parameters of neurological disease progression; ambulation, manipulation, language and swallowing. Disease progression was evaluated based on the annual rate of change in each parameter and the composite score using a linear mixed model analysis, and by classifying patients according to the number of worsened parameters during the observation period. Data were collected from 57 patients. The rate of deterioration was similar across the four individual parameters of the disability scale. The mean (95% CI) annual disease progression was +0.12 (0.09, 0.15) units. Among patients with a time interval of at least 1 year between diagnosis and last visit (n=49), 42 (86%) patients had progressed disease and 7 (14%) patients had stable disease. Disease progression was consistently more rapid in patients diagnosed in early childhood, compared with those diagnosed in late childhood, or with juvenile or adult presentation. In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations.

Establishing a national knowledge translation and generation network in kidney disease: the CAnadian KidNey KNowledge TraNslation and GEneration NeTwork.

PubMed

Manns, Braden; Barrett, Brendan; Evans, Michael; Garg, Amit; Hemmelgarn, Brenda; Kappel, Joanne; Klarenbach, Scott; Madore, Francois; Parfrey, Patrick; Samuel, Susan; Soroka, Steven; Suri, Rita; Tonelli, Marcello; Wald, Ron; Walsh, Michael; Zappitelli, Michael

2014-01-01

Patients with chronic kidney disease (CKD) do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN) guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.

Vitamin D deficiency in inflammatory bowel disease: prevalence and predictors in a Norwegian outpatient population.

PubMed

Frigstad, Svein Oskar; Høivik, Marte; Jahnsen, Jørgen; Dahl, Sandra Rinne; Cvancarova, Milada; Grimstad, Tore; Berset, Ingrid Prytz; Huppertz-Hauss, Gert; Hovde, Øistein; Torp, Roald; Bernklev, Tomm; Moum, Bjørn; Jelsness-Jørgensen, Lars-Petter

2017-01-01

Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD. Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory. In total, 49% (200/408) of the patients had a 25-OH-D concentration <50 nmol/L, including 53% (122/230) of the Crohn's disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >100 mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency. Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Cognitive and emotional factors affecting avoidable decision-making delay in acute myocardial infarction male adults.

PubMed

Vidotto, Giulio; Bertolotti, Giorgio; Zotti, AnnaMaria; Marchi, Stefano; Tavazzi, Luigi

2013-01-01

To study the potentially avoidable decision-making delay in acute myocardial infarction (AMI) adults male with different psychological characteristics a nationwide multicentre study was conducted in Italy by the 118 Coronary Care Units (CCUs). 929 AMI patients consecutively presented to the CCU in a conscious condition less than two hours, 2-6 hours, 6-12 hours, and more than 12 hours after symptom onset and completing the Disease Distress Questionnaire (DDQ) were enrolled in a multicentre case-control study. The DDQ collects information regarding the decision time to seek help, and includes a set of items assessing psychological factors and pain-related symptoms. The relationship between the perceived threat and the delay due to decision-making was evaluated by means of a multivariate model using LISREL 8 structural equation modelling. The delay significantly correlated with perceived threat, which was mainly related to somatic awareness. It was only slightly related to pain and was not associated with any of the other variables. Perceived threat was also related to psychological upset, fear and health worries, the first of which was considerably influenced by emotional instability. Somatic awareness is the main dimension affecting perceived threat, but subjective pain intensity affects the delay both directly and indirectly. The core of the model is the relationship between perceived threat and the delay due to decision-making. The importance of subjective pain intensity is well documented, but it is still not clear how subjective and objective pain interact.

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in north Italy.

PubMed

Casari, S; Suligoi, B; Camoni, L; Pavan, A; Macchi, L; Capelli, M; Paraninfo, G; Compostella, S; Castelli, F; Carosi, G; Donato, F

2012-12-01

We aimed to investigate socio-demographic, clinical and epidemiological characteristics and behaviours of subjects with new HIV diagnosis. We carried out a multi-centre cross-sectional study comprising 17 infectious diseases units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. 472 patients were enrolled (mean age 39.8 years, standard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were heterosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, heterosexual transmission route, and with >10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4+ lymphocyte count >350/microl and self-perception of risk. This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Compared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours.

[A national multicentre study on nosocomial infections in PICU].

PubMed

Jordan García, I; Arriourtúa, A Bustinza; Torre, J A Concha; Antón, J Gil; Vicente, J C de Carlos; González, C Téllez

2014-01-01

Nosocomial infection (NI) is a common complication in paediatric critical care units (PICU), with an associated mortality up to 11%. To describe NI epidemiology in the national PICU. To initiate an standard NI control measures to obtain paediatric incidence rates. Multicentre prospective study from 1 to 31 march 2007. Centre Disease Control diagnosis and methodological criteria were used. It was specially analyzed NI related to invasive devices: central venous catheter (CVC), mechanical ventilation (MV), urinary catheter (UC). There were recruited 300 patients from 6 PICU, with 17 NI episodes in 16 patients (5,3% from admitted). NI rates resulted in 13,8 infections/1000 patients-day. Middle age from infected patients was 2,31 years (± 3,43), 9 males. Risk factors were found in 7 cases. NI location was: catheter-related bloodstream infection in 7 patients (6,7/1000 days CVC), ventilator associated pneumonia in 4 (9,4/1000 MV days), urinary-tract infection associated with UC in 4 (5,5/1000 UC days), one case of primary bloodstream infection and one surgical site infection. Isolated microorganisms were: 9 gram negatives bacillus, 4 Candida, 2 plasmocoagulase negative staphylococcus, 1 Haemophilus and 1 Staphylococcus aureus. Seven isolations were resistant microorganisms. There weren't any died related to NI. NI epidemiology was similar to published data in our near countries. NI surveillance, with a standardized method of analysis is essential to the NI correct manage. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients.

PubMed

Mäurer, M; Ortler, S; Baier, M; Meergans, M; Scherer, P; Hofmann, We; Tracik, F

2013-04-01

Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer's disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function. The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment. Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. In total, 86 patients were enrolled. Patients who received rivastigmine (n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo (n = 38) after 16 weeks of treatment (p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study.

PubMed

Dargère, S; Parienti, J-J; Roupie, E; Gancel, P-E; Wiel, E; Smaiti, N; Loiez, C; Joly, L-M; Lemée, L; Pestel-Caron, M; du Cheyron, D; Verdon, R; Leclercq, R; Cattoir, V

2014-11-01

Detection of microorganisms by blood cultures (BCs) is essential in managing patients with bacteraemia. Rather than the number of punctures, the volume of blood drawn is considered paramount in efficient and reliable detection of microorganisms. We performed a 1-year prospective multicentre study in adult emergency departments of three French university hospitals comparing two methods for BCs: a unique blood culture (UBC) collecting a large volume of blood (40 mL) and the standard method of multiple blood cultures (MBC). The performances of both methods for bacterial contamination and efficient microbial detection were compared, each patient serving as his own control. Amongst the 2314 patients included, three hundred were positive for pathogens (n=245) or contaminants (n=55). Out of the 245 patients, 11 were positive for pathogens by UBC but negative by MBC and seven negative by UBC but positive by MBC (p 0.480). In the subgroup of 137 patients with only two BCs, UBC was superior to MBC (p 0.044). Seven and 17 patients had contaminated BCs by UBC and MBC only, respectively (p 0.062). Considering the sums of pathogens missed and contaminants, UBC significantly outperformed MBC (p 0.045). Considering the complete picture of cost savings, efficient detection of microorganisms and decrease in contaminations, UBC offers an interesting alternative to MBC. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

PubMed

Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

2018-03-01

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

PubMed

Mooney, Peter D; Leeds, John S; Libzo, Nafan; Sidhu, Reina; Evans, Kate E; Hall, Emma J; Jandu, Veerinder S; Hopper, Andrew D; Basumani, Pandurangan; Dear, Keith L; McAlindon, Mark E; Sanders, David S

2014-01-01

Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Multicentre population-based dementia prevalence survey in Japan: a preliminary report.

PubMed

Ikejima, Chiaki; Hisanaga, Akito; Meguro, Kenichi; Yamada, Tatsuo; Ouma, Shinji; Kawamuro, Yu; Hyouki, Kazushi; Nakashima, Kenji; Wada, Kenji; Yamada, Shigeto; Watanabe, Itaru; Kakuma, Tatsuyuki; Aoyama, Yoshiko; Mizukami, Katsuyoshi; Asada, Takashi

2012-06-01

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.

Eating Disorders in Adolescents with Celiac Disease: Influence of Personality Characteristics and Coping.

PubMed

Wagner, Gudrun; Zeiler, Michael; Berger, Gabriele; Huber, Wolf-Dietrich; Favaro, Angela; Santonastaso, Paolo; Karwautz, Andreas

2015-09-01

Patients suffering from celiac disease (CD) have a higher risk of developing disturbed eating behaviour. In a multi-centre study, 259 female adolescents with CD and without a chronic condition were analysed regarding their eating disorder (ED) status, depression, personality, coping strategies and quality of life. Patients with CD and comorbid EDs were older and more often non-compliant with their diet and had a higher body mass index (BMI) and higher levels of depression. Differences in personality features disappear when controlling for age and depression. Higher ill-being and lower joy in life were reported by patients with CD and ED compared with patients without EDs, even when controlling for age and depression levels. No differences between patients (with CD) with and without EDs in coping strategies were found. BMI and lower self-directedness predicted ED status. Early identification of EDs in patients with CD is suggested and should include BMI and personality factors. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

N-acetylcysteine – passe-partout or much ado about nothing?

PubMed Central

Aitio, Mirja-Liisa

2006-01-01

In experimental studies, the old mucolytic agent N-acetylcysteine (NAC) has had beneficial effects in disorders supposedly linked to oxidative stress. Numerous, mainly small clinical trials with variable doses have yielded inconsistent results in a wide variety of diseases. NAC added to the conventional therapy of human immunodeficiency virus infection might be of benefit; in respect of chronic obstructive pulmonary disease, systematic reviews and meta-analyses suggested that prolonged treatment with NAC is efficacious, but a recent multicentre study has questioned this. In a large intervention trial on cancer recurrence, NAC was ineffective. NAC infusions have been widely used in acute hepatic failure but convincing evidence of its benefits is lacking. A preliminary study reported that NAC is effective in preventing radiocontrast-induced nephropathy but thereafter highly mixed results have been published, and even meta-analyses disagree on its efficacy. In intensive care NAC has mostly been a disappointment but recently it has ‘given promises’ in surgery with cardiopulmonary bypass. NAC therapy is routine only in paracetamol intoxication. PMID:16390346

[Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease].

PubMed

Ollat, H; Laurent, B; Bakchine, S; Michel, B-F; Touchon, J; Dubois, B

2007-01-01

The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.

Recent advances in the understanding of severe cutaneous adverse reactions.

PubMed

Adler, N R; Aung, A K; Ergen, E N; Trubiano, J; Goh, M S Y; Phillips, E J

2017-11-01

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients. © 2017 British Association of Dermatologists.

MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

PubMed

Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

2015-12-01

A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort

PubMed Central

Gamundi, Maria José; Duch, Susana; Rios, Jose; Carballo, Miguel; Study Group, EMEIGG

2017-01-01

Introduction The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. Design Retrospective, observational, multicentre, cohort study. Material and Methods The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. Results 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. Conclusions The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment. PMID:29082038

Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

PubMed Central

2015-01-01

Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo groups was −1.12 (80% CI −2.93 to 0.69) and the null hypothesis was rejected in favour of futility (p=0.09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers' only sample, suggested that the 15 mg dose is also futile (p=0.09 for LVCF, p=0.09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0.12 for LVCF, p=0.19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. Interpretation These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in patients with Parkinson's disease is not recommended. Funding National Institute of Neurological Disorders and Stroke. PMID:26116315

Multi-region analysis of longitudinal FDG-PET for the classification of Alzheimer’s disease

PubMed Central

Gray, Katherine R.; Wolz, Robin; Heckemann, Rolf A.; Aljabar, Paul; Hammers, Alexander; Rueckert, Daniel

2012-01-01

Imaging biomarkers for Alzheimer’s disease are desirable for improved diagnosis and monitoring, as well as drug discovery. Automated image-based classification of individual patients could provide valuable diagnostic support for clinicians, when considered alongside cognitive assessment scores. We investigate the value of combining cross-sectional and longitudinal multi-region FDG-PET information for classification, using clinical and imaging data from the Alzheimer’s Disease Neuroimaging Initiative. Whole-brain segmentations into 83 anatomically defined regions were automatically generated for baseline and 12-month FDG-PET images. Regional signal intensities were extracted at each timepoint, as well as changes in signal intensity over the follow-up period. Features were provided to a support vector machine classifier. By combining 12-month signal intensities and changes over 12 months, we achieve significantly increased classification performance compared with using any of the three feature sets independently. Based on this combined feature set, we report classification accuracies of 88% between patients with Alzheimer’s disease and elderly healthy controls, and 65% between patients with stable mild cognitive impairment and those who subsequently progressed to Alzheimer’s disease. We demonstrate that information extracted from serial FDG-PET through regional analysis can be used to achieve state-of-the-art classification of diagnostic groups in a realistic multi-centre setting. This finding may be usefully applied in the diagnosis of Alzheimer’s disease, predicting disease course in individuals with mild cognitive impairment, and in the selection of participants for clinical trials. PMID:22236449

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective.

PubMed

Ezzat, Hanna; Ross, Sue; von Dadelszen, Peter; Morris, Tara; Liston, Robert; Magee, Laura A

2010-07-30

For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review.

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

PubMed

Knapp, Martin; King, Derek; Romeo, Renée; Adams, Jessica; Baldwin, Ashley; Ballard, Clive; Banerjee, Sube; Barber, Robert; Bentham, Peter; Brown, Richard G; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Johnson, Tony; Jones, Robert; Katona, Cornelius; Lindesay, James; Macharouthu, Ajay; McKeith, Ian; McShane, Rupert; O'Brien, John T; Phillips, Patrick P J; Sheehan, Bart; Howard, Robert

2017-12-01

Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease.

PubMed

Siano, Maria; De Gregorio, Fabiola; Boggia, Bartolo; Sepe, Angela; Ferri, Pasqualina; Buonpensiero, Paolo; Di Pasqua, Antonio; Raia, Valeria

2010-06-01

Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality. To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes. 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups. A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications. Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

PubMed Central

2014-01-01

Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial.

PubMed

Derks, Marloes G M; Blok, Erik J; Seynaeve, Caroline; Nortier, Johan W R; Kranenbarg, Elma Meershoek-Klein; Liefers, Gerrit-Jan; Putter, Hein; Kroep, Judith R; Rea, Daniel; Hasenburg, Annette; Markopoulos, Christos; Paridaens, Robert; Smeets, Jan B E; Dirix, Luc Y; van de Velde, Cornelis J H

2017-09-01

After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial. The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5-3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001. 6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0-10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65-69) for the exemestane group and 67% (65-69) for the sequential group (hazard ratio 0·96, 0·88-1·05; p=0·39). The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible. Pfizer, Dutch Cancer Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force

PubMed Central

Beiske, K; Burchill, S A; Cheung, I Y; Hiyama, E; Seeger, R C; Cohn, S L; Pearson, A D J; Matthay, K K

2009-01-01

Disseminating disease is a predictive and prognostic indicator of poor outcome in children with neuroblastoma. Its accurate and sensitive assessment can facilitate optimal treatment decisions. The International Neuroblastoma Risk Group (INRG) Task Force has defined standardised methods for the determination of minimal disease (MD) by immunocytology (IC) and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) using disialoganglioside GD2 and tyrosine hydroxylase mRNA respectively. The INRG standard operating procedures (SOPs) define methods for collecting, processing and evaluating bone marrow (BM), peripheral blood (PB) and peripheral blood stem cell harvest by IC and QRT-PCR. Sampling PB and BM is recommended at diagnosis, before and after myeloablative therapy and at the end of treatment. Peripheral blood stem cell products should be analysed at the time of harvest. Performing MD detection according to INRG SOPs will enable laboratories throughout the world to compare their results and thus facilitate quality-controlled multi-centre prospective trials to assess the clinical significance of MD and minimal residual disease in heterogeneous patient groups. PMID:19401690

Progestin treatment of atypical hyperplasia and well-differentiated adenocarcinoma of the endometrium to preserve fertility.

PubMed

Koskas, Martin; Azria, Elie; Walker, Francine; Luton, Dominique; Madelenat, Patrick; Yazbeck, Chadi

2012-03-01

To evaluate the outcome of a cohort of young women treated with progestin for fertility-sparing management of endometrial atypical hyperplasia (AH) and endometrial carcinoma (EC). This retrospective multicentre cohort study included women under the age of 40 years treated conservatively for AH and EC to preserve fertility using progestin for at least 3 months. Four inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists (including a reference pathologist); (ii) the use of conservative management for fertility sparing; (iii) adequate radiological examination before conservative management; and (iv) a minimal follow-up time of one year. Twenty-two patients fulfilled the inclusion criteria (8 had EC, and 14 had AH). After progestin treatment, 17 patients responded. Among the 17 patients who experienced remission, three also experienced disease relapse. One patient initially diagnosed with AH experienced progression of her disease to stage IIIA EC. Ten pregnancies were achieved in eight patients. Fertility-sparing management using progestin offers the opportunity to fulfil maternal desires in young patients diagnosed with AH and EC. However, progression of the disease is possible and close follow-up is needed.

ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes.

PubMed

Kenyon, S; Taylor, D J; Tarnow-Mordi, W O

2002-01-01

Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis. Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Comorbidities and the risk of mortality in patients with bronchiectasis: an international multicentre cohort study.

PubMed

McDonnell, Melissa J; Aliberti, Stefano; Goeminne, Pieter C; Restrepo, Marcos I; Finch, Simon; Pesci, Alberto; Dupont, Lieven J; Fardon, Thomas C; Wilson, Robert; Loebinger, Michael R; Skrbic, Dusan; Obradovic, Dusanka; De Soyza, Anthony; Ward, Chris; Laffey, John G; Rutherford, Robert M; Chalmers, James D

2016-12-01

Patients with bronchiectasis often have concurrent comorbidities, but the nature, prevalence, and impact of these comorbidities on disease severity and outcome are poorly understood. We aimed to investigate comorbidities in patients with bronchiectasis and establish their prognostic value on disease severity and mortality rate. An international multicentre cohort analysis of outpatients with bronchiectasis from four European centres followed up for 5 years was done for score derivation. Eligible patients were those with bronchiectasis confirmed by high-resolution CT and a compatible clinical history. Comorbidity diagnoses were based on standardised definitions and were obtained from full review of paper and electronic medical records, prescriptions, and investigator definitions. Weibull parametric survival analysis was used to model the prediction of the 5 year mortality rate to construct the Bronchiectasis Aetiology Comorbidity Index (BACI). We tested the BACI as a predictor of outcomes and explored whether the BACI added further prognostic information when used alongside the Bronchiectasis Severity Index (BSI). The BACI was validated in two independent international cohorts from the UK and Serbia. Between June 1, 2006, and Nov 22, 2013, 1340 patients with bronchiectasis were screened and 986 patients were analysed. Patients had a median of four comorbidities (IQR 2-6; range 0-20). 13 comorbidities independently predicting mortality rate were integrated into the BACI. The overall hazard ratio for death conferred by a one-point increase in the BACI was 1·18 (95% CI 1·14-1·23; p<0·0001). The BACI predicted 5 year mortality rate, hospital admissions, exacerbations, and health-related quality of life across all BSI risk strata (p<0·0001 for mortality and hospital admissions, p=0·03 for exacerbations, p=0·0008 for quality of life). When used in conjunction with the BSI, the combined model was superior to either model alone (p=0·01 for combined vs BACI; p=0·008 for combined vs BSI). Multimorbidity is frequent in bronchiectasis and can negatively affect survival. The BACI complements the BSI in the assessment and prediction of mortality and disease outcomes in patients with bronchiectasis. European Bronchiectasis Network (EMBARC). Copyright © 2016 Elsevier Ltd. All rights reserved.

[Comorbidity associated to overactive bladder syndrome].

PubMed

Castro Díaz, David; Rebollo, Pablo; González-Segura Alsina, Diego

2009-10-01

To estimate the percentage of patients with Overactive Bladder (OB) attending urology or gynaecology outpatient clinics who show associated diseases which complicate their clinical state and quality of life. This is an epidemiologic, cross-sectional and multicentre real world trial. 1,659 patients with OB were studied in urology or gynaecology outpatient clinics. Demographic data, anthropometric data, presence of chronic diseases (hypertension, diabetes, cerebrovascular disease, ischemic cardiopathy, chronic obstructive pulmonary disease, cognitive damaged, cataract, movement disability and constipation), presence of associated diseases (falls, lower urinary tract infections, genital skin infections, depression, sexual dysfunction and sleep disorders), presence of urinary incontinence symptoms and impact on quality of life according to ICIQ-UI SF score. Mean age (S.D) of studied sample was 59.2 (12.9) years and 73.6% were female. Most patients lived in urban settings (67.3%), had primary studies or less (56.8%) and had active work or at home work (66.2%). Most frequent diseases associated to OB were genital skin infections, lower urinary tract infections and sleep disorders. Sexual dysfunction was more frequent in males than in females; lower urinary tract infections, genital skin infections and depression were more frequent in females than in males. Patients with these diseases showed higher ICIQ-UI SF scores than patients without them, indicating higher impact. Presence of associated diseases in patients with OB is frequent in males and females and it is associated to higher impact in patient's life. It seems relevant to pay attention in detecting them through the medical history of patients consulting about OB or urinary incontinence symptoms.

Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)

PubMed Central

Adrion, Christine; Fischer, Carolin Simone; Wagner, Judith; Gürkov, Robert; Mansmann, Ulrich

2016-01-01

Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms. What this study adds Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere’s disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere’s disease. Funding, competing interests, data sharing Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668. PMID:26797774

The CNDR: collaborating to translate new therapies for Canadians.

PubMed

Korngut, Lawrence; Campbell, Craig; Johnston, Megan; Benstead, Timothy; Genge, Angela; Mackenzie, Alex; McCormick, Anna; Biggar, Douglas; Bourque, Pierre; Briemberg, Hannah; O'Connell, Colleen; Dojeiji, Suzan; Dooley, Joseph; Grant, Ian; Hogan, Gillian; Johnston, Wendy; Kalra, Sanjay; Katzberg, Hans D; Mah, Jean K; McAdam, Laura; McMillan, Hugh J; Melanson, Michel; Selby, Kathryn; Shoesmith, Christen; Smith, Garth; Venance, Shannon L; Wee, Joy

2013-09-01

Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

Motivation is a crucial factor for adherence to a healthy lifestyle among people with coronary heart disease after percutaneous coronary intervention.

PubMed

Kähkönen, Outi; Kankkunen, Päivi; Saaranen, Terhi; Miettinen, Heikki; Kyngäs, Helvi; Lamidi, Marja-Leena

2015-10-01

To test the Theory of Adherence of People with Chronic Disease with regard to adherence to treatment among patients with coronary heart disease after a percutaneous coronary intervention. Increased knowledge of the concept of adherence is needed for the development of nursing interventions and nursing guidelines for patients with coronary heart disease. A cross-sectional, multi-centre study. This study was conducted from February-December 2013 with 416 patients with coronary heart disease 4 months after undergoing a percutaneous coronary intervention. A self-reported questionnaire was used to assess their adherence to treatment. Data were analysed using structural equation modelling. The theory explained 45% of the adherence to a healthy lifestyle and 7% of the adherence to medication. Structural equation modelling confirmed that motivation and results of care had the highest association with adherence to a healthy lifestyle. Responsibility was associated with adherence to medication. Support from next of kin, support from nurses and physicians, and motivation, co-operation, fear of complications and a sense of normality were associated with adherence. Patients who are motivated to perform self-care and consider the results of care to be important were more likely to adhere to a healthy lifestyle. Responsible patients were more likely to adhere to their medication. It is important to account for these elements as a part of secondary prevention strategies among patients with coronary heart disease after a percutaneous coronary intervention. © 2015 John Wiley & Sons Ltd.

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

PubMed Central

Gross, V; Andus, T; Ecker, K; Raedler, A; Loeschke, K; Plauth, M; Rasenack, J; Weber, A; Gierend, M; Ewe, K; Scholmerich, J; Budesonide, S

1998-01-01

Background—The relapse rate after steroid induced remission in Crohn's disease is high. 
Aims—To test whether oral pH modified release budesonide (3 × 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. 
Methods—In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 × 1 mg budesonide (n=84) or placebo (n=95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. 
Results—Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. 
Conclusion—Oral pH modified release budesonide at a dose of 3 × 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease. 

 Keywords: budesonide; Crohn's disease; maintenance of remission PMID:9616309

Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics

PubMed Central

Turnbull, Pauline; Hawton, Keith; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Townsend, Ellen; Khundakar, Kazem; Kapur, Nav

2016-01-01

Objective Rates of hospital presentation for self-harm in England were compared using different national and local data sources. Design The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. Setting Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). Primary outcome Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. Results The total number of self-harm episodes between 2010 and 2012 was 13 547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. Conclusions There was a consistent underestimation of presentations for self-harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self-harm. PMID:26883238

The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre, observational, retrospective, post-marketing study.

PubMed

Valldeoriola, Francesc; Salvador, Antonio; Gómez-Arguelles, José Maria; Marey, José; Moya, Miguel; Ayuga, Ángel; Ramírez, Francisco

2018-04-01

This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: -1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: -2.6 ± 8.0; p < 0.0001). In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

PubMed Central

2010-01-01

Background For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. Methods The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Results Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. Conclusions For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review. PMID:20673343

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

PubMed

Timmermann, Lars; Jain, Roshini; Chen, Lilly; Maarouf, Mohamed; Barbe, Michael T; Allert, Niels; Brücke, Thomas; Kaiser, Iris; Beirer, Sebastian; Sejio, Fernando; Suarez, Esther; Lozano, Beatriz; Haegelen, Claire; Vérin, Marc; Porta, Mauro; Servello, Domenico; Gill, Steven; Whone, Alan; Van Dyck, Nic; Alesch, Francois

2015-07-01

High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study. The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinson's disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects. Boston Scientific. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial.

PubMed

Migden, Michael R; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kudchadkar, Ragini; Trefzer, Uwe; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Chang, Anne Lynn S; Cornélis, Frank; Lear, John T; Sellami, Dalila; Dummer, Reinhard

2015-06-01

Patients with advanced basal cell carcinoma have limited treatment options. Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma. BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. Patients were randomised via an automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily, stratified by disease, histological subtype, and geographical region. The primary endpoint was the proportion of patients who achieved an objective response, assessed in the primary efficacy analysis population (patients with fully assessable locally advanced disease and all those with metastatic disease) with data collected up to 6 months after randomisation of the last patient. This trial is registered with ClinicalTrials.gov, number NCT01327053. Between July 20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib group, and 151 in the 800 mg sonidegib group. Median follow-up was 13·9 months (IQR 10·1-17·3). In the primary efficacy analysis population, 20 (36%, 95% CI 24-50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116 receiving 800 mg sonidegib achieved an objective response. In the 200 mg sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective response, as assessed by central review, were noted among the 42 with locally advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally advanced disease had an objective response, as assessed by central review, as did four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200 mg group than in the 800 mg group. The most common grade 3-4 adverse events were raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group. The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat. Novartis Pharmaceuticals Corporation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study.

PubMed

Martín-Richard, Marta; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Angel; Quindós, Maria; Maisonobe, Pascal

2013-09-20

Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

Septic arthritis in haemodialysis patients: a seven-year multi-centre review.

PubMed

Al-Nammari, S S; Gulati, V; Patel, R; Bejjanki, N; Wright, M

2008-04-01

To determine relevant demographics, clinical features, and outcomes for septic arthritis in patients on haemodialysis for end-stage renal failure. A multi-centre retrospective review was performed from 1999 to 2005. 15 cases were identified. The mean age of the patients at diagnosis was 67 (range, 23-89) years and 11 were male. All had multiple co-morbidities and additional risk factors for sepsis. The primary sources of sepsis were dialysis access-related (n=12), unknown in 2, and unrelated soft tissue infection in one. All patients presented with acute monoarticular symptoms; the knee joint was affected in 11 patients. The white cell count, neutrophil count, and C-reactive protein concentration were elevated in 10, 10, and 15 patients, respectively. All patients had positive synovial fluid cultures and blood cultures were positive in 14. Organisms isolated were all skin commensals, being staphylococcal in 13 and streptococcal in 2. Six patients had concomitant rheumatological disease (gout in 4, pseudogout in one, and rheumatoid arthritis in one). Two had urate crystals in the synovial fluid (noted by microscopy). All patients underwent antimicrobial therapy for a mean of 36 days, together with joint washouts and debridement. 12 patients were cured of infection; 2 developed chronic sepsis secondary to localised osteomyelitis; and one died of sepsis. Septic arthritis is a potentially devastating condition. Early and aggressive joint lavage and debridement combined with appropriate antimicrobial therapy is imperative. A high index of suspicion is necessary in haemodialysis patients; the diagnosis of septic arthritis must be presumed until proven otherwise.

Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study.

PubMed

Cho, Iksung; Al'Aref, Subhi J; Berger, Adam; Ó Hartaigh, Bríain; Gransar, Heidi; Valenti, Valentina; Lin, Fay Y; Achenbach, Stephan; Berman, Daniel S; Budoff, Matthew J; Callister, Tracy Q; Al-Mallah, Mouaz H; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Villines, Todd C; Hadamitzky, Martin; Hausleiter, Joerg; Leipsic, Jonathon; Shaw, Leslee J; Kaufmann, Philipp A; Feuchtner, Gudrun; Kim, Yong-Jin; Maffei, Erica; Raff, Gilbert; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Chang, Hyuk-Jae; Min, James K

2018-03-14

The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all). Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis following a multicentre randomised controlled trial.

PubMed

Vullings, Rik; Verdurmen, Kim M J; Hulsenboom, Alexandra D J; Scheffer, Stephanie; de Lau, Hinke; Kwee, Anneke; Wijn, Pieter F F; Amer-Wåhlin, Isis; van Laar, Judith O E H; Oei, S Guid

2017-01-01

Reducing perinatal morbidity and mortality is one of the major challenges in modern health care. Analysing the ST segment of the fetal electrocardiogram was thought to be the breakthrough in fetal monitoring during labour. However, its implementation in clinical practice yields many false alarms and ST monitoring is highly dependent on cardiotocogram assessment, limiting its value for the prediction of fetal distress during labour. This study aims to evaluate the relation between physiological variations in the orientation of the fetal electrical heart axis and the occurrence of ST events. A post-hoc analysis was performed following a multicentre randomised controlled trial, including 1097 patients from two participating centres. All women were monitored with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal quality, missing blood gas analysis, and congenital heart disease were excluded. The orientation of the fetal electrical heart axis affects the height of the initial T/QRS baseline, and therefore the incidence of ST events. We grouped tracings with the same initial baseline T/QRS value. We depicted the number of ST events as a function of the initial baseline T/QRS value with a linear regression model. A significant increment of ST events was observed with increasing height of the initial T/QRS baseline, irrespective of the fetal condition; correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12. The orientation of the fetal electrical heart axis and accordingly the height of the initial T/QRS baseline should be taken into account in fetal monitoring with ST analysis.

Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

PubMed

Jiang, Xiao-Han; Wang, Si-Bo; Tian, Qian; Zhong, Chi; Zhang, Guan-Ling; Li, Ya-Jie; Lin, Pan; You, Yong; Guo, Rong; Cui, Ying-Hua; Xing, Ying-Qi

2018-02-14

Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. No. NCT02425696 ; registered on April 21, 2015.

Validation of standard operating procedures in a multicenter retrospective study to identify -omics biomarkers for chronic low back pain.

PubMed

Dagostino, Concetta; De Gregori, Manuela; Gieger, Christian; Manz, Judith; Gudelj, Ivan; Lauc, Gordan; Divizia, Laura; Wang, Wei; Sim, Moira; Pemberton, Iain K; MacDougall, Jane; Williams, Frances; Van Zundert, Jan; Primorac, Dragan; Aulchenko, Yurii; Kapural, Leonardo; Allegri, Massimo

2017-01-01

Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs) for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres) retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1) blood collection, (2) sample processing and storage, (3) shipping details and (4) cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

Optimisation and validation of a remote monitoring system (Onco-TreC) for home-based management of oral anticancer therapies: an Italian multicentre feasibility study

PubMed Central

Passardi, Alessandro; Rizzo, Mimma; Maines, Francesca; Tondini, Carlo; Zambelli, Alberto; Vespignani, Roberto; Andreis, Daniele; Massa, Ilaria; Dianti, Marco; Forti, Stefano; Piras, Enrico Maria; Eccher, Claudio

2017-01-01

Introduction Despite the growing number of oral agents available for cancer treatment, their efficacy may be reduced due to the lack of adherence, inappropriate adverse event self-management and arbitrary dose adjustment. The management of anticancer therapies could exponentially benefit from the introduction of mobile health technologies in a highly integrated electronic oncology system. Methods and analysis We plan to customise and fine-tune an existing monitoring TreC platform used in different chronic diseases in the oncology setting. This project follows a multistep approach with two major purposes: 1. participatory design techniques driven by Health Literacy and Patient Reported Outcomes principles in order to adapt the system to the oncology setting involving patients and healthcare providers; 2. a prospective training-validation, interventional, non-pharmacological, multicentre study on a series of consecutive patients with cancer (20 and 60 patients in the training and validation steps, respectively) in order to assess system capability, usability and acceptability. The novel Onco-TreC 2.0 is expected to contribute to improving the adherence and safety of cancer care, promoting patient empowerment and patient–doctor communication. Ethics and dissemination Ethical approval was obtained from the Independent Ethics Committees of the participating institutions (CEIIAV protocol Number 2549/2015; reference Number 1315-PU). Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. Trial registration number ClinicalTrials.gov (NCT02921724); (Pre-results). Other study ID Number: IRST100.18. PMID:28554917

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

PubMed Central

2013-01-01

Background Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. Methods This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Results Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. Trial registration ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18. PMID:24053191

Network for Surveillance of Severe Maternal Morbidity: a powerful national collaboration generating data on maternal health outcomes and care.

PubMed

Cecatti, J G; Costa, M L; Haddad, S M; Parpinelli, M A; Souza, J P; Sousa, M H; Surita, F G; Pinto E Silva, J L; Pacagnella, R C; Passini, R

2016-05-01

To identify cases of severe maternal morbidity (SMM) during pregnancy and childbirth, their characteristics, and to test the feasibility of scaling up World Health Organization criteria for identifying women at risk of a worse outcome. Multicentre cross-sectional study. Twenty-seven referral maternity hospitals from all regions of Brazil. Cases of SMM identified among 82 388 delivering women over a 1-year period. Prospective surveillance using the World Health Organization's criteria for potentially life-threatening conditions (PLTC) and maternal near-miss (MNM) identified and assessed cases with severe morbidity or death. Indicators of maternal morbidity and mortality; sociodemographic, clinical and obstetric characteristics; gestational and perinatal outcomes; main causes of morbidity and delays in care. Among 9555 cases of SMM, there were 140 deaths and 770 cases of MNM. The main determining cause of maternal complication was hypertensive disease. Criteria for MNM conditions were more frequent as the severity of the outcome increased, all combined in over 75% of maternal deaths. This study identified around 9.5% of MNM or death among all cases developing any severe maternal complication. Multicentre studies on surveillance of SMM, with organised collaboration and adequate study protocols can be successfully implemented, even in low-income and middle-income settings, generating important information on maternal health and care to be used to implement appropriate health policies and interventions. Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil. © 2015 Royal College of Obstetricians and Gynaecologists.

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

PubMed

Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

2018-06-01

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

European Network of Bipolar Research Expert Centre (ENBREC): a network to foster research and promote innovative care.

PubMed

Henry, Chantal; Andreassen, Ole A; Barbato, Angelo; Demotes-Mainard, Jacques; Goodwin, Guy; Leboyer, Marion; Vieta, Eduard; Nolen, Willem A; Kessing, Lars Vedel; Scott, Jan; Bauer, Michael

2013-01-01

Bipolar disorders rank as one of the most disabling illnesses in working age adults worldwide. Despite this, the quality of care offered to patients with this disorder is suboptimal, largely due to limitations in our understanding of the pathology. Improving this scenario requires the development of a critical mass of expertise and multicentre collaborative projects. Within the framework of the European FP7 programme, we developed a European Network of Bipolar Research Expert Centres (ENBREC) designed specifically to facilitate EU-wide studies. ENBREC provides an integrated support structure facilitating research on disease mechanisms and clinical outcomes across six European countries (France, Germany, Italy, Norway, Spain and the UK). The centres are adopting a standardised clinical assessment that explores multiple aspects of bipolar disorder through a structured evaluation designed to inform clinical decision-making as well as being applicable to research. Reliable, established measures have been prioritised, and instruments have been translated and validated when necessary. An electronic healthcare record and monitoring system (e-ENBREC©) has been developed to collate the data. Protocols to conduct multicentre clinical observational studies and joint studies on cognitive function, biomarkers, genetics, and neuroimaging are in progress; a pilot study has been completed on strategies for routine implementation of psycho-education. The network demonstrates 'proof of principle' that expert centres across Europe can collaborate on a wide range of basic science and clinical programmes using shared protocols. This paper is to describe the network and how it aims to improve the quality and effectiveness of research in a neglected priority area.

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).

PubMed

Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

2008-09-01

Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs.

Retinitis pigmentosa in Spain. The Spanish Multicentric and Multidisciplinary Group for Research into Retinitis Pigmentosa.

PubMed

Ayuso, C; Garcia-Sandoval, B; Najera, C; Valverde, D; Carballo, M; Antiñolo, G

1995-09-01

Retinitis pigmentosa is a term commonly given to a group of inherited and progressive disorders which affect the photoreceptors of the retina. As part of an ongoing research programme throughout Spain, clinical, epidemiological, and genetic studies have been carried out on these diseases. Here, we report the relative frequencies of the different genetic types in 503 non-syndromic and 89 syndromic RP families of Spanish origin. The most frequent syndromic RP forms were Usher syndrome type 1 (20/89 families = 30%) and Usher syndrome type 2 (44 families = 49%). Among non-syndromic RP forms, 12% were autosomal dominant, 39% autosomal recessive and 4% X-linked. Forty-one percent were isolated or simplex cases and in 4% the genetic type could not be established.

JUVENILE SCLERODERMA-what has changed in the meantime?

PubMed

Adrovic, Amra; Sahin, Sezgin; Barut, Kenan; Kasapcopur, Ozgur

2018-04-22

Juvenile scleroderma is a rarely seen chronic connective tissue disorder characterized by stiffening of the skin. The frequency of the disease was reported as one per million. According to organ involvement, the disease is divided into two main forms: systemic and localized scleroderma. Since it is uncommon in children, many aspects of the disease remain discussable. With this review, we aimed to revise recent findings and new developments in this rare condition. Skin manifestations are most prominent feature of the systemic form, followed by musculoskeletal and vascular involvement. Cardiovascular, gastrointestinal and renal disorders are rare in childhood. Combination of disease modifying antirheumatic drugs (methotrexate, mycophenolate-mofetil, cyclosporine) and steroid reprents the first line therapy. Bosentan is used for cases with pulmonary hypertension and for extensive digital ulcerations. Biological treatment emerges as a useful treatment option in most severe form of the disease. Localized scleroderma is characterized with sclerodermatosis of the skin. Internal organ involvement is not expected. Classification of the local scleroderma is made according to the size and localization of the skin changes. There are few different therapeutical options but there is no specific therapy for the localized scleroderma. Many data regarding disease features and treatment options in juvenile scleroderma are based on studies among adults. There is a striking need for multicentric, prospective studies among children with juvenile scleroderma.Emerging biological agents and new treatment options are showing promising results. Anyhow, juvenile scleroderma remains a mystery with many aspects of the disease waiting to be solved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

PubMed

Mukherjee, Partha S; Vishnubhatla, Sreenivas; Amarapurkar, Deepak N; Das, Kausik; Sood, Ajit; Chawla, Yogesh K; Eapen, Chundamannil E; Boddu, Prabhakar; Thomas, Varghese; Varshney, Subodh; Hidangmayum, Diamond Sharma; Bhaumik, Pradip; Thakur, Bhaskar; Acharya, Subrat K; Chowdhury, Abhijit

2017-01-01

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

QUEST‐RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries

PubMed Central

Sokka, Tuulikki; Kautiainen, Hannu; Toloza, Sergio; Mäkinen, Heidi; Verstappen, Suzan M M; Hetland, Merete Lund; Naranjo, Antonio; Baecklund, Eva; Herborn, Gertraud; Rau, Rolf; Cazzato, Massimiliano; Gossec, Laure; Skakic, Vlado; Gogus, Feride; Sierakowski, Stanislaw; Bresnihan, Barry; Taylor, Peter; McClinton, Catherine; Pincus, Theodore

2007-01-01

Objective To conduct a cross‐sectional review of non‐selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. Methods The review included current disease activity using data from clinical assessment and a patient self‐report questionnaire, which was translated into each language. Data on demographic, disease and treatment‐related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28‐joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. Results Between January 2005 and October 2006, the QUEST‐RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 ⩽3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. Conclusions This international multicentre cross‐sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005–6 including countries that are infrequently involved in clinical research projects. PMID:17412740

A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

PubMed

Rigg, J R A

2016-07-01

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies

PubMed Central

Kawashima, Shoji; Kato, Takashi

2012-01-01

Background Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. Objectives The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. Design Prospective cohort study. Setting and participants SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose–positron emission tomography (FDG-PET) were enrolled from the USA. Methods Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. Results SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. Conclusions Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients. PMID:22535791

Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix™).

PubMed

Croxtall, Jamie D; Dhillon, Sohita

2012-12-24

Nimenrix™ (MenACWY-TT) is a quadrivalent meningococcal conjugate vaccine, comprising the polysaccharide serogroups A, C, W135 and Y, and tetanus toxoid (TT) as carrier protein. It is the first quadrivalent vaccine (administered as a single dose) to be approved in Europe for active immunization of individuals aged ≥ 12 months against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W135 and Y. Administration of a single dose of Nimenrix™ elicited a strong immune response against all four vaccine serogroups in healthy toddlers aged 12-23 months, children and adolescents aged 2-17 years and adults aged 18-55 years in randomized, multicentre, phase III trials. In toddlers, Nimenrix™ was noninferior to Meningitec® in terms of seroresponse rates against meningococcal serogroup C 42 days post-vaccination. In children, adolescents and adults, Nimenrix™ was noninferior to Mencevax™ in terms of vaccination response rates against all four serogroups 1 month post-vaccination. Furthermore, several phase II studies and a phase III trial showed that the immune response elicited by Nimenrix™ in all age groups persisted for 7-42 months after the primary vaccination (when evaluated by rabbit serum bactericidal activity), with the vaccine also inducing immune memory in toddlers. In addition, several randomized, multicentre, phase III, noninferiority trials showed that when coadministered with other childhood vaccines or a seasonal flu vaccine, the immunogenicity of Nimenrix™ or that of the coadministered vaccine was generally not altered. Nimenrix® was generally well tolerated in all age groups whether administered as a single vaccine or coadministered with other routine vaccines. The incidence of grade 3 local or systemic solicited adverse events during the first 4 days following vaccination and of serious adverse events over an extended follow-up period of up to 6 months was low (<4.5%). Although protective effectiveness and longer-term persistence studies are required, current evidence suggests that Nimenrix™, administered as a single dose, provides a valuable vaccination option for the prevention of meningococcal disease across a broad age group, including children as young as 12 months.

Prevalence of adherence to treatment in homebound elderly people in primary health care: a descriptive, cross-sectional, multicentre study.

PubMed

Cárdenas-Valladolid, Juan; Martín-Madrazo, Carmen; Salinero-Fort, Miguel A; Carrillo de-Santa Pau, Enrique; Abánades-Herranz, Juan C; de Burgos-Lunar, Carmen

2010-08-01

Adherence to the therapeutic plan is one of the most important health issues in terms of treatment efficacy, healthcare costs and patient safety. Unfortunately, homebound elderly patients are especially vulnerable to nonadherence because they have higher morbidity rates combined with cognitive and social problems that hinder their correct use of drugs. The level of therapeutic adherence in homebound elderly people has not been adequately studied. To estimate the prevalence of therapeutic adherence, using the Morisky-Green test, in homebound elderly patients taking polypharmacy (defined as use of four or more drugs), and to study the factors associated with adherence. This was a descriptive, cross-sectional, multicentre study. A total of 327 patients were selected by random start systematic sampling from the total number of homebound patients taking four or more drugs in Healthcare Area 4 of the Madrid Autonomous Region, Spain. Through an in-home survey of patients and their caregivers, information was gathered on sociodemographic data, co-morbidities, number of hospital admissions, responsibility for purchasing and preparation of the medication, level of cognitive impairment (Pfeiffer questionnaire), functional dependence in activities of daily living (Katz Index), knowledge of the disease (Batalla test), adherence to treatment (Morisky-Green test), visual and auditory perception, and caregiver burden (Zarit interview). Of the homebound patients, 65.7% (95% CI 60.6, 70.9) had good adherence to treatment. The variables most negatively associated with therapeutic adherence, after adjustment for age, sex, number of drugs, knowledge of the disease, and cognitive function, were a large caregiver burden (odds ratio [OR] 3.09; 95% CI 1.75, 5.48) and impaired hearing (OR 2.00; 95% CI 1.17, 3.40). There was also a trend toward a positive association between nonadherence and patients aged <85 years (OR 1.57; 95% CI 0.93, 2.65) and patients who had nine or more drug prescriptions (OR 1.59; 95% CI 0.96, 2.65). Poor therapeutic adherence in homebound elderly patients receiving polypharmacy is a serious problem affecting one of every three individuals concerned, and is directly related to caregiver burden, regardless of age, sex, cognitive status or number of drugs administered.

Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and children with Gaucher disease.

PubMed

Zimran, Ari; Wajnrajch, Michael; Hernandez, Betina; Pastores, Gregory M

2018-02-23

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the findings across six key taliglucerase alfa clinical studies. A total of 33 treatment-naïve adult patients were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose-comparison pivotal study, after which eligible patients continued into two consecutive extension studies; 17 treatment-naïve adult patients completed 5 total years of treatment with taliglucerase alfa. In the only ERT study focused on exclusively paediatric patients with GD, 11 treatment-naïve children were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre, double-blind study; nine completed 3 total years of treatment in a dedicated paediatric extension study. The effect of switching patients from imiglucerase to taliglucerase alfa was also investigated in a separate 9-month study that included 26 adults and five children; 10 adults completed a total of 3 years and two children completed a total of 2.75 years of taliglucerase alfa treatment in the extension studies. All studies evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy. Detailed results from baseline through the end of these studies are presented. Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naïve patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters. Together, this comprehensive data set supports the treatment of adult and paediatric patients with GD who are naïve to ERT or who have previously been treated with imiglucerase.

Ethical issues: the multi-centre low-risk ethics/governance review process and AMOSS.

PubMed

Vaughan, Geraldine; Pollock, Wendy; Peek, Michael J; Knight, Marian; Ellwood, David; Homer, Caroline S; Pulver, Lisa Jackson; McLintock, Claire; Ho, Maria T; Sullivan, Elizabeth A

2012-04-01

The Australasian Maternity Outcomes Surveillance System (AMOSS) conducts surveillance and research of rare and serious conditions in pregnancy. This multi-centre population health study is considered low risk with minimal ethical impact. To describe the ethics/governance review pathway undertaken by AMOSS. Prospective, descriptive study during 2009-2011 of the governance/ethical review processes required to gain approval for Australian and New Zealand (ANZ) maternity units with more than 50 births per year (n = 303) to participate in AMOSS. Review processes ranged from a single application for 24 NZ sites, a single application for eligible hospitals in two Australian states, full Health Research Ethics Committee (HREC) applications for individual hospitals, through simple letters of support. As of September 2011, 46 full/expedited ethics applications, 131 site governance applications and 136 letters of support requests were made over 33 months, involving an estimated 3261 hours by AMOSS staff/investigators, and an associated resource burden by participating sites, to obtain approval to receive nonidentifiable data from 291 hospitals. The AMOSS research system provides an important resource to enhance knowledge of conditions that cause rare and serious maternal morbidity. Yet the highly variable ethical approval processes required to implement this study have been excessively repetitive and burdensome. This process jeopardises timely, efficient research project implementation, without corresponding benefits to research participants. The resource burden to establish research governance for AMOSS confirms the urgent need for the Harmonisation of Multi-centre Ethical Review (HoMER) to further streamline ethics/governance review processes for multi-centre research. © 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

Multicentre investigation of pathogenic bacteria and antibiotic resistance genes in Chinese patients with acute exacerbation of chronic obstructive pulmonary disease.

PubMed

Ma, Xiuqing; Cui, Junchang; Wang, Jing; Chang, Yan; Fang, Qiuhong; Bai, Changqing; Zhou, Xiumei; Zhou, Hong; Feng, Huasong; Wang, Ying; Zhao, Weiguo; Wen, Zhongguang; Wang, Ping; Liu, Yi; Yu, Ling; Li, Chunsun; Chen, Liangan

2015-10-01

A prospective observational study to investigate the distribution and antimicrobial resistance of pathogenic bacteria in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing, China. Patients with AECOPD were recruited from 11 general hospitals. Sputum specimens were cultured and bacteria identified. Antibiotic susceptibility was determined for each isolate, and presence of antibiotic resistance genes was evaluated using polymerase chain reaction. Pathogenic bacteria were isolated from 109/318 patients (34.28%); 124 isolates of 22 pathogenic bacterial species were identified, including Klebsiella pneumoniae (16.94%), Pseudomonas aeruginosa (16.94%), Acinetobacter baumannii (11.29%), Streptococcus pneumoniae (8.87%), and Staphylococcus aureus (7.26%). S. aureus was sensitive to tigecycline, teicoplanin, vancomycin and linezolid but resistant to penicillin and levofloxacin. K.pneumoniae, P. aeruginosa, A. baumannii and E. coli were susceptible to amikacin and cefoperazone. K. pneumoniae and P. aeruginosa are the most common pathogenic bacteria in AECOPD cases in Beijing, China. Our antibiotic resistance findings may be helpful in selecting antibiotic therapy. © The Author(s) 2015.

Risk of infectious mononucleosis among agonistic swimmers: a cross-sectional study.

PubMed

Gallone, M S; Astuto, L; Mastrorilli, G; Tamma, R; Ascatigno, L; Sinesi, D; Notarnicola, A; Tafuri, S

2016-01-01

The risk of infectious mononucleosis among athletes is quite debated. Some personal observations seem to suggest an increase risk of mononucleosis among athletes, because they attend always close settings with an high probability of respiratory pathogens transmission; overtraining has been also proposed as risk factor. Cross-sectional study in a group of swimmers (aged 11-14 years) of the University Sport Centre of Bari. 40 swimmers were interviewed by healthcare personnel at the end of training courses; demographic characteristics, personal habits, information about sport training and diagnosis of mononucleosis were analysed. The life-time incidence of mononucleosis was around 40%; multivariate analysis showed the association between mononucleosis and use of bottles of other persons (aOR=8.2; 95% CI=1.4-49.2; z=2.32; p=0.021) and average duration of training session was longer among subjects who reported mononucleosis than in subjects who did not indicate this disease. Future multi-centric studies are needed to better define the epidemiology of the mononucleosis in sport settings and to formulate appropriate recommendations to prevent the spreading of this disease.

Delineation of the motor disorder of Lesch–Nyhan disease

PubMed Central

Jinnah, H. A.; Visser, Jasper E.; Harris, James C.; Verdu, Alfonso; Larovere, Laura; Ceballos-Picot, Irene; Gonzalez-Alegre, Pedro; Neychev, Vladimir; Torres, Rosa J.; Dulac, Olivier; Desguerre, Isabelle; Schretlen, David J.; Robey, Kenneth L.; Barabas, Gabor; Bloem, Bastiaan R.; Nyhan, William; De Kremer, Raquel; Eddey, Gary E.; Puig, Juan G.; Reich, Stephen G.

2012-01-01

Lesch–Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia. PMID:16549399

Epoch-based Entropy for Early Screening of Alzheimer's Disease.

PubMed

Houmani, N; Dreyfus, G; Vialatte, F B

2015-12-01

In this paper, we introduce a novel entropy measure, termed epoch-based entropy. This measure quantifies disorder of EEG signals both at the time level and spatial level, using local density estimation by a Hidden Markov Model on inter-channel stationary epochs. The investigation is led on a multi-centric EEG database recorded from patients at an early stage of Alzheimer's disease (AD) and age-matched healthy subjects. We investigate the classification performances of this method, its robustness to noise, and its sensitivity to sampling frequency and to variations of hyperparameters. The measure is compared to two alternative complexity measures, Shannon's entropy and correlation dimension. The classification accuracies for the discrimination of AD patients from healthy subjects were estimated using a linear classifier designed on a development dataset, and subsequently tested on an independent test set. Epoch-based entropy reached a classification accuracy of 83% on the test dataset (specificity = 83.3%, sensitivity = 82.3%), outperforming the two other complexity measures. Furthermore, it was shown to be more stable to hyperparameter variations, and less sensitive to noise and sampling frequency disturbances than the other two complexity measures.

Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial

PubMed Central

Spackman, Eldon; Sculpher, Mark; Howard, Jo; Malfroy, Moira; Llewelyn, Charlotte; Choo, Louise; Hodge, Renate; Johnson, Tony; Rees, David C; Fijnvandraat, Karin; Kirby-Allen, Melanie; Davies, Sally; Williamson, Lorna

2014-01-01

The study’s objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß0thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the ‘within-trial’ analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from −£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY. PMID:24329965

A multicentre observational study for early diagnosis of Gaucher disease in patients with Splenomegaly and/or Thrombocytopenia.

PubMed

Motta, Irene; Filocamo, Mirella; Poggiali, Erika; Stroppiano, Marina; Dragani, Alfredo; Consonni, Dario; Barcellini, Wilma; Gaidano, Gianluca; Facchini, Luca; Specchia, Giorgina; Cappellini, Maria Domenica

2016-04-01

Gaucher disease (GD) is the most common lysosomal disorder resulting from deficient activity of the β-glucosidase enzyme that causes accumulation of glucosylceramide in the macrophage-monocyte system. Notably, because of non-specific symptoms and a lack of awareness, patients with GD experience long diagnostic delays. The aim of this study was to apply a diagnostic algorithm to identify GD type 1 among adults subjects referred to Italian haematology outpatient units because of splenomegaly and/or thrombocytopenia and, eventually, to estimate the prevalence of GD in this selected population. One hundred and ninety-six subjects (61 females, 135 males; mean age 47.8 ± 18.2 years) have been enrolled in the study and tested for β-glucosidase enzyme activity on dried blood spot (DBS). Seven of 196 patients have been diagnosed with GD, (5 females and 2 males) with mean age 31.8 ± 8.2 years, with a prevalence of 3.6% (with a prevalence of 3.6% (I95% CI 1.4-7.2; 1/28 patients) in this population. These results show that the use of an appropriate diagnostic algorithm and a simple diagnostic method, such as DBS, are important tools to facilitate the diagnosis of a rare disease even for not disease-expert physicians. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emerging preclinical pharmacological targets for Parkinson's disease

PubMed Central

More, Sandeep Vasant; Choi, Dong-Kug

2016-01-01

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms. PMID:26988916

T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

PubMed

Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry.

PubMed

Bonnot, Olivier; Gama, Clarissa S; Mengel, Eugen; Pineda, Mercè; Vanier, Marie T; Watson, Louise; Watissée, Marie; Schwierin, Barbara; Patterson, Marc C

2017-10-09

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease that should be recognised by psychiatrists as a possible underlying cause of psychiatric abnormalities. This study describes NP-C patients who had psychiatric manifestations at enrolment in the international NPC Registry, a unique multicentre, prospective, observational disease registry. Treating physicians' data entries describing psychiatric manifestations in NPC patients were coded and grouped by expert psychiatrists. Out of 386 NP-C patients included in the registry as of October 2015, psychiatric abnormalities were reported to be present in 34% (94/280) of those with available data. Forty-four patients were confirmed to have identifiable psychiatric manifestations, with text describing these psychiatric manifestations. In these 44 patients, the median (range) age at onset of psychiatric manifestations was 17.9 years (2.5-67.9; n = 15), while the median (range) age at NP-C diagnosis was 23.7 years (0.2-69.8; n = 34). Almost all patients (43/44; 98%) had an occurrence of ≥1 neurological manifestation at enrolment. These data show that substantial delays in diagnosis of NP-C are long among patients with psychiatric symptoms and, moreover, patients presenting with psychiatric features and at least one of cognitive impairment, neurological manifestations, and/or visceral symptoms should be screened for NP-C.

Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy.

PubMed

Probst, Pascal; Hüttner, Felix J; Klaiber, Ulla; Knebel, Phillip; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2015-11-06

Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment.

PubMed

Vogel, Adam P; Rommel, Natalie; Sauer, Carina; Horger, Marius; Krumm, Patrick; Himmelbach, Marc; Synofzik, Matthis

2017-06-01

Screening assessments for dysphagia are essential in neurodegenerative disease. Yet there are no purpose-built tools to quantify swallowing deficits at bedside or in clinical trials. A quantifiable, brief, easy to administer assessment that measures the impact of dysphagia and predicts the presence or absence of aspiration is needed. The Clinical Assessment of Dysphagia in Neurodegeneration (CADN) was designed by a multidisciplinary team (neurology, neuropsychology, speech pathology) validated against strict methodological criteria in two neurodegenerative diseases, Parkinson's disease (PD) and degenerative ataxia (DA). CADN comprises two parts, an anamnesis (part one) and consumption (part two). Two-thirds of patients were assessed using reference tests, the SWAL-QOL symptoms subscale (part one) and videofluoroscopic assessment of swallowing (part two). CADN has 11 items and can be administered and scored in an average of 7 min. Test-retest reliability was established using correlation and Bland-Altman plots. 125 patients with a neurodegenerative disease were recruited; 60 PD and 65 DA. Validity was established using ROC graphs and correlations. CADN has sensitivity of 79 and 84% and specificity 71 and 69% for parts one and two, respectively. Significant correlations with disease severity were also observed (p < 0.001) for PD with small to large associations between disease severity and CADN scores for DA. Cutoff scores were identified that signal the presence of clinically meaningful dysphagia symptomatology and risk of aspiration. The CADN is a reliable, valid, brief, quantifiable, and easily deployed assessment of swallowing in neurodegenerative disease. It is thus ideally suited for both clinical bedside assessment and future multicentre clinical trials in neurodegenerative disease.

Attenuated variants of Lesch-Nyhan disease

PubMed Central

Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Laróvere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

2010-01-01

Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. PMID:20176575

The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

PubMed

Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

2012-08-15

Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

Fabry disease in children: a federal screening programme in Russia.

PubMed

Namazova-Baranova, Leyla Seymurovna; Baranov, Alexander Alexandrovich; Pushkov, Aleksander Alekseevich; Savostyanov, Kirill Victorovich

2017-10-01

Our objective was to examine the prevalence of Fabry disease in Russian children with chronic pain in the distal limbs. This non-interventional, multi-centre study included children 2-18 years of age with chronic recurrent unilateral or bilateral pain, burning, or acroparesthesia in the hands or feet. The presence of Fabry disease was defined by abnormal alpha-galactosidase A activity in males or alpha-galactosidase gene (GLA) mutation in females. Among 214 patients (110 males), 84.1% had bilateral limb pain and 31.8% had unilateral limb pain recorded at some time point; 61 (28.5%) patients had a positive family history possibly associated with Fabry disease. Alpha-galactosidase A activity was within the normal range in all 109 of the male patients tested. One female patient had a GLA mutation (C937G > T) and alpha-galactosidase A activity within the normal range. We did not find definitive evidence of Fabry disease in these children with a history of chronic recurrent unilateral or bilateral limb pain or acroparesthesia. The presence of chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that key early signs and symptoms of Fabry disease are not specific to the disease. What is Known: • Signs and symptoms of Fabry disease are seen in children < 10 years of age; pain in the distal limbs is a common early symptom. What is New: • Fabry disease was not diagnosed in this population of Russian children with a history of chronic limb pain. • The presence of acroparesthesia or chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that these early symptoms of Fabry disease are not specific to the disease.

Endoscopic and histological pitfalls in the diagnosis of celiac disease: A multicentre study assessing the current practice.

PubMed

Rostami-Nejad, Mohammad; Villanacci, Vincenzo; Hogg-Kollars, Sabine; Volta, Umberto; Manenti, Stefania; Reza-Zali, Mohammad; Caio, Giacomo; Giovenali, Paolo; Barakauskiene, Ausrine; Kazenaite, Edita; Becheanu, Gabriel; Diculescu, Mircea; Pellegrino, Salvatore; Magazzù, Giuseppe; Casella, Giovanni; Di-Bella, Camillo; Decarli, Nicola; Biancalani, Mauro; Bassotti, Gabrio; Rostami, Kamran

2013-07-01

the diagnosis of celiac disease requires small bowel biopsies to identify the characteristic mucosal changes. The current biopsy practice among endoscopists for celiac disease is in most part unknown. The aim of this study was to compare the different diagnostic policies in various centers in their current practice. information from a total of 931 confirmed celiac disease patients was retrospectively obtained retrospectively from nine centers in European and Middle Eastern countries. The number of small-bowel biopsies obtained from the duodenal bulb and the second part of the duodenum was compared among different centers. the most frequent stage of mucosal changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and 15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For majority of cases, anemia was the most prevalent symptom (18.7%) followed by malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively. despite the evidence-based recommendations, this study revealed a poor compliance with major guidelines on diagnosis of celiac disease. We emphasize that taking adequate number of duodenal biopsies should be implemented for an accurate diagnosis and also for the exclusion of celiac disease.

Efficient, quality-assured data capture in operational research through innovative use of open-access technology

PubMed Central

Naik, B.; Guddemane, D. K.; Bhat, P.; Wilson, N.; Sreenivas, A. N.; Lauritsen, J. M.; Rieder, H. L.

2013-01-01

Ensuring quality of data during electronic data capture has been one of the most neglected components of operational research. Multicentre studies are also challenged with issues about logistics of travel, training, supervision, monitoring and troubleshooting support. Allocating resources to these issues can pose a significant bottleneck for operational research in resource-limited settings. In this article, we describe an innovative and efficient way of coordinating data capture in multicentre operational research using a combination of three open access technologies—EpiData for data capture, Dropbox for sharing files and TeamViewer for providing remote support. PMID:26392997

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

Multicentric Fibrosarcoma in a Cat and a Review of the Literature

PubMed Central

Harasen, G. L. G.

1984-01-01

A case of multicentric fibrosarcoma in a ten month old domestic short-haired cat is presented and discussed. Tumor tissue was found to involve the right distal forepaw, right shoulder area and a popliteal lymph node. This anaplastic neoplasm was concentrated primarily in subcutaneous tissues but also extended to muscle, bone and lung. The cat was found to be positive for feline leukemia virus by the ELISA test. Based on these findings, it is likely that the lesions in this case result from an interaction between the feline leukemia virus and feline sarcoma virus. ImagesFigures 1 and 2.Figure 3.Figure 4. PMID:17422403

Corruption and research.

PubMed

Luna, Florencia

1999-07-01

Last year there was a heated debate regarding clinical trials with AZT carried out in developing countries. AIDS vaccine trials also posed various dilemmas and ethical problems. In this paper I will consider the possibility of corruption in bioethics, and international multi-centre research will be taken as an example. International clinical trials will be seen from another perspective. I will try to show that the possibility of systemic corruption should be considered when designing an international multi-centre research trial which may involve countries in very different situations regarding corruption. I will analyze three different approaches to this problem and suggest some strategies regarding their capacity to exclude the possibility of corruption.

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting. Eudract No. 2010-023792-25 , registered on 4 November 2010.

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

PubMed

Gulley, James L; Rajan, Arun; Spigel, David R; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J L; Leach, Joseph; Edenfield, W Jeff; Wang, Ding; Grote, Hans Juergen; Heydebreck, Anja von; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

2017-05-01

Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing. Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8-18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression. Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Merck KGaA and Pfizer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results.

PubMed

Amaral, André F S; Coton, Sonia; Kato, Bernet; Tan, Wan C; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D; Buist, Sonia; Burney, Peter G J

2015-10-01

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. Copyright ©ERS 2015.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

PubMed Central

Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

2015-01-01

Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

PubMed

Hansen, M S; Klefter, O N; Julian, H O; Lynge Pedersen, A M; Heegaard, S

2017-10-01

Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D™ trial.

PubMed

Groop, Per-Henrik; Cooper, Mark E; Perkovic, Vlado; Sharma, Kumar; Schernthaner, Guntram; Haneda, Masakazu; Hocher, Berthold; Gordat, Maud; Cescutti, Jessica; Woerle, Hans-Juergen; von Eynatten, Maximilian

2015-11-01

Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D™), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5 mg or placebo in addition to their stable glucose-lowering background therapy for 24 weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24 weeks with α = 0.05. MARLINA-T2D™ is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease. © The Author(s) 2015.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Multicentre, Prospective Observational Study of Pegfilgrastim Primary Prophylaxis in Patients at High Risk of Febrile Neutropenia in Poland: PROFIL Study

PubMed Central

Jurczak, Wojciech; Kalinka-Warzocha, Ewa; Chmielowska, Ewa; Duchnowska, Renata; Wojciechowska-Lampka, Elzbieta

2015-01-01

Aim of the study PROFIL was a prospective observational study conducted to investigate physicians’ evaluation of febrile neutropenia (FN) risk and reasons for giving pegfilgrastim primary prophylaxis (PP) in routine clinical practice in Poland. Material and methods Adult cancer patients treated with chemotherapy (CT), assessed by investigators as having high overall FN risk, and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010. Investigators assessed FN risk of the CT regimen, individual risk factors, and overall FN risk, and were asked to provide the most important reasons for providing pegfilgrastim PP. Investigator-assessed CT FN risk was compared with guideline classification. Results Data were analysed from 1006 breast, ovarian, and lung cancer, and non-Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease; these were consistent across tumour types and treatment intent. The investigators generally assessed high CT FN risk in agreement with guideline classification. Febrile neutropenia occurred in 4% of patients, most commonly in HL, NHL, and patients with advanced disease. Conclusions High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Poland. PMID:26557762

Long-term efficacy of microbiology-driven periodontal laser-assisted therapy.

PubMed

Martelli, F S; Fanti, E; Rosati, C; Martelli, M; Bacci, G; Martelli, M L; Medico, E

2016-03-01

Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease.

European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO).

PubMed

Vojinovic, Jelena; Tincani, Angela; Sulli, Alberto; Soldano, Stefano; Andreoli, Laura; Dall'Ara, Francesca; Ionescu, Ruxandra; Pasalic, Katarina Simic; Balcune, Inete; Ferraz-Amaro, Ivan; Tlustochowicz, Małgorzata; Butrimiene, Irena; Punceviciene, Egle; Toroptsova, Natalia; Grazio, Simeon; Morovic-Vergles, Jadranka; Masaryk, Pavol; Otsa, Kati; Bernardes, Miguel; Boyadzhieva, Vladimira; Salaffi, Fausto; Cutolo, Maurizio

2017-05-01

To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO). This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA patients group. Negative correlations were also found in the cohort of enrolled RA patients between 25(OH)D serum concentrations and SRS (p=0.04), HRS (p=0.02) and GRS (p=0.02) domains of the D-PRO questionnaire. This first multicentre European survey add new evidences that vitamin D insufficiency/deficiency is frequent in RA patients with statistically significant differences among several countries. Vitamin D serum concentrations seem to correlate negatively and significantly with the D-PRO Global Risk Score, clinimetric indexes for quality of life, disease activity and disability in present cohort of RA European patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Adalimumab in dermatology

PubMed Central

Traczewski, Pawel; Rudnicka, Lidia

2008-01-01

Adalimumab is a biological agent, one of the tumour necrosis factor-alpha inhibitors. Pivotal studies evaluating its efficacy in plaque psoriasis (CHAMPION, REVEAL) and psoriatic arthritis (PsA) (ADEPT) were carried out in recent years. Adalimumab proved highly effective in psoriasis patients and in PsA patients previously unresponsive to nonsteroidal anti-inflammatory drugs. Results of smaller studies suggest therapy with the drug may be successful in psoriasis resistant to other biologics and PsA unresponsive to disease-modifying antirheumatic drugs. Adalimumab has also been shown to improve patients' quality of life significantly. Although they should be further extended as far as dermatological conditions are concerned, available data indicate adalimumab is safe and well tolerated. Numerous case reports featuring its off-label use suggest the drug could be helpful in treating hidradenitis suppurativa, pyoderma gangrenosum, Sweet's syndrome, cutaneous sarcoidosis, pemphigus, systemic vasculitides, multicentric reticulohistiocytosis and stomatitis. PMID:18754844

Adalimumab in dermatology.

PubMed

Traczewski, Pawel; Rudnicka, Lidia

2008-11-01

Adalimumab is a biological agent, one of the tumour necrosis factor-alpha inhibitors. Pivotal studies evaluating its efficacy in plaque psoriasis (CHAMPION, REVEAL) and psoriatic arthritis (PsA) (ADEPT) were carried out in recent years. Adalimumab proved highly effective in psoriasis patients and in PsA patients previously unresponsive to nonsteroidal anti-inflammatory drugs. Results of smaller studies suggest therapy with the drug may be successful in psoriasis resistant to other biologics and PsA unresponsive to disease-modifying antirheumatic drugs. Adalimumab has also been shown to improve patients' quality of life significantly. Although they should be further extended as far as dermatological conditions are concerned, available data indicate adalimumab is safe and well tolerated. Numerous case reports featuring its off-label use suggest the drug could be helpful in treating hidradenitis suppurativa, pyoderma gangrenosum, Sweet's syndrome, cutaneous sarcoidosis, pemphigus, systemic vasculitides, multicentric reticulohistiocytosis and stomatitis.

An integrated Diet Monitoring Solution for nutrigenomic research.

PubMed

Conti, Costanza; Rossi, Elena; Marceglia, Sara; Tauro, Vittorio; Rizzi, Federica; Lazzaroni, Monica; Barlassina, Cristina; Soldati, Laura; Cusi, Daniele

2015-01-01

The emergence of evidence pointing at diet as key risk factor for chronic diseases and at gene-diet interactions as key elements in the interplay between an individual genetic background and his/her lifestyle, pave the way for studies in nutrigenomics. Such studies need an integrated solution to collect, monitor and analyse a large set of data. In the frame of ATHENA, a European Commission FP7 project, we developed an integrated platform, called Dietary Monitoring Solution enabling the collection of phenotypic, genetic and lifestyle information, linked to a mHealth application tool. The data collection solution allows maintaining anonymized information and supports a number of features making it particularly suited for multicentre studies. The mHealth application was designed to translate the knowledge generated from research into a personalised prevention programme and to support the patient adherence to the programme.

Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial.

PubMed

Zhu, Andrew X; Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Poon, Ronnie; Pastorelli, Davide; Blanc, Jean-Frederic; Chung, Hyun Cheol; Baron, Ari D; Pfiffer, Tulio Eduardo Flesch; Okusaka, Takuji; Kubackova, Katerina; Trojan, Jorg; Sastre, Javier; Chau, Ian; Chang, Shao-Chun; Abada, Paolo B; Yang, Ling; Schwartz, Jonathan D; Kudo, Masatoshi

2015-07-01

VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. Eli Lilly and Co. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study.

PubMed

Walsh, Simon L F; Wells, Athol U; Desai, Sujal R; Poletti, Venerino; Piciucchi, Sara; Dubini, Alessandra; Nunes, Hilario; Valeyre, Dominique; Brillet, Pierre Y; Kambouchner, Marianne; Morais, António; Pereira, José M; Moura, Conceição Souto; Grutters, Jan C; van den Heuvel, Daniel A; van Es, Hendrik W; van Oosterhout, Matthijs F; Seldenrijk, Cornelis A; Bendstrup, Elisabeth; Rasmussen, Finn; Madsen, Line B; Gooptu, Bibek; Pomplun, Sabine; Taniguchi, Hiroyuki; Fukuoka, Junya; Johkoh, Takeshi; Nicholson, Andrew G; Sayer, Charlie; Edmunds, Lilian; Jacob, Joseph; Kokosi, Maria A; Myers, Jeffrey L; Flaherty, Kevin R; Hansell, David M

2016-07-01

Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. National Institute of Health Research, Imperial College London. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study.

PubMed

Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline

2014-01-01

To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.

Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study.

PubMed

Ferraù, Francesco; Romeo, P D; Puglisi, S; Ragonese, M; Torre, M L; Scaroni, C; Occhi, G; De Menis, E; Arnaldi, G; Trimarchi, F; Cannavò, S

2016-12-01

This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant.

Italian multicentre study on microbial environmental contamination in dental clinics: a pilot study.

PubMed

Pasquarella, Cesira; Veronesi, Licia; Castiglia, Paolo; Liguori, Giorgio; Montagna, Maria Teresa; Napoli, Christian; Rizzetto, Rolando; Torre, Ida; Masia, Maria Dolores; Di Onofrio, Valeria; Colucci, Maria Eugenia; Tinteri, Carola; Tanzi, Marialuisa

2010-09-01

The dental practice is associated with a high risk of infections, both for patients and healthcare operators, and the environment may play an important role in the transmission of infectious diseases. A microbiological environmental investigation was carried out in six dental clinics as a pilot study for a larger multicentre study that will be performed by the Italian SItI (Society of Hygiene, Preventive Medicine and Public Health) working group "Hygiene in Dentistry". Microbial contamination of water, air and surfaces was assessed in each clinic during the five working days of the week, before and during treatments. Air and surfaces were also examined at the end of the daily activity. A wide variation was found in microbial environmental contamination, both within the participating clinics and relative to the different sampling times. Microbial water contamination in Dental Unit Water Systems (DUWS) reached values of up to 26x10(4)cfu/mL (colony forming units per millilitre). P. aeruginosa was found in 33% of the sampled DUWS and Legionella spp. in 50%. A significant decrease in the Total Viable Count (TVC) was recorded during the activity. Microbial air contamination showed the highest levels during dental treatments and tended to decrease at the end of the working activity (p<0.05). Microbial buildup on surfaces increased significantly during the working hours. As these findings point out, research on microbial environmental contamination and the related risk factors in dental clinics should be expanded and should also be based on larger collections of data, in order to provide the essential knowledge aimed at targeted preventive interventions. Copyright 2010 Elsevier B.V. All rights reserved.

Innovative Telemonitoring Enhanced Care Programme for Chronic Heart Failure (ITEC-CHF) to improve guideline compliance and collaborative care: protocol of a multicentre randomised controlled trial

PubMed Central

Jayasena, Rajiv; Maiorana, Andrew; Dowling, Alison; Chen, Sheau Huey; Karunanithi, Mohan; Layland, Jamie; Edwards, Iain

2017-01-01

Introduction Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients’ compliance, and associated health and economic outcomes. Methods and analysis An open multicentre randomised controlled trial has been designed. Patients will be recruited and randomised to receive either ITEC-CHF (n=150) or usual care CHF (n=150) for at least 6 months. ITEC-CHF combines usual care and an additional telemonitoring service including remote weight monitoring, structured telephone support and nurse-led collaborative care. The primary outcomes are the compliance rates with the best-practice guidelines for daily weight monitoring. The secondary outcomes include the compliance with other guideline recommendations (health maintenance, medication, diet and exercise), health (health-related quality of life, risk factors, functional capacity and psychological states) and economic outcomes related to the use of healthcare resources such as hospital readmissions and general practitioner/emergency department visits. Ethics and dissemination The clinical trial has been approved by Peninsula Health Human Research Ethics Committee (HREC Reference: HREC/14/PH/27), Royal Perth Hospital Human Research Ethics Committee (Reference: 15-081) and the Curtin University Human Research Ethics Committee (Reference: HR 181/2014). We will disseminate the final results to the public via conferences and journal publications. A final study report will also be provided to the ethics committees. Trial registration number Registered with Australian New Zealand Clinical Trial Registry (ACTRN12614000916640). PMID:28993389

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

PubMed

Schellekens, M P J; van den Hurk, D G M; Prins, J B; Donders, A R T; Molema, J; Dekhuijzen, R; van der Drift, M A; Speckens, A E M

2017-12-01

Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own. Copyright © 2017 John Wiley & Sons, Ltd.

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial.

PubMed

Li, Yanping; Hu, Xiaoqi; Zhang, Qian; Liu, Ailing; Fang, Hongyun; Hao, Linan; Duan, Yifan; Xu, Haiquan; Shang, Xianwen; Ma, Jun; Xu, Guifa; Du, Lin; Li, Ying; Guo, Hongwei; Li, Tingyu; Ma, Guansheng

2010-05-02

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

Characterization and Multicentric Validation of a Common Standard for Toxoplasma gondii Detection Using Nucleic Acid Amplification Assays

PubMed Central

Varlet-Marie, Emmanuelle; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Filisetti, Denis; Pelloux, Hervé; Touafek, Fériel; Yera, Hélène

2014-01-01

The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community. High-quality written procedures were used for the production and qualification of this standard. Three independent batches of this standard, containing concentrations ranging from 104 to 0.01 T. gondii genome equivalents per PCR, were first assessed: the linear dynamic range was ≥6 log, the intra-assay coefficients of variation (CV) from a sample containing 10 T. gondii organisms per PCR were 0.3% to 0.42%, and the interassay CV over a 2-week period was 0.76% to 1.47%. A further assessment in eight diagnostic centers showed that the standard is stable, robust, and reliable. These lyophilized standards can easily be produced at a larger scale when needed and can be made widely available at the national level. To our knowledge, this is the first quality control assessment of a common standard which is usable both for self-evaluation in laboratories and for accurate quantification of parasitic loads in T. gondii prenatal infections. PMID:25187637

Characterization and multicentric validation of a common standard for Toxoplasma gondii detection using nucleic acid amplification assays.

PubMed

Varlet-Marie, Emmanuelle; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Filisetti, Denis; Pelloux, Hervé; Touafek, Fériel; Yera, Hélène; Bastien, Patrick

2014-11-01

The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community. High-quality written procedures were used for the production and qualification of this standard. Three independent batches of this standard, containing concentrations ranging from 10(4) to 0.01 T. gondii genome equivalents per PCR, were first assessed: the linear dynamic range was ≥ 6 log, the intra-assay coefficients of variation (CV) from a sample containing 10 T. gondii organisms per PCR were 0.3% to 0.42%, and the interassay CV over a 2-week period was 0.76% to 1.47%. A further assessment in eight diagnostic centers showed that the standard is stable, robust, and reliable. These lyophilized standards can easily be produced at a larger scale when needed and can be made widely available at the national level. To our knowledge, this is the first quality control assessment of a common standard which is usable both for self-evaluation in laboratories and for accurate quantification of parasitic loads in T. gondii prenatal infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Faecal occult blood testing screening for colorectal cancer and 'missed' interval cancers: are we ignoring the elephant in the room? Results of a multicentre study.

PubMed

George, A T; Aggarwal, S; Dharmavaram, S; Menon, A; Dube, M; Vogler, M; Field, A

2017-05-01

Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme. Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome. A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Multi-centre evaluation of mass spectrometric identification of anaerobic bacteria using the VITEK® MS system.

PubMed

Garner, O; Mochon, A; Branda, J; Burnham, C-A; Bythrow, M; Ferraro, M; Ginocchio, C; Jennemann, R; Manji, R; Procop, G W; Richter, S; Rychert, J; Sercia, L; Westblade, L; Lewinski, M

2014-04-01

Accurate and timely identification of anaerobic bacteria is critical to successful treatment. Classic phenotypic methods for identification require long turnaround times and can exhibit poor species level identification. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an identification method that can provide rapid identification of anaerobes. We present a multi-centre study assessing the clinical performance of the VITEK(®) MS in the identification of anaerobic bacteria. Five different test sites analysed a collection of 651 unique anaerobic isolates comprising 11 different genera. Multiple species were included for several of the genera. Briefly, anaerobic isolates were applied directly to a well of a target plate. Matrix solution (α-cyano-4-hydroxycinnamic acid) was added and allowed to dry. Mass spectra results were generated with the VITEK(®) MS, and the comparative spectral analysis and organism identification were determined using the VITEK(®) MS database 2.0. Results were confirmed by 16S rRNA gene sequencing. Of the 651 isolates analysed, 91.2% (594/651) exhibited the correct species identification. An additional eight isolates were correctly identified to genus level, raising the rate of identification to 92.5%. Genus-level identification consisted of Actinomyces, Bacteroides and Prevotella species. Fusobacterium nucleatum, Actinomyces neuii and Bacteroides uniformis were notable for an increased percentage of no-identification results compared with the other anaerobes tested. VITEK(®) MS identification of clinically relevant anaerobes is highly accurate and represents a dramatic improvement over other phenotypic methods in accuracy and turnaround time. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

PubMed Central

del Muro, X García; Marcuello, E; Gumá, J; Paz-Ares, L; Climent, M A; Carles, J; Parra, M Sánchez; Tisaire, J L; Maroto, P; Germá, J R

2002-01-01

A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m−2 and cisplatin 75 mg m−2 on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79–102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41–74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3–4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3–4 thrombocytopenia was rare (one patient). Other grade 3–4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation. British Journal of Cancer (2002) 86, 326–330. DOI: 10.1038/sj/bjc/6600121 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11875692

Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study

PubMed Central

Pascual, Sergi; Feimer, Jan; De Soyza, Anthony; Sauleda Roig, Jaume; Haughney, John; Padullés, Laura; Seoane, Beatriz; Rekeda, Ludmyla; Ribera, Anna; Chrystyn, Henry

2015-01-01

Background: The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). Aims: To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use. Methods: Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device. Results: Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively). Conclusions: Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. PMID:25927321

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study.

PubMed

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. UMIN000034701.

SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis.

PubMed

Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Cooper, Cindy L; Cross, Elizabeth; Maguire, Chin; Cantrill, Hannah; Alexander, John; McNamara, Paul S

2014-12-01

Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0-95, 95% CI: 0.75-1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76-1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. NCT01469845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Optimisation and validation of a remote monitoring system (Onco-TreC) for home-based management of oral anticancer therapies: an Italian multicentre feasibility study.

PubMed

Passardi, Alessandro; Rizzo, Mimma; Maines, Francesca; Tondini, Carlo; Zambelli, Alberto; Vespignani, Roberto; Andreis, Daniele; Massa, Ilaria; Dianti, Marco; Forti, Stefano; Piras, Enrico Maria; Eccher, Claudio

2017-05-29

Despite the growing number of oral agents available for cancer treatment, their efficacy may be reduced due to the lack of adherence, inappropriate adverse event self-management and arbitrary dose adjustment. The management of anticancer therapies could exponentially benefit from the introduction of mobile health technologies in a highly integrated electronic oncology system. We plan to customise and fine-tune an existing monitoring TreC platform used in different chronic diseases in the oncology setting. This project follows a multistep approach with two major purposes: 1. participatory design techniques driven by Health Literacy and Patient Reported Outcomes principles in order to adapt the system to the oncology setting involving patients and healthcare providers; 2. a prospective training-validation, interventional, non-pharmacological, multicentre study on a series of consecutive patients with cancer (20 and 60 patients in the training and validation steps, respectively) in order to assess system capability, usability and acceptability. The novel Onco-TreC 2.0 is expected to contribute to improving the adherence and safety of cancer care, promoting patient empowerment and patient-doctor communication. Ethical approval was obtained from the Independent Ethics Committees of the participating institutions (CEIIAV protocol Number 2549/2015; reference Number 1315-PU). Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. ClinicalTrials.gov (NCT02921724); (Pre-results). Other study ID Number: IRST100.18. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial.

PubMed

Diener, Markus K; Seiler, Christoph M; Rossion, Inga; Kleeff, Jörg; Glanemann, Matthias; Butturini, Giovanni; Tomazic, Ales; Bruns, Christiane J; Busch, Olivier R C; Farkas, Stefan; Belyaev, Orlin; Neoptolemos, John P; Halloran, Christopher; Keck, Tobias; Niedergethmann, Marco; Gellert, Klaus; Witzigmann, Helmut; Kollmar, Otto; Langer, Peter; Steger, Ulrich; Neudecker, Jens; Berrevoet, Frederik; Ganzera, Silke; Heiss, Markus M; Luntz, Steffen P; Bruckner, Thomas; Kieser, Meinhard; Büchler, Markus W

2011-04-30

The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. German Federal Ministry of Education and Research.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study

PubMed Central

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

Introduction The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. Methods and analysis This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. Ethics and dissemination This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). Discussion If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. Trial registration number UMIN000034701. PMID:29527318

Active LifestyLe Rehabilitation interventions in aging spinal cord injury (ALLRISC): a multicentre research program.

PubMed

van der Woude, L H V; de Groot, S; Postema, K; Bussmann, J B J; Janssen, T W J; Post, M W M

2013-06-01

With today's specialized medical care, life expectancy of persons with a spinal cord injury (SCI) has considerably improved. With increasing age and time since injury, many individuals with SCI, however, show a serious inactive lifestyle, associated with deconditioning and secondary health conditions (SHCs) (e.g. pressure sores, urinary and respiratory tract infections, osteoporosis, upper-extremity pain, obesity, diabetes, cardiovascular disease) and resulting in reduced participation and quality of life (QoL). Avoiding this downward spiral, is crucial. To understand possible deconditioning and SHCs in persons aging with a SCI in the context of active lifestyle, fitness, participation and QoL and to examine interventions that enhance active lifestyle, fitness, participation and QoL and help prevent some of the SHCs. A multicentre multidisciplinary research program (Active LifestyLe Rehabilitation Interventions in aging Spinal Cord injury, ALLRISC) in the setting of the long-standing Dutch SCI-rehabilitation clinical research network. ALLRISC is a four-study research program addressing inactive lifestyle, deconditioning, and SHCs and their associations in people aging with SCI. The program consists of a cross-sectional study (n = 300) and three randomized clinical trials. All studies share a focus on fitness, active lifestyle, SHCs and deconditioning and outcome measures on these and other (participation, QoL) domains. It is hypothesized that a self-management program, low-intensity wheelchair exercise and hybrid functional electrical stimulation-supported leg and handcycling are effective interventions to enhance active life style and fitness, help to prevent some of the important SHCs in chronic SCI and improve participation and QoL. ALLRISC aims to provide evidence-based preventive components of a rehabilitation aftercare system that preserves functioning in aging persons with SCI.

A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.

PubMed

Werner, Gerald S; Martin-Yuste, Victoria; Hildick-Smith, David; Boudou, Nicolas; Sianos, Georgios; Gelev, Valery; Rumoroso, Jose Ramon; Erglis, Andrejs; Christiansen, Evald Høj; Escaned, Javier; di Mario, Carlo; Hovasse, Thomas; Teruel, Luis; Bufe, Alexander; Lauer, Bernward; Bogaerts, Kris; Goicolea, Javier; Spratt, James C; Gershlick, Anthony H; Galassi, Alfredo R; Louvard, Yves

2018-05-02

The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. NCT01760083.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

PubMed

Celis-Morales, Carlos; Livingstone, Katherine M; Marsaux, Cyril F M; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Macready, Anna L; Fallaize, Rosalind; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Kolossa, Silvia; Hartwig, Kai; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Daly, E J; Akujobi, Victor; O'Riordan, Rick; Hoonhout, Jettie; Claassen, Arjan; Hoeller, Ulrich; Gundersen, Thomas E; Kaland, Siv E; Matthews, John N S; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Alfredo Martinez, J; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

2015-01-01

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

PubMed

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

Measuring outcome differences associated with STEMI screening and diagnostic performance: a multicentred retrospective cohort study protocol.

PubMed

Yiadom, Maame Yaa A B; Mumma, Bryn E; Baugh, Christopher W; Patterson, Brian W; Mills, Angela M; Salazar, Gilberto; Tanski, Mary; Jenkins, Cathy A; Vogus, Timothy J; Miller, Karen F; Jackson, Brittney E; Lehmann, Christoph U; Dorner, Stephen C; West, Jennifer L; Wang, Thomas J; Collins, Sean P; Dittus, Robert S; Bernard, Gordon R; Storrow, Alan B; Liu, Dandan

2018-05-03

Advances in ST-segment elevation myocardial infarction (STEMI) management have involved improving the clinical processes connecting patients with timely emergency cardiovascular care. Screening upon emergency department (ED) arrival for an early ECG to diagnose STEMI, however, is not optimal for all patients. In addition, the degree to which timely screening and diagnosis are associated with improved time to intervention and postpercutaneous coronary intervention outcomes, under more contemporary practice conditions, is not known. We present the methods for a retrospective multicentre cohort study anticipated to include 1220 patients across seven EDs to (1) evaluate the relationship between timely screening and diagnosis with treatment and postintervention clinical outcomes; (2) introduce novel measures for cross-facility performance comparisons of screening and diagnostic care team performance including: door-to-screening, door-to-diagnosis and door-to-catheterisation laboratory arrival times and (3) describe the use of electronic health record data in tandem with an existing disease registry. The completion of this study will provide critical feedback on the quality of screening and diagnostic performance within the contemporary STEMI care pathway that can be used to (1) improve emergency care delivery for patients with STEMI presenting to the ED, (2) present novel metrics for the comparison of screening and diagnostic care and (3) inform the development of screening and diagnostic support tools that could be translated to other care environments. We will disseminate our results via publication and quality performance data sharing with each site. Institutional ethics review approval was received prior to study initiation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study.

PubMed

2018-05-03

Gastrointestinal perforation is the most serious complication of typhoid fever, with a high disease burden in low-income countries. Reliable, prospective, contemporary surgical outcome data are scarce in these settings. This study aimed to investigate surgical outcomes following surgery for intestinal typhoid. Two multicentre, international prospective cohort studies of consecutive patients undergoing surgery for gastrointestinal typhoid perforation were conducted. Outcomes were measured at 30 days and included mortality, surgical site infection, organ space infection and reintervention rate. Multilevel logistic regression models were used to adjust for clinically plausible explanatory variables. Effect estimates are expressed as odds ratios (ORs) alongside their corresponding 95% confidence intervals. A total of 88 patients across the GlobalSurg 1 and GlobalSurg 2 studies were included, from 11 countries. Children comprised 38.6% (34/88) of included patients. Most patients (87/88) had intestinal perforation. The 30-day mortality rate was 9.1% (8/88), which was higher in children (14.7 vs. 5.6%). Surgical site infection was common, at 67.0% (59/88). Organ site infection was common, with 10.2% of patients affected. An ASA grade of III and above was a strong predictor of 30-day post-operative mortality, at the univariable level and following adjustment for explanatory variables (OR 15.82, 95% CI 1.53-163.57, p = 0.021). With high mortality and complication rates, outcomes from surgery for intestinal typhoid remain poor. Future studies in this area should focus on sustainable interventions which can reduce perioperative morbidity. At a policy level, improving these outcomes will require both surgical and public health system advances.

Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study.

PubMed

Xu, Lan-Ping; Wang, Shun-Qing; Wu, De-Pei; Wang, Jian-Min; Gao, Su-Jun; Jiang, Ming; Wang, Cun-Bang; Zhang, Xi; Liu, Qi-Fa; Xia, Ling-Hui; Wang, Xin; Huang, Xiao-Jun

2016-10-01

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes. © 2016 John Wiley & Sons Ltd.

Cohort profile: the German ClinSurv HIV project--a multicentre open clinical cohort study supplementing national HIV surveillance.

PubMed

Bätzing-Feigenbaum, J; Kollan, C; Kühne, A; Matysiak-Klose, D; Gunsenheimer-Bartmeyer, B; Hamouda, O

2011-05-01

New forms of HIV/AIDS therapy require new surveillance instruments to meet shifting public health demands. The Clinical Surveillance of HIV Disease (ClinSurv HIV) project was established in 1999 as a collaboration between major HIV treatment centres in Germany and the Robert Koch Institute (RKI). The project contributes to national HIV surveillance and focuses on the changing epidemiology of HIV/AIDS after the introduction of new therapies in 1995. ClinSurv HIV is designed as an open multicentre observational cohort study of HIV-infected patients. Anonymized data on diagnoses, treatment and laboratory parameters are collected in a standardized format. Data are currently sampled biannually via 11 centres specializing in HIV diagnosis and care within the legal framework of the German Protection against Infection Act [Infektionsschutzgesetz (IfSG)]. A total of 14874 patients were enrolled in the study by 30 June 2009. Of these, 10221 patients (68.7%) were enrolled after 1 January 1999 and 6006 patients (40.4%) were known to have been diagnosed as positive for HIV before 1999. Evaluation indicators, such as the number of newly enrolled patients per half-year period, loss to follow-up, completeness of data per case, availability of data per possible clinical contact, and internal quality control parameters, show a very stable evolution in the cohort, which although open, can be observed. Comparison with the national HIV surveillance data suggests a high degree of representativeness according to major demographic variables. Bearing in mind the obvious strengths and weaknesses discussed, the German ClinSurv HIV cohort provides a broad range of research opportunities in the field of HIV/AIDS both within Germany and in international collaborative research.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: a retrospective multicentre study.

PubMed

Bota, Simona; Sporea, Ioan; Peck-Radosavljevic, Markus; Sirli, Roxana; Tanaka, Hironori; Iijima, Hiroko; Saito, Hidetsugu; Ebinuma, Hirotoshi; Lupsor, Monica; Badea, Radu; Fierbinteanu-Braticevici, Carmen; Petrisor, Ana; Friedrich-Rust, Mireen; Sarrazin, Christoph; Takahashi, Hirokazu; Ono, Naofumi; Piscaglia, Fabio; Marinelli, Sara; D'Onofrio, Mirko; Gallotti, Anna; Salzl, Petra; Popescu, Alina; Danila, Mirela

2013-09-01

Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

Improvement of fatigue in patients with rheumatoid arthritis treated with biologics: relationship with sleep disorders, depression and clinical efficacy. A prospective, multicentre study.

PubMed

Genty, Marlène; Combe, Bernard; Kostine, Marie; Ardouin, Elodie; Morel, Jacques; Lukas, Cédric

2017-01-01

To assess predictive factors of improvement in related fatigue in rheumatoid arthritis (RA) patients newly receiving biologic therapy, and specifically the influence of the improvement of the quality of sleep. We conducted a multicentre prospective study in RA patients requiring initiation or change of biologic therapy. The improvement in fatigue, sleep disorders and depression was assessed respectively by the FACIT fatigue scale, Spiegel scale and Beck Depression Inventory at inclusion (M0) and 3 months (M3) after the beginning of treatment. Potential confounders were assessed and adjusted for. The association between evolution of fatigue and other characteristics were evaluated by univariate (χ2) then multivariate (logistic regression) analyses. We followed-up 99 patients. FACIT scores at M0 revealed frequently reported fatigue: 89%, high prevalence of sleep disorders: 95% and depression: 67%. Improvement of fatigue, sleep quality and depression was observed in 58.6%, 26.3% and 34.3% of cases, respectively. Significant factors associated with an improvement in fatigue at M3 were an elevated sedimentation rate at M0 (OR=5.7[2.0-16.0], p=0.001) and a favourable EULAR response at M3 (OR=4.8[1.6-14.8], p=0.006). Furthermore, a number of swollen joints > 5 at baseline (OR=0.3 [0.1-0.8]) and the use of psychotropic drugs (OR=0.2[0.04-0.9]) were predictive of an absence of improvement in fatigue. No significant association with the improvement in sleep disorders could be demonstrated. Fatigue in RA is improved by effective treatment, via decreasing disease activity. Improvement of sleep disorders is more likely a surrogate of therapeutic efficiency rather than an independent outcome.

A national registry for juvenile dermatomyositis and other paediatric idiopathic inflammatory myopathies: 10 years' experience; the Juvenile Dermatomyositis National (UK and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory Myopathies

PubMed Central

Martin, Neil; Krol, Petra; Smith, Sally; Murray, Kevin; Pilkington, Clarissa A.; Davidson, Joyce E.

2011-01-01

Objectives. The paediatric idiopathic inflammatory myopathies (IIMs) are a group of rare chronic inflammatory disorders of childhood, affecting muscle, skin and other organs. There is a severe lack of evidence base for current treatment protocols in juvenile myositis. The rarity of these conditions means that multicentre collaboration is vital to facilitate studies of pathogenesis, treatment and disease outcomes. We have established a national registry and repository for childhood IIM, which aims to improve knowledge, facilitate research and clinical trials, and ultimately to improve outcomes for these patients. Methods. A UK-wide network of centres and research group was established to contribute to the study. Standardized patient assessment, data collection forms and sample protocols were agreed. The Biobank includes collection of peripheral blood mononuclear cells, serum, genomic DNA and biopsy material. An independent steering committee was established to oversee the use of data/samples. Centre training was provided for patient assessment, data collection and entry. Results. Ten years after inception, the study has recruited 285 children, of which 258 have JDM or juvenile PM; 86% of the cases have contributed the biological samples. Serial sampling linked directly to the clinical database makes this a highly valuable resource. The study has been a platform for 20 sub-studies and attracted considerable funding support. Assessment of children with myositis in contributing centres has changed through participation in this study. Conclusions. This establishment of a multicentre registry and Biobank has facilitated research and contributed to progress in the management of a complex group of rare muscloskeletal conditions. PMID:20823094

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

A prospective multi-centric open clinical trial of homeopathy in diabetic distal symmetric polyneuropathy.

PubMed

Nayak, Chaturbhuja; Oberai, Praveen; Varanasi, Roja; Baig, Hafeezullah; Ch, Raveender; Reddy, G R C; Devi, Pratima; S, Bhubaneshwari; Singh, Vikram; Singh, V P; Singh, Hari; Shitanshu, Shashi Shekhar

2013-04-01

To evaluate homeopathic treatment in the management of diabetic distal symmetric polyneuropathy. A prospective multi-centric clinical observational study was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) (India) at its five institutes/units. Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months. Out of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analyzed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only. This study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Vulvar cancer in Tunisia: Epidemiological and clinicopathological features multicentric study.

PubMed

Kehila, Mehdi; Harabi, Souad; Mhiri, Raoudha; Touhami, Omar; Abouda, Hassine Saber; Khlifi, Abdeljalil; Hsairi, Mohamed; Chelli, Dalenda; Derbel, Mohamed; Kebaili, Sahbi; Boujelbane, Nadia; Chaabene, Kais; Chanoufi, Mohamed Badis

2017-06-01

To describe for the first time the epidemiologic and clinico-pathologic characteristics of vulvar cancer in Tunisia. Two parts are distinguished in this study: Part1: Multicentric retrospective study about the characteristics of all cancer cases diagnosed during a 17-years period (January 1998-December 2014) in three departments of Gynecology and Obstetrics: one in south Tunisia and two in the capital. Part 2: To determine the Incidence trend of invasive vulvar cancer in North Tunisia 1994-2009, on the basis of North Cancer Registry of Tunisia. A total of 76 cases of vulvar cancer were recorded. The median age at diagnosis was 65.4years and 86.9% of patients were more than 55years old. The symptomatology was dominated by vulvar pruritus in 48.7%. The average size of the tumor was 3.96cm. Stage III was the most frequent (53.7%) followed by stage II (28.3%). Only 10.4% of tumors were at stage I. The most common histologic type of vulvar malignancy was squamous cell carcinoma (SCC) (94.7%). Standardized incidence varied from 1.2/100 000 (1994) to 0.5/100 000 (2009). There was significant decrease of Standardized incidence (APC of -8.8% per year, 95% CI: -5.5%, -9.0%-p<0.001). Vulvar cancer in Tunisia is a rare disease, occurs mostly in elderly women, and is diagnosed at advanced stages. Our findings emphasize that a greater effort should be made to facilitate early diagnosis, as treatment in earlier stages is less extensive and potentially curative. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Treatment patterns, clinical outcomes and health care costs associated with HER2-positive breast cancer with central nervous system metastases: a French multicentre observational study.

PubMed

Baffert, Sandrine; Cottu, Paul; Kirova, Youlia M; Mercier, Florence; Simondi, Cécile; Bachelot, Thomas; Le Rhun, Emilie; Levy, Christelle; Gutierrez, Maya; Madranges, Nicolas; Moldovan, Cristian; Coudert, Bruno; Spaëth, Dominique; Serin, Daniel; Cotté, François-Emery; Benjamin, Laure; Maillard, Cathie; Laulhere-Vigneau, Sabine; Durand-Zaleski, Isabelle

2013-10-31

The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature.

PubMed

Deutschbein, Timo; Fassnacht, Martin; Weismann, Dirk; Reincke, Martin; Mann, Klaus; Petersenn, Stephan

2015-01-01

Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen). Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21-day intervals, with cyclophosphamide (750 mg/m(2) ), vincristine (1·4 mg/m(2) ) and dacarbazine (600 mg/m(2) ) on day 1, and dacarbazine only (600 mg/m(2) ) on day 2. The main outcome measures were best response during treatment and progression-free survival. Eight patients (4 males; median age 55·5 (range 31-77) years) with progressive disease underwent a median of 6 (range 3-11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression-free survival was 5·4 (range 2·5-26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression-free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events. Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed. © 2014 John Wiley & Sons Ltd.

[Respiratory infections, Down's syndrome and congenital heart disease: the CIVIC 21 study].

PubMed

Medrano López, C; García-Guereta Silva, L; Lirio Casero, J; García Pérez, J

2009-07-01

We compare hospitalisation rates for acute respiratory tract infection in children younger than 24 months with significant congenital heart disease without Down's syndrome with those with Down's syndrome with or without congenital heart disease. This was an epidemiological, multicentre (53 Spanish hospitals), observational and prospective study, from October 2006 to April 2007. A total of 1085 patients were followed-up, of which 806 did not have Down's syndrome and 279 with Down's syndrome: 135 with significant, 38 with non significant and 105 without congenital heart disease. A total of 147 patients (13.1%; 95% CI, 11.2-15.2%) required hospitalisation due to respiratory infection. Rates in patients without and with Down's syndrome were 11% vs 19.1%. In the Down's group, 26.3% had no significant, a 23% had significant and 11.4% had no congenital heart disease. The main diagnosis was bronchiolitis (59.4%). An infectious agent was found in 36.2% cases. The specific admission rate due to respiratory syncytial virus was 4.4%, with differences in children without vs with Down's syndrome (3.2% vs 7.8%). In the Down's patients we found rates of 15.8%, 9.3% and 3% in the non-significant, significant and no congenital heart disease. Immunoprophylaxis against respiratory syncytial virus rates were 83.4% vs 39.9% in no Down's versus Down's syndrome patients. No differences were found in hospital stay or the severity. Hospital admission rates due to respiratory infection, and specifically respiratory syncytial virus, were higher in the Down's patients, particularly in the group with no significant congenital heart disease and low immunoprophylaxis against respiratory syncytial virus.

Observer variability in the assessment of CT coronary angiography and coronary artery calcium score: substudy of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial

PubMed Central

Williams, Michelle C; Golay, Saroj K; Hunter, Amanda; Weir-McCall, Jonathan R; Mlynska, Lucja; Dweck, Marc R; Uren, Neal G; Reid, John H; Lewis, Steff C; Berry, Colin; van Beek, Edwin J R; Roditi, Giles; Newby, David E; Mirsadraee, Saeed

2015-01-01

Introduction Observer variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease. Methods We assessed 210 CTCAs from the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial for intraobserver and interobserver variability. Calcium score, coronary angiography and image quality were evaluated. Coronary artery disease was defined as none (<10%), mild (10–49%), moderate (50–70%) and severe (>70%) luminal stenosis and classified as no (<10%), non-obstructive (10–70%) or obstructive (>70%) coronary artery disease. Post-CTCA diagnosis of angina pectoris due to coronary heart disease was classified as yes, probable, unlikely or no. Results Patients had a mean body mass index of 29 (28, 30) kg/m2, heart rate of 58 (57, 60)/min and 62% were men. Intraobserver and interobserver agreements for the presence or absence of coronary artery disease were excellent (95% agreement, κ 0.884 (0.817 to 0.951) and good (91%, 0.791 (0.703 to 0.879)). Intraobserver and interobserver agreement for the presence or absence of angina pectoris due to coronary heart disease were excellent (93%, 0.842 (0.918 to 0.755) and good (86%, 0.701 (0.799 to 0.603)), respectively. Observer variability of calcium score was excellent for calcium scores below 1000. More segments were categorised as uninterpretable with 64-multidetector compared to 320-multidetector CTCA (10.1% vs 2.6%, p<0.001) but there was no difference in observer variability. Conclusions Multicentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease. Trial registration number NCT01149590. PMID:26019881

Vascular endothelial growth factor levels and rheumatic diseases of the elderly.

PubMed

Smets, Perrine; Devauchelle-Pensec, Valérie; Rouzaire, Paul-Olivier; Pereira, Bruno; Andre, Marc; Soubrier, Martin

2016-12-01

Increasing vascular endothelial growth factor (VEGF) has been reported in remitting symmetrical seronegative synovitis with pitting edema (RS3PE) syndrome, rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The aim of this study was to compare VEGF levels in patients over 60 years of age who have RS3PE, RA, PMR or GCA so as to determine whether elevated VEGF is specific for a rheumatic disease, the inflammation or edema that occurs with these pathological conditions. In this retrospective, multicentric study we assessed serum and plasma levels of VEGF in patients over 60 years of age with rheumatic diseases that were either de novo or of recent onset according to the initial clinical presentation, and we compared these patients with a control group. Serum and plasma VEGF levels were determined in 80 patients (5 with RS3PE, 13 with RA, 44 with PMR, and 18 with GCA) and 37 controls. Edema occurred in five patients with RS3PE, four with RA, and one with PMR, but not patients with GCA. Serum VEGF levels were significantly higher in individuals with rheumatic diseases (849 (405.5-1235.5) pg/ml) relative to the controls (484 (302-555) pg/ml) (p < 0.001). There were no significant differences between patients with RS3PE, RA, PMR, or GCA in terms of the VEGF serum levels (p = 0.60) or plasma levels (p = 0.57). Similarly, the occurrence of edema did not correlate with VEGF levels. VEGF increases in rheumatic diseases compared to a control group. This was not associated with specific rheumatic diseases or with edematous rheumatic diseases.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

PubMed

Gheorghe, C; Pascu, O; Iacob, R; Vadan, R; Iacob, S; Goldis, A; Tantau, M; Dumitru, E; Dobru, D; Miutescu, E; Saftoiu, A; Fraticiu, A; Tomescu, D; Gheorghe, L

2013-01-01

There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases. Celsius.

A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.

PubMed

Rossi, Emma C; Kowalski, Lynn D; Scalici, Jennifer; Cantrell, Leigh; Schuler, Kevin; Hanna, Rabbie K; Method, Michael; Ade, Melissa; Ivanova, Anastasia; Boggess, John F

2017-03-01

Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov, number NCT01673022 and is completed and closed. Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12%) patients had positive nodes, 36 of whom had at least one mapped sentinel lymph node. Nodal metastases were identified in the sentinel lymph nodes of 35 (97%) of these 36 patients, yielding a sensitivity to detect node-positive disease of 97·2% (95% CI 85·0-100), and a negative predictive value of 99·6% (97·9-100). The most common grade 3-4 adverse events or serious adverse events were postoperative neurological disorders (4 patients) and postoperative respiratory distress or failure (4 patients). 22 patients had serious adverse events, with one related to the study intervention: a ureteral injury incurred during sentinel-lymph-node dissection. Sentinel lymph nodes identified with indocyanine green have a high degree of diagnostic accuracy in detecting endometrial cancer metastases and can safely replace lymphadenectomy in the staging of endometrial cancer. Sentinel lymph node biopsy will not identify metastases in 3% of patients with node-positive disease, but has the potential to expose fewer patients to the morbidity of a complete lymphadenectomy. Indiana University Health, Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology. Copyright © 2017 Elsevier Ltd. All rights reserved.

A prospective multicentric international study on the surgical outcomes and patients' satisfaction rates of the 'sliding' technique for end-stage Peyronie's disease with severe shortening of the penis and erectile dysfunction.

PubMed

Rolle, Luigi; Falcone, Marco; Ceruti, Carlo; Timpano, Massimiliano; Sedigh, Omid; Ralph, David J; Kuehhas, Franklin; Oderda, Marco; Preto, Mirko; Sibona, Mattia; Gillo, Arianna; Garaffa, Giulio; Gontero, Paolo; Frea, Bruno

2016-05-01

To report the results from a prospective multicentric study of patients with Peyronie's disease (PD) treated with the 'sliding' technique (ST). From June 2010 to January 2014, 28 consecutive patients affected by stable PD with severe penile shortening and end-stage erectile dysfunction (ED) were enrolled in three European PD tertiary referral centres. The validated International Index of Erectile Function (IIEF) questionnaire, the Sexual Encounter Profile (SEP) Questions 2 and 3, and the Peyronie's disease questionnaire (PDQ) were completed preoperatively by all patients. At the follow-up visits (at 3, 6 and 12 months), the IIEF, the SEP Questions 2 and 3, the PDQ, and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) were completed. The outcome analysis was focused on penile length restoration, and intra- and postoperative complications classified according the Clavien-Dindo Classification. The mean (range) follow-up was 37 (9-60) months. A malleable penile prosthesis (PP) was implanted in seven patients, while an inflatable three-pieces PP was placed in the remainder. In the case of inflatable PP implantation, porcine small intestinal submucosa and acellular porcine dermal matrix were used to cover the tunical defects. While in patients undergoing malleable PP implantation, collagen-fibrin sponge was used. The mean operative time was 145 min in the inflatable PP group and 115 min in the malleable PP group. There were no intraoperative complications. Postoperative complications included profuse bleeding requiring a blood transfusion in one patient (3.5%) on anticoagulation therapy for a mechanical heart valve (Grade II) and PP infection requiring the removal of the device (7%) (Grade III). There were no late recurrences of the shaft deformation. The postoperative functional data showed a progressive improvement in the score of all questionnaires, peaking at 12 months postoperatively. The mean (range) penile lengthening was 3.2 (2.5-4) cm and no patient reported recurrence of the curvature. The present series suggests that, in the hands of experienced high-volume surgeons, penile length restoration with the use of the ST represents an effective option for end-stage PD associated with ED and severe shortening of the shaft. Larger series and longer follow-up will be required to fully establish the efficacy of this procedure. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial.

PubMed

Neuschwander-Tetri, Brent A; Loomba, Rohit; Sanyal, Arun J; Lavine, Joel E; Van Natta, Mark L; Abdelmalek, Manal F; Chalasani, Naga; Dasarathy, Srinivasan; Diehl, Anna Mae; Hameed, Bilal; Kowdley, Kris V; McCullough, Arthur; Terrault, Norah; Clark, Jeanne M; Tonascia, James; Brunt, Elizabeth M; Kleiner, David E; Doo, Edward

2015-03-14

The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis. We did a multicentre, double-blind, placebo-controlled, parallel group, randomised clinical trial at medical centres in the USA in patients with non-cirrhotic, non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally (25 mg daily) or placebo for 72 weeks. Patients were randomly assigned 1:1 using a computer-generated, centrally administered procedure, stratified by clinical centre and diabetes status. The primary outcome measure was improvement in centrally scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment. A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment (72 weeks) biopsies supported the decision to continue the trial (relative change in alanine aminotransferase -24%, 95% CI -45 to -3). A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid (p=0·0024) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients, but to continue the trial to obtain the 24-week post-treatment measures. Analyses were done by intention-to-treat. This trial was registered with ClinicalTrials.gov, number NCT01265498. Between March 16, 2011, and Dec 3, 2012, 141 patients were randomly assigned to receive obeticholic acid and 142 to placebo. 50 (45%) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 (21%) of 109 such patients in the placebo group (relative risk 1·9, 95% CI 1·3 to 2·8; p=0·0002). 33 (23%) of 141 patients in the obeticholic acid developed pruritus compared with nine (6%) of 142 in the placebo group. Obeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification. National Institute of Diabetes and Digestive and Kidney Diseases, Intercept Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of dosimetry audit in lung SBRT multi-centre clinical trials.

PubMed

Clark, Catharine H; Hurkmans, Coen W; Kry, Stephen F

2017-12-01

Stereotactic Body Radiotherapy (SBRT) in the lung is a challenging technique which requires high quality clinical trials to answer the un-resolved clinical questions. Quality assurance of these clinical trials not only ensures the safety of the treatment of the participating patients but also minimises the variation in treatment, thus allowing the lowest number of patient treatments to answer the trial question. This review addresses the role of dosimetry audits in the quality assurance process and considers what can be done to ensure the highest accuracy of dose calculation and delivery and it's assessment in multi-centre trials. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Standing up in multiple sclerosis (SUMS): protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

PubMed

Freeman, J A; Hendrie, W; Creanor, S; Jarrett, L; Barton, A; Green, C; Marsden, J; Rogers, E; Zajicek, J

2016-05-05

Multiple sclerosis (MS) is an incurable, unpredictable but typically progressive neurological condition. It is the most common cause of neurological disability in young adults. Within 15 years of diagnosis, approximately 50 % of affected people are unable to walk unaided, and over time an estimated 25 % depend on a wheelchair. Typically, people with such limited mobility are excluded from clinical trials. Severely impaired people with MS spend much of their day sitting, often with limited ability to change position. In response, secondary complications can occur including: muscle wasting, pain, reduced skin integrity, spasms, limb stiffness, constipation, and associated psychosocial problems such as depression and lowered self-esteem. Effective self-management strategies, which can be implemented relatively easily and cheaply within people's homes, are needed to improve or maintain mobility and reduce sedentary behaviour. However this is challenging, particularly in the latter stages of disease. Regular supported standing using standing frames is one potential option. SUMS is a pragmatic multi-centre randomised controlled trial evaluating use of Oswestry standing frames with blinded outcome assessment and full economic evaluation. Participants will be randomly allocated (1:1) to either a home-based, self-management standing programme (with advice and support) along with their usual care or to usual care alone. Those in the intervention group will be asked to stand for a minimum of 30 min three times weekly over 20 weeks. Each participant will be followed-up at 20 and 36 weeks post baseline. The primary clinical outcome is motor function, assessed using the Amended Motor Club Assessment. The primary economic endpoint is quality-adjusted life years. The secondary outcomes include measures of explanatory physical impairments, key clinical outcomes, and health-related quality of life. An embedded qualitative component will explore participant's and carer's experiences of the standing programme. This is the first large scale multi-centre trial to assess the clinical and cost effectiveness of a home based standing frame programme for people who are severely impaired by MS. If demonstrated to be effective and cost-effective, we will use this evidence to develop recommendations for a health service delivery model which could be implemented across the United Kingdom. ISRCTN69614598 DATE OF REGISTRATION: 3.2.16 (retrospectively registered).

Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Aka Aktürk, Ülkü; Görek Dilektaşlı, Aslı; Şengül, Aysun; Musaffa Salepçi, Banu; Oktay, Nuray; Düger, Mustafa; Arık Taşyıkan, Hale; Durmuş Koçak, Nagihan

2017-05-05

Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Multi-centre cross-sectional study. Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was 'no recommendation by doctors': 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p<0.001; pneumococcal vaccination p=0.06). There was no significant correlation with age, gender, smoking and severity of disease (p>0.05). Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001). Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients needs to be addressed.

Inter-observer agreement for Crohn's disease sub-phenotypes using the Montreal Classification: How good are we? A multi-centre Australasian study.

PubMed

Krishnaprasad, Krupa; Andrews, Jane M; Lawrance, Ian C; Florin, Timothy; Gearry, Richard B; Leong, Rupert W L; Mahy, Gillian; Bampton, Peter; Prosser, Ruth; Leach, Peta; Chitti, Laurie; Cock, Charles; Grafton, Rachel; Croft, Anthony R; Cooke, Sharon; Doecke, James D; Radford-Smith, Graham L

2012-04-01

Crohn's disease (CD) exhibits significant clinical heterogeneity. Classification systems attempt to describe this; however, their utility and reliability depends on inter-observer agreement (IOA). We therefore sought to evaluate IOA using the Montreal Classification (MC). De-identified clinical records of 35 CD patients from 6 Australian IBD centres were presented to 13 expert practitioners from 8 Australia and New Zealand Inflammatory Bowel Disease Consortium (ANZIBDC) centres. Practitioners classified the cases using MC and forwarded data for central blinded analysis. IOA on smoking and medications was also tested. Kappa statistics, with pre-specified outcomes of κ>0.8 excellent; 0.61-0.8 good; 0.41-0.6 moderate and ≤0.4 poor, were used. 97% of study cases had colonoscopy reports, however, only 31% had undergone a complete set of diagnostic investigations (colonoscopy, histology, SB imaging). At diagnosis, IOA was excellent for age, κ=0.84; good for disease location, κ=0.73; only moderate for upper GI disease (κ=0.57) and disease behaviour, κ=0.54; and good for the presence of perianal disease, κ=0.6. At last follow-up, IOA was good for location, κ=0.68; only moderate for upper GI disease (κ=0.43) and disease behaviour, κ=0.46; but excellent for the presence/absence of perianal disease, κ=0.88. IOA for immunosuppressant use ever and presence of stricture were both good (κ=0.79 and 0.64 respectively). IOA using MC is generally good; however some areas are less consistent than others. Omissions and inaccuracies reduce the value of clinical data when comparing cohorts across different centres, and may impair the ability to translate genetic discoveries into clinical practice. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Evaluation of learned helplessness, self-efficacy and disease activity, functional capacity and pain in Argentinian patients with rheumatoid arthritis.

PubMed

Vergara, F; Rosa, J; Orozco, C; Bertiller, E; Gallardo, M A; Bravo, M; Catay, E; Collado, V; Gómez, G; Sabelli, M; García, M V; Rosemffet, M G; Citera, G; Schneeberger, E E; Catoggio, L J; Soriano, E R

2017-01-01

To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.

Skin rash and arthritis a simplified appraisal of less common associations.

PubMed

Cozzi, A; Doria, A; Gisondi, P; Girolomoni, G

2014-06-01

Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information. © 2013 European Academy of Dermatology and Venereology.

Clinical characteristics and outcomes of HIV-associated immune complex kidney disease.

PubMed

Booth, John W; Hamzah, Lisa; Jose, Sophie; Horsfield, Catherine; O'Donnell, Patrick; McAdoo, Stephen; Kumar, Emil A; Turner-Stokes, Tabitha; Khatib, Nadia; Das, Partha; Naftalin, Claire; Mackie, Nicola; Kingdon, Ed; Williams, Debbie; Hendry, Bruce M; Sabin, Caroline; Jones, Rachael; Levy, Jeremy; Hilton, Rachel; Connolly, John; Post, Frank A

2016-12-01

The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease. In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies. Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria. These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Final data of an Italian multicentric survey about counseling for smoking cessation in patients with diagnosis of a respiratory disease.

PubMed

Capelletto, Enrica; Rapetti, Simonetta Grazia; Demichelis, Sara; Galetta, Domenico; Catino, Annamaria; Ricci, Donata; Moretti, Anna Maria; Bria, Emilio; Pilotto, Sara; Bruno, Arianna; Valmadre, Giuseppe; Bandelli, Gian Piero; Trisolini, Rocco; Gianetta, Martina; Pacchiana, Maria Vittoria; Vallone, Stefania; Novello, Silvia

2018-03-01

Smoking is the major risk factor for cancer and several respiratory diseases. Quitting smoking at any point of life may increase the effectiveness of treatments and improve prognosis of patients with any pulmonary disease, including lung cancer. However, few institutions in Europe offer to patients adequate counseling for smoking cessation. Aim of this study was to investigate the level of counseling for smoking cessation offered by healthcare professionals to patients and their appreciation towards the intervention itself. Between January 2013 and February 2016, 490 patients, diagnosed with a respiratory diseases, were prospectively evaluated with an anonymous survey developed by WALCE (Women Against Lung Cancer in Europe). The majority of patients enrolled (76%) declared to have stopped smoking after the diagnosis of a respiratory disease, 17% to smoke less, 7% to continue smoking. Patients who reported to have never received any counseling for smoking cessation were 38%. Almost 73% of the other patients reported a positive judgment about the quality of healthcare's intervention. Despite these favorable considerations, 83% of patients have disclosed they simply quit smoking overnight without help, 5% have used electronic cigarettes, 5% nicotine replacement treatments, 4% dedicated books, 3% have attended a referral clinic. Considering all the smoking-related side effects, greater efforts should be made in order to better support patients in smoking cessation. Smoking should be considered as a real physical disorder and similar surveys should be encouraged with the aim to fight the 'stigma' of smoking that still exists among patients. © 2017 John Wiley & Sons Ltd.

Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia.

PubMed

Lindvall, K; Colstrup, L; Wollter, I-M; Klemenz, G; Loogna, K; Grönhaug, S; Thykjaer, H

2006-01-01

It is well known that teenagers with chronic diseases have problems complying with their treatment. The aim of this study was to evaluate the patient's knowledge of haemophilia and his compliance to prophylactic treatment, and the age at which the patient took over the responsibility for his disease and to create educational material for teenagers and adolescents. This was a prospective multicentre study performed in Hemophilia Treatment Centres in Scandinavia. A total of 108 of 134 patients, between 13 and 25 years completed the questionnaire, a response rate of 80%. Eighty-three patients had a severe form of haemophilia, 24 patients in moderate form and one patient did not know the severity of his disease. Seventy-eight patients were on prophylactic treatment. The median age for starting prophylactic treatment was 3.0 years and the median age for the patient performing venepuncture was 11.6 years. Sixty-seven of 78 patients knew that the best time to give prophylactic treatment was in the morning. Even though the patients were on prophylactic treatment, 47 of 78 patients took additional treatment before sports activities. At a mean age of 14.1 years the patient himself had the responsibility for his disease and treatment. In the cohort of 108 patients, 73 were aware of their haemophilia heredity. This study shows a rather high degree of knowledge of haemophilia and compliance with treatment among the patients but it is of great importance for the nurse to continuously improve the patient's compliance and keep him aware of the benefit of regular treatment for his future well being.

European surveillance of emerging pathogens associated with canine infectious respiratory disease.

PubMed

Mitchell, Judy A; Cardwell, Jacqueline M; Leach, Heather; Walker, Caray A; Le Poder, Sophie; Decaro, Nicola; Rusvai, Miklos; Egberink, Herman; Rottier, Peter; Fernandez, Mireia; Fragkiadaki, Eirini; Shields, Shelly; Brownlie, Joe

2017-12-01

Canine infectious respiratory disease (CIRD) is a major cause of morbidity in dogs worldwide, and is associated with a number of new and emerging pathogens. In a large multi-centre European study the prevalences of four key emerging CIRD pathogens; canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), influenza A, and Mycoplasma cynos (M. cynos); were estimated, and risk factors for exposure, infection and clinical disease were investigated. CIRD affected 66% (381/572) of the dogs studied, including both pet and kennelled dogs. Disease occurrence and severity were significantly reduced in dogs vaccinated against classic CIRD agents, canine distemper virus (CDV), canine adenovirus 2 (CAV-2) and canine parainfluenza virus (CPIV), but substantial proportions (65.7%; 201/306) of vaccinated dogs remained affected. CRCoV and CnPnV were highly prevalent across the different dog populations, with overall seropositivity and detection rates of 47% and 7.7% for CRCoV, and 41.7% and 23.4% for CnPnV, respectively, and their presence was associated with increased occurrence and severity of clinical disease. Antibodies to CRCoV had a protective effect against CRCoV infection and more severe clinical signs of CIRD but antibodies to CnPnV did not. Involvement of M. cynos and influenza A in CIRD was less apparent. Despite 45% of dogs being seropositive for M. cynos, only 0.9% were PCR positive for M. cynos. Only 2.7% of dogs were seropositive for Influenza A, and none were positive by PCR. Copyright © 2017 Elsevier B.V. All rights reserved.

Classification of Chronic Obstructive Pulmonary Disease (COPD) according to the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017: Comparison with GOLD 2011.

PubMed

Marçôa, Raquel; Rodrigues, Daniela Marta; Dias, Margarida; Ladeira, Inês; Vaz, Ana Paula; Lima, Ricardo; Guimarães, Miguel

2018-02-01

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) project has been working to improve awareness, prevention and management of this disease. The aim of this study is to evaluate how COPD patients are reclassified by the 2017 GOLD system (versus GOLD 2011), to calculate the level of agreement between these two classifications in allocation to categories and to compare the performance of each classification to predict future exacerbations. Two-hundred COPD patients (>40 years, post bronchodilator forced expiratory volume in one second/forced vital capacity<0.7) followed in pulmonology consultation were recruited into this prospective multicentric study. Approximately half of the patients classified as GOLD D [2011] changed to GOLD B [2017]. The extent of agreement between GOLD 2011 and GOLD 2017 was moderate (Cohen's Kappa = 0.511; p < 0.001) and the ability to predict exacerbations was similar (69.7% and 67.6%, respectively). GOLD B [2017] exacerbated 17% more than GOLD B [2011] and had a lower percent predicted post bronchodilator forced expiratory volume in one second (FEV1). GOLD B [2017] turned to be the predominant category, more heterogeneous and with a higher risk of exacerbation versus GOLD B [2011]. Physicians should be cautious in assessing the GOLD B [2017] patients. The assessment of patients should always be personalized. More studies are needed to evaluate the impact of the 2017 reclassification in predicting outcomes such as future exacerbations and mortality.

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort].

PubMed

Duarte, Angela P; Marques, Cláudia D L; Bortoluzzo, Adriana B; Gonçalves, Célio R; da Silva, José Antonio Braga; Ximenes, Antonio Carlos; Bértolo, Manoel B; Ribeiro, Sandra Lúcia E; Keiserman, Mauro; Skare, Thelma L; Carneiro, Sueli; Menin, Rita; Azevedo, Valderilio F; Vieira, Walber P; Albuquerque, Elisa N; Bianchi, Washington A; Bonfiglioli, Rubens; Campanholo, Cristiano; Carvalho, Hellen M S; Costa, Izaias P; Kohem, Charles L; Leite, Nocy; Lima, Sonia A L; Meirelles, Eduardo S; Pereira, Ivânio A; Pinheiro, Marcelo M; Polito, Elizandra; Resende, Gustavo G; Rocha, Francisco Airton C; Santiago, Mittermayer B; Sauma, Maria de Fátima L C; Valim, Valéria; Sampaio-Barros, Percival D; Barros, Percival D Sampaio

2014-01-01

To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy treatment.

PubMed

Palmer, Antony L; Diez, Patricia; Gandon, Laura; Wynn-Jones, Andrea; Bownes, Peter; Lee, Chris; Aird, Edwin; Bidmead, Margaret; Lowe, Gerry; Bradley, David; Nisbet, Andrew

2015-02-01

To undertake the first multicentre fully 'end to end' dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. The mean difference between planned and measured dose at Point A was -0.6% for plastic applicators and -3.0% for metal applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. The concept of 'end to end' dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen].

PubMed

Zhou, Yun-feng; Wei, Yu-long; Zhang, Pu-lin; Gao, Shan; Ning, Guo-li; Zhang, Zhen-qiang; Hu, Bin; Wang, Dan-yi; Yan, Mei-rong; Liu, Wen-jun

2006-06-01

To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen. One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed. Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001). The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.

Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia

PubMed Central

Saraf, Santosh L.; Zhang, Xu; Kanias, Tamir; Lash, James P.; Molokie, Robert E.; Oza, Bharvi; Lai, Catherine; Rowe, Julie H.; Gowhari, Michel; Hassan, Johara; DeSimone, Joseph; Machado, Roberto F.; Gladwin, Mark T.; Little, Jane A.; Gordeuk, Victor R.

2014-01-01

Summary To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβ° thalassaemia patients from the University of Illinois at Chicago (UIC) and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (PHaSST) cohort. CKD was classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine dipstick with absent red blood cells on microscopy, was confirmed by enzyme-linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was observed in 36% and 20% of the patients, respectively. Pathway analysis in both cohorts indicated an independent association of lactate dehydrogenase with haemoglobinuria and, in turn, independent associations of haemoglobinuria and age with CKD (P<0.0001). After a median of 32 months of follow-up in the UIC cohort, haemoglobinuria was associated with progression of CKD (halving of estimated glomerular filtration rate or requirement for dialysis; Hazard ratio [HR] 13.9, 95% confidence interval [CI] 1.7-113.2, P=0.0012) and increasing albuminuria (HR 3.1, 95% CI: 1.3-7.7; logrank P=0.0035). In conclusion haemoglobinuria is common in SCA and is associated with CKD, consistent with a role for intravascular haemolysis in the pathogenesis of renal dysfunction in SCA. PMID:24329963

Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab.

PubMed

Nishimoto, Norihiro; Hashimoto, Jun; Miyasaka, Nobuyuki; Yamamoto, Kazuhiko; Kawai, Shinichi; Takeuchi, Tsutomu; Murata, Norikazu; van der Heijde, Désirée; Kishimoto, Tadamitsu

2007-09-01

To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA. In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method. Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively. Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.

Financial cost to institutions on patients waiting for gall bladder disease surgery.

PubMed

Waqas, Ahmed; Qasmi, Shahzad Ahmed; Kiani, Faran; Raza, Ahmed; Khan, Khizar Ishtiaque; Manzoor, Shazia

2014-01-01

The aim of this study was to determine the financial costs to institution on patients waiting for gall bladder disease surgery and suggest measures to reduce them. This multi-centre prospective descriptive survey was performed on all patients who underwent an elective cholecystectomy by three consultants at secondary care hospitals in Pakistan between Jan 2010 to Jan 2012. Data was collected on demographics, the duration of mean waiting time, specific indications and nature of disease for including the patients in the waiting list, details of emergency re-admissions while awaiting surgery, investigations done, treatment given and expenditures incurred on them during these episodes. A total of 185 patients underwent elective open cholecystectomy. The indications for listing the patients for surgery were biliary colic in 128 patients (69%), acute cholecystitis in 43 patients (23%), obstructive jaundice in 8 patients (4.5%) and acute pancreatitis in 6 patients (3.2%). 146 (78.9%) and 39 (21.1%) of patients were listed as outdoor electives and indoor emergencies respectively. Of the 185 patients, 54 patients (29.2%) were re-admitted. Financial costs in Pakistani rupees per episode of readmission were 23050 per episode in total and total money spent on all readmissions was Rs. 17,05,700/-. Financial costs on health care institutions due to readmissions in patients waiting for gall bladder disease surgery are high. Identifying patients at risk for these readmissions and offering them early laparoscopic cholecystectomy is very important.

Growth and nutritional status in children with chronic kidney disease on maintenance dialysis in Poland.

PubMed

Stańczyk, Małgorzata; Miklaszewska, Monika; Zachwieja, Katarzyna; Wierciński, Ryszard; Stankiewicz, Roman; Firszt-Adamczyk, Agnieszka; Zachwieja, Jacek; Borzęcka, Hanna; Zagożdżon, Ilona; Ziółkowska, Helena; Leszczyńska, Beata; Medyńska, Anna; Adamczyk, Piotr; Szczepańska, Maria; Tkaczyk, Marcin

2016-03-01

Despite vast availability of modern methods of treatment of chronic kidney disease and its complications, the short stature still is a major point of concern in adolescents with chronic kidney disease. The aim of the study was to assess changes in growth and nutritional status of Polish children on renal replacement therapy in the decade, 2004-2013. The study was designed as a cross-sectional analysis of anthropometric values and selected indices of growth status amongst children receiving dialysis in Poland between the years 2004 and 2013. Data were acquired during two different multicentre studies on hypertension in dialyzed children in Poland. Basic anthropometric parameters (body weight, body height/length, body mass index - BMI), dialysis adequacy and duration of RRT were assessed. The study showed that anthropometric parameters of children undergoing renal replacement therapy had not significantly changed in the last 10 years of observation. Children on RRT were still of short stature despite availability of modern methods of hormonal therapy and nutrition. Median of height z-score was -2.10 in 2004 and -2.19 in 2013. Expected clinical improvement in these measures was not proven. The cause of chronic kidney disease, method of dialysis, time on dialysis or dialysis adequacy did not influence the anthropometric parameters significantly in dialyzed children in Poland. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The real-world effectiveness of vedolizumab on intestinal and articular outcomes in inflammatory bowel diseases.

PubMed

Macaluso, Fabio Salvatore; Orlando, Rosalba; Fries, Walter; Scolaro, Mariangela; Magnano, Antonio; Pluchino, Dario; Cappello, Maria; Morreale, Gaetano Cristian; Siringo, Sebastiano; Privitera, Antonino Carlo; Ferracane, Concetta; Belluardo, Nunzio; Alberghina, Nadia; Ventimiglia, Marco; Rizzuto, Giulia; Renna, Sara; Cottone, Mario; Orlando, Ambrogio

2018-03-01

The effectiveness of vedolizumab in real-world practice is under evaluation, while its role in inflammatory bowel disease-associated spondyloarthritis is still unclear. To report real-world data about the effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22 weeks of treatment. Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a prospective multicentre observational study. 163 patients (84 with Crohn's disease and 79 with ulcerative colitis) were included. At week 10, a steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a steroid-free remission was obtained in 40.8% of patients. A response on articular symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%) patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%) patients at week 22. The only factor associated with articular response was the coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, p = 0.05; at week 22: OR 5.600, p = 0.08). Vedolizumab showed good effectiveness after 10 and 22 weeks of treatment. A subset of patients reported improvement also on articular symptoms, probably as a consequence of the concomitant control of gut inflammation. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

PubMed Central

Newton, Julia L; Frith, James; Powell, Danielle; Hackett, Kate; Wilton, Katharine; Bowman, Simon; Price, Elizabeth; Pease, Colin; Andrews, Jacqueline; Emery, Paul; Hunter, John; Gupta, Monica; Vadivelu, Saravanan; Giles, Ian; Isenberg, David; Lanyon, Peter; Jones, Adrian; Regan, Marian; Cooper, Annie; Moots, Robert; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; McLaren, John; Young-Min, Steven; Dasgupta, Bhaskar; Griffiths, Bridget; Lendrem, Dennis; Mitchell, Sheryl; Ng, Wan-Fai

2012-01-01

Objectives To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS. Methods Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis. Results COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009). Conclusions Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity. PMID:22562982

The management of refractory coeliac disease

PubMed Central

2013-01-01

A significant proportion of patients with coeliac disease are ‘nonresponsive’ to gluten withdrawal. Most cases of nonresponsive coeliac disease are due to persisting gluten ingestion. Refractory coeliac disease (RCD) is currently defined by persistent symptoms and signs of malabsorption after gluten exclusion for 12 months with ongoing intestinal villous atrophy. Primary (without initial response to diet) and secondary (relapse following response to diet) RCD is recognized. RCD is further classified as type I or type II based on the absence or presence of a population of aberrant intestinal lymphocytes. Quality of dietetic advice and support is fundamental, and lack of objective corroboration of gluten exclusion may result in over-identification of RCD I, particularly in those cases with persisting antibody responses. Over-reliance on lymphocyte clonality similarly may result in over-diagnosis of RCD II which requires careful quantification of aberrant lymphocyte populations. Management of RCD should be undertaken in specialist centres. It requires initial intensive dietary supervision, strict gluten exclusion and subsequent re-evaluation. There is currently insufficient evidence to recommend specific treatments. Steroids are often used in both RCD I and II (albeit with little objective evidence of benefit in RCD II), and azathioprine as steroid-sparing therapy in RCD I. There is growing evidence for the use of cladribine in RCD II with autologous stem cell transplantation in nonresponders, but this requires further multicentre evaluation. There remains considerable controversy regarding the diagnosis, treatment and surveillance of RCD: international consensus in these areas is urgently required to facilitate future therapeutic advances. PMID:23556127

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review.

PubMed

Grolez, G; Moreau, C; Danel-Brunaud, V; Delmaire, C; Lopes, R; Pradat, P F; El Mendili, M M; Defebvre, L; Devos, D

2016-08-27

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug's clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts. Hence, there is a need for more sensitive radiological biomarkers. Various sequences for magnetic resonance imaging (MRI) of the brain and spinal cord have may have value as surrogate biomarkers for use in future clinical trials. Here, we review the MRI findings in ALS, their clinical correlations, and their limitations and potential role as biomarkers. The PubMed database was screened to identify studies using MRI in ALS. We included general MRI studies with a control group and an ALS group and longitudinal studies even if a control group was lacking. A total of 116 studies were analysed with MRI data and clinical correlations. The most disease-sensitive MRI patterns are in motor regions but the brain is more broadly affected. Despite the existing MRI biomarkers, there is a need for large cohorts with long term MRI and clinical follow-up. MRI assessment could be improved by standardized MRI protocols with multicentre studies.

Do patients diagnosed with Alzheimer's disease benefit from a psycho-educational programme for family caregivers? A randomised controlled study.

PubMed

de Rotrou, Jocelyne; Cantegreil, Inge; Faucounau, Véronique; Wenisch, Emilie; Chausson, Catherine; Jegou, David; Grabar, Sophie; Rigaud, Anne-Sophie

2011-08-01

The Aide dans la Maladie d'Alzheimer (AIDMA) study was conducted to determine whether a psycho-educational programme (PEP) for primary caregivers in addition to standard anti-dementia drugs for patients improves caregivers' psychological condition and patients' activities of daily life. Multicentre randomised controlled intervention trial. One hundred and sixty-seven dyads 'patient-caregiver' were recruited from 15 French memory clinics and randomised in two parallel groups. The intervention group was offered the PEP in 12 group sessions for 3 months. The control group had usual care. Patients in both groups with mild to moderate Alzheimer's disease (AD) were diagnosed and treated with pharmacotherapy. Patients' primary efficacy variable was functional status assessed with the Disability Assessment Scale for Dementia (DAD) scale. Alzheimer Disease Assessment Scale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) were secondary criteria. Caregivers' first outcome measure was depressive symptoms assessed with the Montgomery and Asberg Depression Rating Scale (MADRS) scale. Zarit scale, Sense of Competence Questionnaire (SCQ) and Visual Analogue Scales (VAS) were secondary criteria. Assessment was done at baseline, 3 months (M3, end of intervention) and 6 months (M6). Patients' stabilisation was observed in both groups. In caregivers, significant improvement in disease understanding at M3 (p = 0.007) and M6 (p = 0.0001) and in ability to cope with care-recipients' disease at M6 (0.02) was evidenced. The PEP had no additional impact on patients but carers developed more effective disease understanding and ability of coping. Results support the idea that the PEP although improving caregivers' condition is not sufficient to improve patients' activities in daily life which requires additional individually tailored interventions provided by professionals. Copyright © 2010 John Wiley & Sons, Ltd.

Cognitive and Affective Changes in Mild to Moderate Alzheimer’s Disease Patients Undergoing Switch of Cholinesterase Inhibitors: A 6-Month Observational Study

PubMed Central

Spalletta, Gianfranco; Caltagirone, Carlo; Padovani, Alessandro; Sorbi, Sandro; Attar, Mahmood; Colombo, Delia; Cravello, Luca

2014-01-01

Patients with Alzheimer’s disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline), and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer’s disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled studies. PMID:24586603

Outcome of an education and home-based exercise programme for patients with ankylosing spondylitis: a nationwide randomized study.

PubMed

Rodríguez-Lozano, Carlos; Juanola, Xavier; Cruz-Martínez, Juan; Peña-Arrébola, Andrés; Mulero, Juan; Gratacós, Jordi; Collantes, Eduardo

2013-01-01

This study aims to assess the impact of a structured education and home exercise programme in daily practice patients with ankylosing spondylitis. A total of 756 patients with ankylosing spondylitis (72% males, mean age 45 years) participated in a 6-month prospective multicentre controlled study, 381 of whom were randomised to an education intervention (a 2-hour informative session about the disease and the implementation of a non-supervised physical activity programme at home) and 375 to standard care (controls). Main outcome measures included Bath Ankylosing Spondylitis Disease Activity and Functional Index (BASDAI, BASFI). Secondary outcome measures were 0-10 cm visual analog scale (VAS) for total pain, nocturnal pain and global disease activity and quality of life (ASQoL), knowledge of disease (self-evaluation ordinal scale) and daily exercise (diary card). At 6 months, the adjusted mean difference between control and educational groups for BASDAI was 0.32, 95% confidence interval (CI) 0.10-0.54, p=0.005, and for BASFI 0.31, 95%CI 0.12-0.51, p=0.002. Significant differences were found also in VAS for total pain, patient´s global assessment and in ASQoL. Patients in the education group increased their knowledge about the disease and its treatments significantly (p<0.001) and practised more regular exercise than controls (p<0.001). A structured education and home exercise programme for patients with ankylosing spondylitis in daily practice was feasible and helped to increase knowledge and exercise. Although statistically significant, the magnitudes of the clinical benefits in terms of disease activity and physical function were poor.

'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

PubMed

Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

2018-04-01

To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

[Profile of the informal carer associated with the clinical management of the Alzheimer's disease patient refractory to symptomatic treatment of the disease].

PubMed

Molinuevo, J L; Hernández, B

2011-11-01

Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as, time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers' quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (p<.0001) and final visit (p=.0001). Caregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p=.021). Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

Object-oriented business process analysis of the cooperative soft tissue sarcoma trial of the german society for paediatric oncology and haematology (GPOH).

PubMed

Weber, R; Knaup, P; Knietitg, R; Haux, R; Merzweiler, A; Mludek, V; Schilling, F H; Wiedemann, T

2001-01-01

The German Society for Paediatric Oncology and Haematology (GPOH) runs nation-wide multicentre clinical trials to improve the treatment of children suffering from malignant diseases. We want to provide methods and tools to support the centres of these trials in developing trial specific modules for the computer-based DOcumentation System for Paediatric Oncology (DOSPO). For this we carried out an object-oriented business process analysis for the Cooperative Soft Tissue Sarcoma Trial at the Olgahospital Stuttgart for Child and Adolescent Medicine. The result is a comprehensive business process model consisting of UML-diagrams and use case specifications. We recommend the object-oriented business process analysis as a method for the definition of requirements in information processing projects in the field of clinical trials in general. For this our model can serve as basis because it slightly can be adjusted to each type of clinical trial.